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Project acronym 2D-PnictoChem
Project Chemistry and Interface Control of Novel 2D-Pnictogen Nanomaterials
Researcher (PI) Gonzalo ABELLAN SAEZ
Host Institution (HI) UNIVERSITAT DE VALENCIA
Summary 2D-PnictoChem aims at exploring the Chemistry of a novel class of graphene-like 2D layered elemental materials of group 15, the pnictogens: P, As, Sb, and Bi. In the last few years, these materials have taken the field of Materials Science by storm since they can outperform and/or complement graphene properties. Their strongly layer-dependent unique properties range from semiconducting to metallic, including high carrier mobilities, tunable bandgaps, strong spin-orbit coupling or transparency. However, the Chemistry of pnictogens is still in its infancy, remaining largely unexplored. This is the niche that 2D-PnictoChem aims to fill. By mastering the interface chemistry, we will develop the assembly of 2Dpnictogens in complex hybrid heterostructures for the first time. Success will rely on a cross-disciplinary approach combining both Inorganic- and Organic Chemistry with Solid-state Physics, including: 1) Synthetizing and exfoliating high quality ultra-thin layer pnictogens, providing reliable access down to the monolayer limit. 2) Achieving their chemical functionalization via both non-covalent and covalent approaches in order to tailor at will their properties, decipher reactivity patterns and enable controlled doping avenues. 3) Developing hybrid architectures through a precise chemical control of the interface, in order to promote unprecedented access to novel heterostructures. 4) Exploring novel applications concepts achieving outstanding performances. These are all priorities in the European Union agenda aimed at securing an affordable, clean energy future by developing more efficient hybrid systems for batteries, electronic devices or applications in catalysis. The opportunity is unique to reduce Europe's dependence on external technology and the PI's background is ideally suited to tackle these objectives, counting as well on a multidisciplinary team of international collaborators.
2D-PnictoChem aims at exploring the Chemistry of a novel class of graphene-like 2D layered elemental materials of group 15, the pnictogens: P, As, Sb, and Bi. In the last few years, these materials have taken the field of Materials Science by storm since they can outperform and/or complement graphene properties. Their strongly layer-dependent unique properties range from semiconducting to metallic, including high carrier mobilities, tunable bandgaps, strong spin-orbit coupling or transparency. However, the Chemistry of pnictogens is still in its infancy, remaining largely unexplored. This is the niche that 2D-PnictoChem aims to fill. By mastering the interface chemistry, we will develop the assembly of 2Dpnictogens in complex hybrid heterostructures for the first time. Success will rely on a cross-disciplinary approach combining both Inorganic- and Organic Chemistry with Solid-state Physics, including: 1) Synthetizing and exfoliating high quality ultra-thin layer pnictogens, providing reliable access down to the monolayer limit. 2) Achieving their chemical functionalization via both non-covalent and covalent approaches in order to tailor at will their properties, decipher reactivity patterns and enable controlled doping avenues. 3) Developing hybrid architectures through a precise chemical control of the interface, in order to promote unprecedented access to novel heterostructures. 4) Exploring novel applications concepts achieving outstanding performances. These are all priorities in the European Union agenda aimed at securing an affordable, clean energy future by developing more efficient hybrid systems for batteries, electronic devices or applications in catalysis. The opportunity is unique to reduce Europe's dependence on external technology and the PI's background is ideally suited to tackle these objectives, counting as well on a multidisciplinary team of international collaborators.
Project acronym 2DMATER
Project Controlled Synthesis of Two-Dimensional Nanomaterials for Energy Storage and Conversion
Researcher (PI) Xinliang Feng
Host Institution (HI) TECHNISCHE UNIVERSITAET DRESDEN
Summary "Two-dimensional (2D) nanosheets, which possess a high degree of anisotropy with nanoscale thickness and infinite length in other dimensions, hold enormous promise as a novel class of ultrathin 2D nanomaterials with various unique functionalities and properties, and exhibit great potential in energy storage and conversion systems that are substantially different from their respective 3D bulk forms. Here I propose a strategy for the synthesis and processing of various 2D nanosheets across a broad range of inorganic, organic and polymeric materials with molecular-level or thin thickness through both the top-down exfoliation of layered materials and the bottom-up assembly of available molecular building blocks. Further, I aim to develop the synthesis of various 2D-nanosheet based composite materials with thickness of less than 100 nm and the assembly of 2D nanosheets into novel hierarchal superstrucutures (like aerogels, spheres, porous particles, nanotubes, multi-layer films). The structural features of these 2D nanomaterials will be controllably tailored by both the used layered precursors and processing methodologies. The consequence is that I will apply and combine defined functional components as well as assembly protocols to create novel 2D nanomaterials for specific purposes in energy storage and conversion systems. Their unique characters will include the good electrical conductivity, excellent mechanical flexibility, high surface area, high chemical stability, fast electron transport and ion diffusion etc. Applications will be mainly demonstrated for the construction of lithium ion batteries (anode and cathode), supercapacitors (symmetric and asymmetric) and fuel cells. As the key achievements, I expect to establish the delineation of reliable structure-property relationships and improved device performance of 2D nanomaterials."
"Two-dimensional (2D) nanosheets, which possess a high degree of anisotropy with nanoscale thickness and infinite length in other dimensions, hold enormous promise as a novel class of ultrathin 2D nanomaterials with various unique functionalities and properties, and exhibit great potential in energy storage and conversion systems that are substantially different from their respective 3D bulk forms. Here I propose a strategy for the synthesis and processing of various 2D nanosheets across a broad range of inorganic, organic and polymeric materials with molecular-level or thin thickness through both the top-down exfoliation of layered materials and the bottom-up assembly of available molecular building blocks. Further, I aim to develop the synthesis of various 2D-nanosheet based composite materials with thickness of less than 100 nm and the assembly of 2D nanosheets into novel hierarchal superstrucutures (like aerogels, spheres, porous particles, nanotubes, multi-layer films). The structural features of these 2D nanomaterials will be controllably tailored by both the used layered precursors and processing methodologies. The consequence is that I will apply and combine defined functional components as well as assembly protocols to create novel 2D nanomaterials for specific purposes in energy storage and conversion systems. Their unique characters will include the good electrical conductivity, excellent mechanical flexibility, high surface area, high chemical stability, fast electron transport and ion diffusion etc. Applications will be mainly demonstrated for the construction of lithium ion batteries (anode and cathode), supercapacitors (symmetric and asymmetric) and fuel cells. As the key achievements, I expect to establish the delineation of reliable structure-property relationships and improved device performance of 2D nanomaterials."
Project acronym 2O2ACTIVATION
Project Development of Direct Dehydrogenative Couplings mediated by Dioxygen
Researcher (PI) Frederic William Patureau
Host Institution (HI) RHEINISCH-WESTFAELISCHE TECHNISCHE HOCHSCHULE AACHEN
Summary The field of C-H bond activation has evolved at an exponential pace in the last 15 years. What appeals most in those novel synthetic techniques is clear: they bypass the pre-activation steps usually required in traditional cross-coupling chemistry by directly metalating C-H bonds. Many C-H bond functionalizations today however, rely on poorly atom and step efficient oxidants, leading to significant and costly chemical waste, thereby seriously undermining the overall sustainability of those methods. As restrictions in sustainability regulations will further increase, and the cost of certain chemical commodities will rise, atom efficiency in organic synthesis remains a top priority for research. The aim of 2O2ACTIVATION is to develop novel technologies utilizing O2 as sole terminal oxidant in order to allow useful, extremely sustainable, thermodynamically challenging, dehydrogenative C-N and C-O bond forming coupling reactions. However, the moderate reactivity of O2 towards many catalysts constitutes a major challenge. 2O2ACTIVATION will pioneer the design of new catalysts based on the ultra-simple propene motive, capable of direct activation of O2 for C-H activation based cross-couplings. The project is divided into 3 major lines: O2 activation using propene and its analogues (propenoids), 1) without metal or halide, 2) with hypervalent halide catalysis, 3) with metal catalyzed C-H activation. The philosophy of 2O2ACTIVATION is to focus C-H functionalization method development on the oxidative event. Consequently, 2O2ACTIVATION breakthroughs will dramatically shortcut synthetic routes through the use of inactivated, unprotected, and readily available building blocks; and thus should be easily scalable. This will lead to a strong decrease in the costs related to the production of many essential chemicals, while preserving the environment (water as terminal by-product). The resulting novels coupling methods will thus have a lasting impact on the chemical industry.
The field of C-H bond activation has evolved at an exponential pace in the last 15 years. What appeals most in those novel synthetic techniques is clear: they bypass the pre-activation steps usually required in traditional cross-coupling chemistry by directly metalating C-H bonds. Many C-H bond functionalizations today however, rely on poorly atom and step efficient oxidants, leading to significant and costly chemical waste, thereby seriously undermining the overall sustainability of those methods. As restrictions in sustainability regulations will further increase, and the cost of certain chemical commodities will rise, atom efficiency in organic synthesis remains a top priority for research. The aim of 2O2ACTIVATION is to develop novel technologies utilizing O2 as sole terminal oxidant in order to allow useful, extremely sustainable, thermodynamically challenging, dehydrogenative C-N and C-O bond forming coupling reactions. However, the moderate reactivity of O2 towards many catalysts constitutes a major challenge. 2O2ACTIVATION will pioneer the design of new catalysts based on the ultra-simple propene motive, capable of direct activation of O2 for C-H activation based cross-couplings. The project is divided into 3 major lines: O2 activation using propene and its analogues (propenoids), 1) without metal or halide, 2) with hypervalent halide catalysis, 3) with metal catalyzed C-H activation. The philosophy of 2O2ACTIVATION is to focus C-H functionalization method development on the oxidative event. Consequently, 2O2ACTIVATION breakthroughs will dramatically shortcut synthetic routes through the use of inactivated, unprotected, and readily available building blocks; and thus should be easily scalable. This will lead to a strong decrease in the costs related to the production of many essential chemicals, while preserving the environment (water as terminal by-product). The resulting novels coupling methods will thus have a lasting impact on the chemical industry.
Project acronym 3D-FNPWriting
Project Unprecedented spatial control of porosity and functionality in nanoporous membranes through 3D printing and microscopy for polymer writing
Researcher (PI) Annette ANDRIEU-BRUNSEN
Host Institution (HI) TECHNISCHE UNIVERSITAT DARMSTADT
Summary Membranes are key materials in our life. Nature offers high performance membranes relying on a parallel local regulation of nanopore structure, functional placement, membrane composition and architecture. Existing technological membranes are key materials in separation, recycling, sensing, energy conversion, being essential components for a sustainable future. But their performance is far away from their natural counterparts. One reason for this performance gap is the lack of 3D nanolocal control in membrane design. This applies to each individual nanopore but as well to the membrane architecture. This proposal aims to implement 3D printing (additive manufacturing, top down) and complex near-field and total internal reflection (TIR) high resolution microscopy induced polymer writing (bottom up) to nanolocally control in hierarchical nanoporous membranes spatially and independent of each other: porosity, pore functionalization, membrane architecture, composition. This disruptive technology platform will make accessible to date unachieved, highly accurate asymmetric nanopores and multifunctional, hierarchical membrane architecture/ composition and thus highly selective, directed, transport with tuneable rates. 3D-FNPWriting will demonstrate this for the increasing class of metal nanoparticle/ salt pollutants aiming for tuneable, selective, directed transport based monitoring and recycling instead of size-based filtration, accumulation into sewerage and distribution into nature. Specifically, the potential of this disruptive technology with respect to transport design will be demonstrated for a) a 3D-printed in-situ functionalized nanoporous fiber architecture and b) a printed, nanolocally near-field and TIR-microscopy polymer functionalized membrane representing a thin separation layer. This will open systematic understanding of nanolocal functional control on transport and new perspectives in water/ energy management for future smart industry/ homes.
Membranes are key materials in our life. Nature offers high performance membranes relying on a parallel local regulation of nanopore structure, functional placement, membrane composition and architecture. Existing technological membranes are key materials in separation, recycling, sensing, energy conversion, being essential components for a sustainable future. But their performance is far away from their natural counterparts. One reason for this performance gap is the lack of 3D nanolocal control in membrane design. This applies to each individual nanopore but as well to the membrane architecture. This proposal aims to implement 3D printing (additive manufacturing, top down) and complex near-field and total internal reflection (TIR) high resolution microscopy induced polymer writing (bottom up) to nanolocally control in hierarchical nanoporous membranes spatially and independent of each other: porosity, pore functionalization, membrane architecture, composition. This disruptive technology platform will make accessible to date unachieved, highly accurate asymmetric nanopores and multifunctional, hierarchical membrane architecture/ composition and thus highly selective, directed, transport with tuneable rates. 3D-FNPWriting will demonstrate this for the increasing class of metal nanoparticle/ salt pollutants aiming for tuneable, selective, directed transport based monitoring and recycling instead of size-based filtration, accumulation into sewerage and distribution into nature. Specifically, the potential of this disruptive technology with respect to transport design will be demonstrated for a) a 3D-printed in-situ functionalized nanoporous fiber architecture and b) a printed, nanolocally near-field and TIR-microscopy polymer functionalized membrane representing a thin separation layer. This will open systematic understanding of nanolocal functional control on transport and new perspectives in water/ energy management for future smart industry/ homes.
Project acronym 3DScavengers
Project Three-dimensional nanoscale design for the all-in-one solution to environmental multisource energy scavenging
Researcher (PI) Ana Isabel BORRAS MARTOS
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Summary Imagine a technology for powering your smart devices by recovering energy from lights in your office, the random movements of your body while reading these lines or from small changes in temperature when you breathe or go out for a walk. This very technology will provide energy for wireless sensor networks monitoring the air in your city or the structural stability of buildings and large constructions remotely and sustainably, avoiding battery recharging or even replacing them. These are the challenges in micro energy harvesting from (local) ambient sources. Kinetic, thermal and solar energies are ubiquitous at our surroundings under diverse forms, but their relatively low intensity and intermittent availability limit their potential recovery by microscale devices. These restrictions call for multi-source energy harvesters working under two principles: 1) combining different single-source harvesters in one device, or 2) using multifunctional materials capable of simultaneously converting various energy sources into electricity. In 1), efficiency per unit volume can decrease compared to the individual counterparts; in 2), materials as semiconductors, polymeric and oxide ferroelectrics and hybrid perovskites may act as multisource harvesters but huge advances are required to optimize their functionalities and sustainable fabrication at large scale. I propose to fill the gap between these approaches offering an all-in-one solution to multisource energy scavenging, based on the nanoscale design of multifunctional three-dimensional materials. The demonstration of an industrially scalable one-reactor plasma/vacuum method will be crucial to integrate hybrid-scavenging components and to provide 3DScavengers materials with tailored microstructure-enhanced performance. My ultimate goal is to build nanoarchitectures for simultaneous and enhanced individual scavenging applying photovoltaic, piezo- and pyro-electric effects, minimizing the environmental cost of their synthesis
Imagine a technology for powering your smart devices by recovering energy from lights in your office, the random movements of your body while reading these lines or from small changes in temperature when you breathe or go out for a walk. This very technology will provide energy for wireless sensor networks monitoring the air in your city or the structural stability of buildings and large constructions remotely and sustainably, avoiding battery recharging or even replacing them. These are the challenges in micro energy harvesting from (local) ambient sources. Kinetic, thermal and solar energies are ubiquitous at our surroundings under diverse forms, but their relatively low intensity and intermittent availability limit their potential recovery by microscale devices. These restrictions call for multi-source energy harvesters working under two principles: 1) combining different single-source harvesters in one device, or 2) using multifunctional materials capable of simultaneously converting various energy sources into electricity. In 1), efficiency per unit volume can decrease compared to the individual counterparts; in 2), materials as semiconductors, polymeric and oxide ferroelectrics and hybrid perovskites may act as multisource harvesters but huge advances are required to optimize their functionalities and sustainable fabrication at large scale. I propose to fill the gap between these approaches offering an all-in-one solution to multisource energy scavenging, based on the nanoscale design of multifunctional three-dimensional materials. The demonstration of an industrially scalable one-reactor plasma/vacuum method will be crucial to integrate hybrid-scavenging components and to provide 3DScavengers materials with tailored microstructure-enhanced performance. My ultimate goal is to build nanoarchitectures for simultaneous and enhanced individual scavenging applying photovoltaic, piezo- and pyro-electric effects, minimizing the environmental cost of their synthesis
Project acronym 4DBIOSERS
Project Four-Dimensional Monitoring of Tumour Growth by Surface Enhanced Raman Scattering
Researcher (PI) Luis LIZ-MARZAN
Host Institution (HI) ASOCIACION CENTRO DE INVESTIGACION COOPERATIVA EN BIOMATERIALES- CIC biomaGUNE
Summary Optical bioimaging is limited by visible light penetration depth and stability of fluorescent dyes over extended periods of time. Surface enhanced Raman scattering (SERS) offers the possibility to overcome these drawbacks, through SERS-encoded nanoparticle tags, which can be excited with near-IR light (within the biological transparency window), providing high intensity, stable, multiplexed signals. SERS can also be used to monitor relevant bioanalytes within cells and tissues, during the development of diseases, such as tumours. In 4DBIOSERS we shall combine both capabilities of SERS, to go well beyond the current state of the art, by building three-dimensional scaffolds that support tissue (tumour) growth within a controlled environment, so that not only the fate of each (SERS-labelled) cell within the tumour can be monitored in real time (thus adding a fourth dimension to SERS bioimaging), but also recording the release of tumour metabolites and other indicators of cellular activity. Although 4DBIOSERS can be applied to a variety of diseases, we shall focus on cancer, melanoma and breast cancer in particular, as these are readily accessible by optical methods. We aim at acquiring a better understanding of tumour growth and dynamics, while avoiding animal experimentation. 3D printing will be used to generate hybrid scaffolds where tumour and healthy cells will be co-incubated to simulate a more realistic environment, thus going well beyond the potential of 2D cell cultures. Each cell type will be encoded with ultra-bright SERS tags, so that real-time monitoring can be achieved by confocal SERS microscopy. Tumour development will be correlated with simultaneous detection of various cancer biomarkers, during standard conditions and upon addition of selected drugs. The scope of 4DBIOSERS is multidisciplinary, as it involves the design of high-end nanocomposites, development of 3D cell culture models and optimization of emerging SERS tomography methods.
Optical bioimaging is limited by visible light penetration depth and stability of fluorescent dyes over extended periods of time. Surface enhanced Raman scattering (SERS) offers the possibility to overcome these drawbacks, through SERS-encoded nanoparticle tags, which can be excited with near-IR light (within the biological transparency window), providing high intensity, stable, multiplexed signals. SERS can also be used to monitor relevant bioanalytes within cells and tissues, during the development of diseases, such as tumours. In 4DBIOSERS we shall combine both capabilities of SERS, to go well beyond the current state of the art, by building three-dimensional scaffolds that support tissue (tumour) growth within a controlled environment, so that not only the fate of each (SERS-labelled) cell within the tumour can be monitored in real time (thus adding a fourth dimension to SERS bioimaging), but also recording the release of tumour metabolites and other indicators of cellular activity. Although 4DBIOSERS can be applied to a variety of diseases, we shall focus on cancer, melanoma and breast cancer in particular, as these are readily accessible by optical methods. We aim at acquiring a better understanding of tumour growth and dynamics, while avoiding animal experimentation. 3D printing will be used to generate hybrid scaffolds where tumour and healthy cells will be co-incubated to simulate a more realistic environment, thus going well beyond the potential of 2D cell cultures. Each cell type will be encoded with ultra-bright SERS tags, so that real-time monitoring can be achieved by confocal SERS microscopy. Tumour development will be correlated with simultaneous detection of various cancer biomarkers, during standard conditions and upon addition of selected drugs. The scope of 4DBIOSERS is multidisciplinary, as it involves the design of high-end nanocomposites, development of 3D cell culture models and optimization of emerging SERS tomography methods.
Project acronym A2F2
Project Beyond Biopolymers: Protein-Sized Aromatic Amide Functional Foldamers
Researcher (PI) Ivan Huc
Summary Nature has evolved ultimate chemical functions based on controlling and altering conformation of its molecular machinery. Prominent examples include enzyme catalysis and information storage/duplication in nucleic acids. These achievements are based on large and complex yet remarkably defined structures obtained through folding of polymeric chains and a subtle interplay of non-covalent forces. Nature uses a limited set of building blocks – e.g. twenty amino-acids and four nucleobases – with specific abilities to impart well-defined folds. In the last decade, chemists have discovered foldamers: non-natural oligomers and polymers also prone to adopt folded structures. The emergence of foldamers has far reaching implications. A new major long term prospect is open to chemistry: the de novo synthesis of artificial objects resembling biopolymers in terms of their size, complexity, and efficiency at achieving defined functions, yet having chemical structures beyond the reach of biopolymers amenable to new properties and functions. The PI of this project has shown internationally recognized leadership in the development of a class of foldamers, aromatic oligoamides, whose features arguably make them the most suitable candidates to systematically explore what folded structures beyond biopolymers give access to. This project aims at developing methods to allow the routine fabrication of 20-40 units long aromatic oligoamide foldamers (6-15 kDa) designed to fold into artificial molecular containers having engineerable cavities and surfaces for molecular recognition of organic substrates, in particular large peptides and saccharides, polymers, and proteins. The methodology rests on modelling based design, multistep organic synthesis of heterocyclic monomers and their assembly into long sequences, structural elucidation using, among other techniques, x-ray crystallography, and the physico-chemical characterization of molecular recognition events.
Nature has evolved ultimate chemical functions based on controlling and altering conformation of its molecular machinery. Prominent examples include enzyme catalysis and information storage/duplication in nucleic acids. These achievements are based on large and complex yet remarkably defined structures obtained through folding of polymeric chains and a subtle interplay of non-covalent forces. Nature uses a limited set of building blocks – e.g. twenty amino-acids and four nucleobases – with specific abilities to impart well-defined folds. In the last decade, chemists have discovered foldamers: non-natural oligomers and polymers also prone to adopt folded structures. The emergence of foldamers has far reaching implications. A new major long term prospect is open to chemistry: the de novo synthesis of artificial objects resembling biopolymers in terms of their size, complexity, and efficiency at achieving defined functions, yet having chemical structures beyond the reach of biopolymers amenable to new properties and functions. The PI of this project has shown internationally recognized leadership in the development of a class of foldamers, aromatic oligoamides, whose features arguably make them the most suitable candidates to systematically explore what folded structures beyond biopolymers give access to. This project aims at developing methods to allow the routine fabrication of 20-40 units long aromatic oligoamide foldamers (6-15 kDa) designed to fold into artificial molecular containers having engineerable cavities and surfaces for molecular recognition of organic substrates, in particular large peptides and saccharides, polymers, and proteins. The methodology rests on modelling based design, multistep organic synthesis of heterocyclic monomers and their assembly into long sequences, structural elucidation using, among other techniques, x-ray crystallography, and the physico-chemical characterization of molecular recognition events.
Project acronym ADJUV-ANT VACCINES
Project Elucidating the Molecular Mechanisms of Synthetic Saponin Adjuvants and Development of Novel Self-Adjuvanting Vaccines
Researcher (PI) Alberto FERNANDEZ TEJADA
Host Institution (HI) ASOCIACION CENTRO DE INVESTIGACION COOPERATIVA EN BIOCIENCIAS
Summary The clinical success of anticancer and antiviral vaccines often requires the use of an adjuvant, a substance that helps stimulate the body's immune response to the vaccine, making it work better. However, few adjuvants are sufficiently potent and non-toxic for clinical use; moreover, it is not really known how they work. Current vaccine approaches based on weak carbohydrate and glycopeptide antigens are not being particularly effective to induce the human immune system to mount an effective fight against cancer. Despite intensive research and several clinical trials, no such carbohydrate-based antitumor vaccine has yet been approved for public use. In this context, the proposed project has a double, ultimate goal based on applying chemistry to address the above clear gaps in the adjuvant-vaccine field. First, I will develop new improved adjuvants and novel chemical strategies towards more effective, self-adjuvanting synthetic vaccines. Second, I will probe deeply into the molecular mechanisms of the synthetic constructs by combining extensive immunological evaluations with molecular target identification and detailed conformational studies. Thus, the singularity of this multidisciplinary proposal stems from the integration of its main objectives and approaches connecting chemical synthesis and chemical/structural biology with cellular and molecular immunology. This ground-breaking project at the chemistry-biology frontier will allow me to establish my own independent research group and explore key unresolved mechanistic questions in the adjuvant/vaccine arena with extraordinary chemical precision. Therefore, with this transformative and timely research program I aim to (a) develop novel synthetic antitumor and antiviral vaccines with improved properties and efficacy for their prospective translation into the clinic and (b) gain new critical insights into the molecular basis and three-dimensional structure underlying the biological activity of these constructs.
The clinical success of anticancer and antiviral vaccines often requires the use of an adjuvant, a substance that helps stimulate the body's immune response to the vaccine, making it work better. However, few adjuvants are sufficiently potent and non-toxic for clinical use; moreover, it is not really known how they work. Current vaccine approaches based on weak carbohydrate and glycopeptide antigens are not being particularly effective to induce the human immune system to mount an effective fight against cancer. Despite intensive research and several clinical trials, no such carbohydrate-based antitumor vaccine has yet been approved for public use. In this context, the proposed project has a double, ultimate goal based on applying chemistry to address the above clear gaps in the adjuvant-vaccine field. First, I will develop new improved adjuvants and novel chemical strategies towards more effective, self-adjuvanting synthetic vaccines. Second, I will probe deeply into the molecular mechanisms of the synthetic constructs by combining extensive immunological evaluations with molecular target identification and detailed conformational studies. Thus, the singularity of this multidisciplinary proposal stems from the integration of its main objectives and approaches connecting chemical synthesis and chemical/structural biology with cellular and molecular immunology. This ground-breaking project at the chemistry-biology frontier will allow me to establish my own independent research group and explore key unresolved mechanistic questions in the adjuvant/vaccine arena with extraordinary chemical precision. Therefore, with this transformative and timely research program I aim to (a) develop novel synthetic antitumor and antiviral vaccines with improved properties and efficacy for their prospective translation into the clinic and (b) gain new critical insights into the molecular basis and three-dimensional structure underlying the biological activity of these constructs.
Project acronym AEDNA
Project Amorphous and Evolutionary DNA Nanotechnology
Researcher (PI) Friedrich SIMMEL
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Summary Amorphous and evolutionary DNA nanotechnology (AEDNA) explores novel conceptual directions and applications for DNA nanotechnology, which are based on intelligent, DNA-programmed soft hybrid materials, and the utilization of evolutionary principles for the optimization of nucleic acid nanocomponents. Amorphous DNA nanotechnology first aims at the creation of cell-sized, DNA-programmed microgels – DNA cells – with sensor, computation, communication, and actuator functions. Interacting DNA cells will be arranged into chemical cell consortia and artificial tissues using microfluidics, micromanipulation and 3D bioprinting techniques. Spatially distributed chemical circuits will then be utilized to establish collective behaviors such as quorum sensing, pattern formation, and self-differentiation within these consortia and tissues. The approach will be further scaled up to produce multicomponent DNA gel compositions that become active and differentiate upon mixing. In evolutionary nanotechnology, techniques derived from directed molecular evolution experiments will be applied to optimize the arrangement of functional nucleic acids on DNA and RNA nanoscaffolds. Compartmentalization and microfluidics will be utilized to screen for nucleic acid nanostructures capable of superstructure formation, and also for the development of ligand-sensitive components for molecular programming. An evolutionary approach will then be applied to amorphous DNA cells, resulting in DNA cell populations which contain individuals with different molecular identities. The proposal will pave the way for the creation of macroscopic materials with DNA-programmed intelligence, resulting in novel applications for DNA nanotechnology and molecular programming in diverse fields such as environmental and biological sensing, biocatalysis, smart adaptive materials, and soft robotics.
Amorphous and evolutionary DNA nanotechnology (AEDNA) explores novel conceptual directions and applications for DNA nanotechnology, which are based on intelligent, DNA-programmed soft hybrid materials, and the utilization of evolutionary principles for the optimization of nucleic acid nanocomponents. Amorphous DNA nanotechnology first aims at the creation of cell-sized, DNA-programmed microgels – DNA cells – with sensor, computation, communication, and actuator functions. Interacting DNA cells will be arranged into chemical cell consortia and artificial tissues using microfluidics, micromanipulation and 3D bioprinting techniques. Spatially distributed chemical circuits will then be utilized to establish collective behaviors such as quorum sensing, pattern formation, and self-differentiation within these consortia and tissues. The approach will be further scaled up to produce multicomponent DNA gel compositions that become active and differentiate upon mixing. In evolutionary nanotechnology, techniques derived from directed molecular evolution experiments will be applied to optimize the arrangement of functional nucleic acids on DNA and RNA nanoscaffolds. Compartmentalization and microfluidics will be utilized to screen for nucleic acid nanostructures capable of superstructure formation, and also for the development of ligand-sensitive components for molecular programming. An evolutionary approach will then be applied to amorphous DNA cells, resulting in DNA cell populations which contain individuals with different molecular identities. The proposal will pave the way for the creation of macroscopic materials with DNA-programmed intelligence, resulting in novel applications for DNA nanotechnology and molecular programming in diverse fields such as environmental and biological sensing, biocatalysis, smart adaptive materials, and soft robotics.
Project acronym AEROCAT
Project Non-ordered nanoparticle superstructures – aerogels as efficient (electro-)catalysts
Researcher (PI) Alexander Eychmüller
Summary "AEROCAT aims at the elucidation of the potential of nanoparticle derived aerogels in catalytic applications. The materials will be produced from a variety of nanoparticles available in colloidal solutions, amongst which are metals and metal oxides. The evolving aerogels are extremely light, highly porous solids and have been demonstrated to exhibit in many cases the important properties of the nanosized objects they consist of instead of simply those of the respective bulk solids. The resulting aerogel materials will be characterized with respect to their morphology and composition and their resulting (electro-)catalytic properties examined in the light of the inherent electronic nature of the nanosized constituents. Using the knowledge gained within the project the aerogel materials will be further re-processed in order to exploit their full potential relevant to catalysis and electrocatalysis. From the vast variety of possible applications of nanoparticle-based hydro- and aerogels like thermoelectrics, LEDs, pollutant clearance, sensorics and others we choose our strictly focused approach (i) due to the paramount importance of catalysis for the Chemical Industry, (ii) because we have successfully studied the Ethanol electrooxidation on a Pd-nanoparticle aerogel, (iii) we have patented on the oxygen reduction reaction in fuel cells with bimetallic aerogels, (iv) and we gained first and extremely promising results on the semi-hydrogenation of Acetylene on a mixed Pd/ZnO-nanoparticle aerogel. With this we are on the forefront of a research field which impact might not be overestimated. We should quickly explore its potentials and transfer on a short track the knowledge gained into pre-industrial testing."
"AEROCAT aims at the elucidation of the potential of nanoparticle derived aerogels in catalytic applications. The materials will be produced from a variety of nanoparticles available in colloidal solutions, amongst which are metals and metal oxides. The evolving aerogels are extremely light, highly porous solids and have been demonstrated to exhibit in many cases the important properties of the nanosized objects they consist of instead of simply those of the respective bulk solids. The resulting aerogel materials will be characterized with respect to their morphology and composition and their resulting (electro-)catalytic properties examined in the light of the inherent electronic nature of the nanosized constituents. Using the knowledge gained within the project the aerogel materials will be further re-processed in order to exploit their full potential relevant to catalysis and electrocatalysis. From the vast variety of possible applications of nanoparticle-based hydro- and aerogels like thermoelectrics, LEDs, pollutant clearance, sensorics and others we choose our strictly focused approach (i) due to the paramount importance of catalysis for the Chemical Industry, (ii) because we have successfully studied the Ethanol electrooxidation on a Pd-nanoparticle aerogel, (iii) we have patented on the oxygen reduction reaction in fuel cells with bimetallic aerogels, (iv) and we gained first and extremely promising results on the semi-hydrogenation of Acetylene on a mixed Pd/ZnO-nanoparticle aerogel. With this we are on the forefront of a research field which impact might not be overestimated. We should quickly explore its potentials and transfer on a short track the knowledge gained into pre-industrial testing."
Project acronym AMPCAT
Project Self-Amplifying Stereodynamic Catalysts in Enantioselective Catalysis
Researcher (PI) Oliver Trapp
Host Institution (HI) RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Summary Think about an enantioselective catalyst, which can switch its enantioselectivity and which can be imprinted and provides self-amplification by its own chiral reaction product. Think about a catalyst, which can be fine-tuned for efficient stereoselective synthesis of drugs and other materials, e.g. polymers. Highly promising reactions such as enantioselective autocatalysis (Soai reaction) and chiral catalysts undergoing dynamic interconversions, e.g. BIPHEP ligands, are still not understood. Their application is very limited to a few compounds, which opens the field for novel investigations. I propose the development of a smart or switchable chiral ligand undergoing dynamic interconversions. These catalysts will be tuned by their reaction product, and this leads to self-amplification of one of the stereoisomers. I propose a novel fundamental mechanism which has the potential to overcome the limitations of the Soai reaction, exploiting the full potential of enantioselective catalysis. As representatives of enantioselective self-amplifying stereodynamic catalysts a novel class of diazirine based ligands will be developed, their interconversion barrier is tuneable between 80 and 130 kJ/mol. Specifically, following areas will be explored: 1. Investigation of the kinetics and thermodynamics of the Soai reaction as a model reaction by analysis of large sets of kinetic data. 2. Ligands with diaziridine moieties with flexible structure will be designed and investigated, to control the enantioselectivity. 3. Design of a ligand receptor group for product interaction to switch the chirality. Study of self-amplification in enantioselective processes. 4. Enantioselective hydrogenations, Diels-Alder reactions, epoxidations and reactions generating multiple stereocenters will be targeted.
Think about an enantioselective catalyst, which can switch its enantioselectivity and which can be imprinted and provides self-amplification by its own chiral reaction product. Think about a catalyst, which can be fine-tuned for efficient stereoselective synthesis of drugs and other materials, e.g. polymers. Highly promising reactions such as enantioselective autocatalysis (Soai reaction) and chiral catalysts undergoing dynamic interconversions, e.g. BIPHEP ligands, are still not understood. Their application is very limited to a few compounds, which opens the field for novel investigations. I propose the development of a smart or switchable chiral ligand undergoing dynamic interconversions. These catalysts will be tuned by their reaction product, and this leads to self-amplification of one of the stereoisomers. I propose a novel fundamental mechanism which has the potential to overcome the limitations of the Soai reaction, exploiting the full potential of enantioselective catalysis. As representatives of enantioselective self-amplifying stereodynamic catalysts a novel class of diazirine based ligands will be developed, their interconversion barrier is tuneable between 80 and 130 kJ/mol. Specifically, following areas will be explored: 1. Investigation of the kinetics and thermodynamics of the Soai reaction as a model reaction by analysis of large sets of kinetic data. 2. Ligands with diaziridine moieties with flexible structure will be designed and investigated, to control the enantioselectivity. 3. Design of a ligand receptor group for product interaction to switch the chirality. Study of self-amplification in enantioselective processes. 4. Enantioselective hydrogenations, Diels-Alder reactions, epoxidations and reactions generating multiple stereocenters will be targeted.
Project acronym AMPLIPORE
Project Understanding negative gas adsorption in highly porous networks for the design of pressure amplifying materials
Researcher (PI) Stefan Kaskel
Summary Negative gas adsorption (NGA) is a new, counterintuitive and paradoxical phenomenon, for the first time reported by my group in 2016: Normal solid materials with significant outer or inner surface area always take up gas when the pressure in the surrounding reservoir is increased (adsorption). NGA networks instead react at a certain point in the opposite direction: They release gas upon external pressure increase, leading to an overall pressure amplification in a closed system. Comparable phenomena have never been reported before. What is so exciting about NGA? We have a unique material in hand, that counteracts to an external force by force amplification. So far NGA has solely been observed in one of our new coordination polymers, featuring a colossal selfcompression associated with a mesopore-to-micropore transformation. Gas pressure amplifying materials could lead to important innovations in gas releasing rescue systems, pneumatic control systems (production, transportation), micropumps, microfluidic devices, pneumatic actuators, and artificial lungs. A fundamental understanding of the physical mechanisms, structures, and thermodynamic boundary conditions is an essential prerequisite for any industrial application of this counterintuitive phenomenon. Combining strong synthetic methodologies with advanced analytical techniques, AMPLIPORE will elucidate the characteristic molecular and mesoscopic materials signatures as well as thermodynamic boundary conditions of NGA phenomena. We will elaborate a generic NGA-materials concept to tailor the pressure amplification and explore temperature and pressure ranges at which NGA can be applied. Developing tailormade instrumentation for kinetic investigations of NGA will give fundamental insights into the intrinsic and macroscopic dynamics of crystal-to-crystal transformations for applications in micropneumatic systems.
Negative gas adsorption (NGA) is a new, counterintuitive and paradoxical phenomenon, for the first time reported by my group in 2016: Normal solid materials with significant outer or inner surface area always take up gas when the pressure in the surrounding reservoir is increased (adsorption). NGA networks instead react at a certain point in the opposite direction: They release gas upon external pressure increase, leading to an overall pressure amplification in a closed system. Comparable phenomena have never been reported before. What is so exciting about NGA? We have a unique material in hand, that counteracts to an external force by force amplification. So far NGA has solely been observed in one of our new coordination polymers, featuring a colossal selfcompression associated with a mesopore-to-micropore transformation. Gas pressure amplifying materials could lead to important innovations in gas releasing rescue systems, pneumatic control systems (production, transportation), micropumps, microfluidic devices, pneumatic actuators, and artificial lungs. A fundamental understanding of the physical mechanisms, structures, and thermodynamic boundary conditions is an essential prerequisite for any industrial application of this counterintuitive phenomenon. Combining strong synthetic methodologies with advanced analytical techniques, AMPLIPORE will elucidate the characteristic molecular and mesoscopic materials signatures as well as thermodynamic boundary conditions of NGA phenomena. We will elaborate a generic NGA-materials concept to tailor the pressure amplification and explore temperature and pressure ranges at which NGA can be applied. Developing tailormade instrumentation for kinetic investigations of NGA will give fundamental insights into the intrinsic and macroscopic dynamics of crystal-to-crystal transformations for applications in micropneumatic systems.
Project acronym ANaPSyS
Project Artificial Natural Products System Synthesis
Researcher (PI) Tanja Gaich
Host Institution (HI) UNIVERSITAT KONSTANZ
Summary "Traditionally, natural products are classified into ""natural product families"". Within a family all congeners display specific structure elements, owing to their common biosynthetic pathway. This suggests a bio-inspired or ""collective synthesis"", as has been devised by D: W. MacMillan. However, a biosynthetic pathway is confined to these structure elements, thus limiting synthesis with regard to structure diversification. In this research proposal the applicant exemplarily devises a strategic concept to overcome these limitations, by replacing the dogma of ""retrosynthetic analysis"" with ""structure pattern recognition"". This concept is termed ""Artificial Natural Product Systems Synthesis — ANaPSyS"", and aims to supersede the current ""logic of chemical synthesis"" as a standard practice in this field. ANaPSyS exclusively categorizes natural products based on structural relationships — regardless of biogenetic origin. The structure pattern analysis groups natural products according to their shared core structure, and thereof creates a common precursor called ""privileged intermediate (PI)"". This intermediate is resembled in each of these natural products and is architecturally less complex. As a result every member of this natural product group can originate from a different natural product family and is obtained via this ""privileged intermediate"", which serves as basis for the artificial synthetic network. With ANaPSyS a synthetic route is not restricted to a single target structure anymore (as in conventional synthesis). In comparison with bio-inspired synthesis, which is limited to a single natural product family, ANaPSyS enables the synthesis of a whole set of natural product families. With every synthesis accomplished, the network is upgraded — hence diversification leads to a rise in revenue. As a consequence, synthetic efficiency is drastically enhanced, therefore profoundly boosting and facilitating lead structure development. "
"Traditionally, natural products are classified into ""natural product families"". Within a family all congeners display specific structure elements, owing to their common biosynthetic pathway. This suggests a bio-inspired or ""collective synthesis"", as has been devised by D: W. MacMillan. However, a biosynthetic pathway is confined to these structure elements, thus limiting synthesis with regard to structure diversification. In this research proposal the applicant exemplarily devises a strategic concept to overcome these limitations, by replacing the dogma of ""retrosynthetic analysis"" with ""structure pattern recognition"". This concept is termed ""Artificial Natural Product Systems Synthesis — ANaPSyS"", and aims to supersede the current ""logic of chemical synthesis"" as a standard practice in this field. ANaPSyS exclusively categorizes natural products based on structural relationships — regardless of biogenetic origin. The structure pattern analysis groups natural products according to their shared core structure, and thereof creates a common precursor called ""privileged intermediate (PI)"". This intermediate is resembled in each of these natural products and is architecturally less complex. As a result every member of this natural product group can originate from a different natural product family and is obtained via this ""privileged intermediate"", which serves as basis for the artificial synthetic network. With ANaPSyS a synthetic route is not restricted to a single target structure anymore (as in conventional synthesis). In comparison with bio-inspired synthesis, which is limited to a single natural product family, ANaPSyS enables the synthesis of a whole set of natural product families. With every synthesis accomplished, the network is upgraded — hence diversification leads to a rise in revenue. As a consequence, synthetic efficiency is drastically enhanced, therefore profoundly boosting and facilitating lead structure development. "
Project acronym ANISOGEL
Project Injectable anisotropic microgel-in-hydrogel matrices for spinal cord repair
Researcher (PI) Laura De Laporte
Host Institution (HI) DWI LEIBNIZ-INSTITUT FUR INTERAKTIVE MATERIALIEN EV
Summary This project will engineer an injectable biomaterial that forms an anisotropic microheterogeneous structure in vivo. Injectable hydrogels enable a minimal invasive in situ generation of matrices for the regeneration of tissues and organs, but currently lack structural organization and unidirectional orientation. The anisotropic, injectable hydrogels to be developed will mimic local extracellular matrix architectures that cells encounter in complex tissues (e.g. nerves, muscles). This project aims for the development of a biomimetic scaffold for spinal cord regeneration. To realize such a major breakthrough, my group will focus on three research objectives. i) Poly(ethylene glycol) microgel-in-hydrogel matrices will be fabricated with the ability to create macroscopic order due to microgel shape anisotropy and magnetic alignment. Barrel-like microgels will be prepared using an in-mold polymerization technique. Their ability to self-assemble will be investigated in function of their dimensions, aspect ratio, crosslinking density, and volume fraction. Superparamagnetic nanoparticles will be included into the microgels to enable unidirectional orientation by means of a magnetic field. Subsequently, the oriented microgels will be interlocked within a master hydrogel. ii) The microgel-in-hydrogel matrices will be equipped with (bio)functional properties for spinal cord regeneration, i.e., to control and optimize mechanical anisotropy and biological signaling by in vitro cell growth experiments. iii) Selected hydrogel composites will be injected after rat spinal cord injury and directional tissue growth and animal functional behavior will be analyzed. Succesful fabrication of the proposed microgel-in-hydrogel matrix will provide a new type of biomaterial, which enables investigating the effect of an anisotropic structure on physiological and pathological processes in vivo. This is a decisive step towards creating a clinical healing matrix for anisotropic tissue repair.
This project will engineer an injectable biomaterial that forms an anisotropic microheterogeneous structure in vivo. Injectable hydrogels enable a minimal invasive in situ generation of matrices for the regeneration of tissues and organs, but currently lack structural organization and unidirectional orientation. The anisotropic, injectable hydrogels to be developed will mimic local extracellular matrix architectures that cells encounter in complex tissues (e.g. nerves, muscles). This project aims for the development of a biomimetic scaffold for spinal cord regeneration. To realize such a major breakthrough, my group will focus on three research objectives. i) Poly(ethylene glycol) microgel-in-hydrogel matrices will be fabricated with the ability to create macroscopic order due to microgel shape anisotropy and magnetic alignment. Barrel-like microgels will be prepared using an in-mold polymerization technique. Their ability to self-assemble will be investigated in function of their dimensions, aspect ratio, crosslinking density, and volume fraction. Superparamagnetic nanoparticles will be included into the microgels to enable unidirectional orientation by means of a magnetic field. Subsequently, the oriented microgels will be interlocked within a master hydrogel. ii) The microgel-in-hydrogel matrices will be equipped with (bio)functional properties for spinal cord regeneration, i.e., to control and optimize mechanical anisotropy and biological signaling by in vitro cell growth experiments. iii) Selected hydrogel composites will be injected after rat spinal cord injury and directional tissue growth and animal functional behavior will be analyzed. Succesful fabrication of the proposed microgel-in-hydrogel matrix will provide a new type of biomaterial, which enables investigating the effect of an anisotropic structure on physiological and pathological processes in vivo. This is a decisive step towards creating a clinical healing matrix for anisotropic tissue repair.
Project acronym ANTIBACTERIALS
Project Natural products and their cellular targets: A multidisciplinary strategy for antibacterial drug discovery
Researcher (PI) Stephan Axel Sieber
Summary After decades of successful treatment of bacterial infections with antibiotics, formerly treatable bacteria have developed drug resistance and consequently pose a major threat to public health. To address the urgent need for effective antibacterial drugs we will develop a streamlined chemical-biology platform that facilitates the consolidated identification and structural elucidation of natural products together with their dedicated cellular targets. This innovative concept overcomes several limitations of classical drug discovery processes by a chemical strategy that focuses on a directed isolation, enrichment and identification procedure for certain privileged natural product subclasses. This proposal consists of four specific aims: 1) synthesizing enzyme active site mimetics that capture protein reactive natural products out of complex natural sources, 2) designing natural product based probes to identify their cellular targets by a method called activity based protein profiling , 3) developing a traceless photocrosslinking strategy for the target identification of selected non-reactive natural products, and 4) application of all probes to identify novel enzyme activities linked to viability, resistance and pathogenesis. Moreover, the compounds will be used to monitor the infection process during invasion into eukaryotic cells and will reveal host specific targets that promote and support bacterial pathogenesis. Inhibition of these targets is a novel and so far neglected approach in the treatment of infectious diseases. We anticipate that these studies will provide a powerful pharmacological platform for the development of potent natural product derived antibacterial agents directed toward novel therapeutic targets.
After decades of successful treatment of bacterial infections with antibiotics, formerly treatable bacteria have developed drug resistance and consequently pose a major threat to public health. To address the urgent need for effective antibacterial drugs we will develop a streamlined chemical-biology platform that facilitates the consolidated identification and structural elucidation of natural products together with their dedicated cellular targets. This innovative concept overcomes several limitations of classical drug discovery processes by a chemical strategy that focuses on a directed isolation, enrichment and identification procedure for certain privileged natural product subclasses. This proposal consists of four specific aims: 1) synthesizing enzyme active site mimetics that capture protein reactive natural products out of complex natural sources, 2) designing natural product based probes to identify their cellular targets by a method called activity based protein profiling , 3) developing a traceless photocrosslinking strategy for the target identification of selected non-reactive natural products, and 4) application of all probes to identify novel enzyme activities linked to viability, resistance and pathogenesis. Moreover, the compounds will be used to monitor the infection process during invasion into eukaryotic cells and will reveal host specific targets that promote and support bacterial pathogenesis. Inhibition of these targets is a novel and so far neglected approach in the treatment of infectious diseases. We anticipate that these studies will provide a powerful pharmacological platform for the development of potent natural product derived antibacterial agents directed toward novel therapeutic targets.
Project acronym APACHE
Project Atmospheric Pressure plAsma meets biomaterials for bone Cancer HEaling
Researcher (PI) Cristina CANAL BARNILS
Host Institution (HI) UNIVERSITAT POLITECNICA DE CATALUNYA
Summary Cold atmospheric pressure plasmas (APP) have been reported to selectively kill cancer cells without damaging the surrounding tissues. Studies have been conducted on a variety of cancer types but to the best of our knowledge not on any kind of bone cancer. Treatment options for bone cancer include surgery, chemotherapy, etc. and may involve the use of bone grafting biomaterials to replace the surgically removed bone. APACHE brings a totally different and ground-breaking approach in the design of a novel therapy for bone cancer by taking advantage of the active species generated by APP in combination with biomaterials to deliver the active species locally in the diseased site. The feasibility of this approach is rooted in the evidence that the cellular effects of APP appear to strongly involve the suite of reactive species created by plasmas, which can be derived from a) direct treatment of the malignant cells by APP or b) indirect treatment of the liquid media by APP which is then put in contact with the cancer cells. In APACHE we aim to investigate the fundamentals involved in the lethal effects of cold plasmas on bone cancer cells, and to develop improved bone cancer therapies. To achieve this we will take advantage of the highly reactive species generated by APP in the liquid media, which we will use in an incremental strategy: i) to investigate the effects of APP treated liquid on bone cancer cells, ii) to evaluate the potential of combining APP treated liquid in a hydrogel vehicle with/wo CaP biomaterials and iii) to ascertain the potential three directional interactions between APP reactive species in liquid medium with biomaterials and with chemotherapeutic drugs. The methodological approach will involve an interdisciplinary team, dealing with plasma diagnostics in gas and liquid media; with cell biology and the effects of APP treated with bone tumor cells and its combination with biomaterials and/or with anticancer drugs.
Cold atmospheric pressure plasmas (APP) have been reported to selectively kill cancer cells without damaging the surrounding tissues. Studies have been conducted on a variety of cancer types but to the best of our knowledge not on any kind of bone cancer. Treatment options for bone cancer include surgery, chemotherapy, etc. and may involve the use of bone grafting biomaterials to replace the surgically removed bone. APACHE brings a totally different and ground-breaking approach in the design of a novel therapy for bone cancer by taking advantage of the active species generated by APP in combination with biomaterials to deliver the active species locally in the diseased site. The feasibility of this approach is rooted in the evidence that the cellular effects of APP appear to strongly involve the suite of reactive species created by plasmas, which can be derived from a) direct treatment of the malignant cells by APP or b) indirect treatment of the liquid media by APP which is then put in contact with the cancer cells. In APACHE we aim to investigate the fundamentals involved in the lethal effects of cold plasmas on bone cancer cells, and to develop improved bone cancer therapies. To achieve this we will take advantage of the highly reactive species generated by APP in the liquid media, which we will use in an incremental strategy: i) to investigate the effects of APP treated liquid on bone cancer cells, ii) to evaluate the potential of combining APP treated liquid in a hydrogel vehicle with/wo CaP biomaterials and iii) to ascertain the potential three directional interactions between APP reactive species in liquid medium with biomaterials and with chemotherapeutic drugs. The methodological approach will involve an interdisciplinary team, dealing with plasma diagnostics in gas and liquid media; with cell biology and the effects of APP treated with bone tumor cells and its combination with biomaterials and/or with anticancer drugs.
Project acronym APHOTOREACTOR
Project Entirely Self-organized: Arrayed Single-Particle-in-a-Cavity Reactors for Highly Efficient and Selective Catalytic/Photocatalytic Energy Conversion and Solar Light Reaction Engineering
Researcher (PI) Patrik Schmuki
Host Institution (HI) FRIEDRICH-ALEXANDER-UNIVERSITAET ERLANGEN NUERNBERG
Summary The proposal is built on the core idea to use an ensemble of multiple level self-organization processes to create a next generation photocatalytic platform that provides unprecedented property and reactivity control. As a main output, the project will yield a novel highly precise combined catalyst/photocatalyst assembly to: 1) provide a massive step ahead in photocatalytic applications such as direct solar hydrogen generation, pollution degradation (incl. CO2 decomposition), N2 fixation, or photocatalytic organic synthesis. It will drastically enhance efficiency and selectivity of photocatalytic reactions, and enable a high number of organic synthetic reactions to be carried out economically (and ecologically) via combined catalytic/photocatalytic pathways. Even more, it will establish an entirely new generation of "100% depoisoning", anti-aggregation catalysts with substantially enhanced catalyst life-time. For this, a series of self-assembly processes on the mesoscale will be used to create highly uniform arrays of single-catalyst-particle-in-a-single-TiO2-cavity; target is a 100% reliable placement of a single <10 nm particle in a 10 nm cavity. Thus catalytic features of, for example Pt nanoparticles, can ideally interact with the photocatalytic properties of a TiO2 cavity. The cavity will be optimized for optical and electronic properties by doping and band-gap engineering; the geometry will be tuned to the range of a few nm.. This nanoscopic design yields to a radical change in the controllability of length and time-scales (reactant, charge carrier and ionic transport in the substrate) in combined photocatalytic/catalytic reactions. It is of key importance that all nanoscale assembly principles used in this work are scalable and allow to create square meters of nanoscopically ordered catalyst surfaces. We target to demonstrate the feasibility of the implementation of the nanoscale principles in a prototype macroscopic reactor.
The proposal is built on the core idea to use an ensemble of multiple level self-organization processes to create a next generation photocatalytic platform that provides unprecedented property and reactivity control. As a main output, the project will yield a novel highly precise combined catalyst/photocatalyst assembly to: 1) provide a massive step ahead in photocatalytic applications such as direct solar hydrogen generation, pollution degradation (incl. CO2 decomposition), N2 fixation, or photocatalytic organic synthesis. It will drastically enhance efficiency and selectivity of photocatalytic reactions, and enable a high number of organic synthetic reactions to be carried out economically (and ecologically) via combined catalytic/photocatalytic pathways. Even more, it will establish an entirely new generation of "100% depoisoning", anti-aggregation catalysts with substantially enhanced catalyst life-time. For this, a series of self-assembly processes on the mesoscale will be used to create highly uniform arrays of single-catalyst-particle-in-a-single-TiO2-cavity; target is a 100% reliable placement of a single <10 nm particle in a 10 nm cavity. Thus catalytic features of, for example Pt nanoparticles, can ideally interact with the photocatalytic properties of a TiO2 cavity. The cavity will be optimized for optical and electronic properties by doping and band-gap engineering; the geometry will be tuned to the range of a few nm.. This nanoscopic design yields to a radical change in the controllability of length and time-scales (reactant, charge carrier and ionic transport in the substrate) in combined photocatalytic/catalytic reactions. It is of key importance that all nanoscale assembly principles used in this work are scalable and allow to create square meters of nanoscopically ordered catalyst surfaces. We target to demonstrate the feasibility of the implementation of the nanoscale principles in a prototype macroscopic reactor.
Project acronym ARTIST
Project Artificial cell-cell interactions for light switchable cell organization and signaling
Researcher (PI) Seraphine Valeska Wegner
Summary The bottom-up assembly of tissue from cellular building blocks constitutes a promising, yet highly challenging approach to engineer complex tissues. The challenge lies in controlling cell-cell interactions, which determine how cells organize with respect to each other, how they work together and consequently whether such a multicellular architecture will be functional. The limited spatial and temporal control over cell-cell interactions current biological and chemical approaches provide severely restricts bottom-up tissue engineering. Here, I propose a new way to control cell-cell interactions. I aim to regulate cell-cell interactions with visible light using proteins that reversibly homo- or heterodimerize under blue or red light. These photoswitchable cell-cell interactions provide sustainable, non-invasive, dynamic and reversible control over cell-cell interactions with unprecedented spatial and temporal resolution. First of all, we will focus on various light dependent protein interactions to mediate cell-cell contacts. The detailed characterization (strength, dynamics, interaction modes and orthogonality) of these new photoswitchable cell-cell interactions will provide the framework for the bottom-up construction of tissue-like structures. Secondly, we will use these photoswitchable cell-cell interactions to assemble cells into multicellular architectures with predictable and programmable organization. The dynamic and reversible nature of the photoswitchable contacts will allow us to locally alter interactions at any point in time, to rearrange and obtain asymmetric multicellular structures, which are typical of tissues. Finally, we will also explore how the photoswitchable cell-cell interactions alter cell behavior and signaling. Ultimately, this will pave the way for the bottom-up assembly of multicellular architectures, enabling us to control precisely and dynamically their organization in space and time as well as regulate how cells work together.
The bottom-up assembly of tissue from cellular building blocks constitutes a promising, yet highly challenging approach to engineer complex tissues. The challenge lies in controlling cell-cell interactions, which determine how cells organize with respect to each other, how they work together and consequently whether such a multicellular architecture will be functional. The limited spatial and temporal control over cell-cell interactions current biological and chemical approaches provide severely restricts bottom-up tissue engineering. Here, I propose a new way to control cell-cell interactions. I aim to regulate cell-cell interactions with visible light using proteins that reversibly homo- or heterodimerize under blue or red light. These photoswitchable cell-cell interactions provide sustainable, non-invasive, dynamic and reversible control over cell-cell interactions with unprecedented spatial and temporal resolution. First of all, we will focus on various light dependent protein interactions to mediate cell-cell contacts. The detailed characterization (strength, dynamics, interaction modes and orthogonality) of these new photoswitchable cell-cell interactions will provide the framework for the bottom-up construction of tissue-like structures. Secondly, we will use these photoswitchable cell-cell interactions to assemble cells into multicellular architectures with predictable and programmable organization. The dynamic and reversible nature of the photoswitchable contacts will allow us to locally alter interactions at any point in time, to rearrange and obtain asymmetric multicellular structures, which are typical of tissues. Finally, we will also explore how the photoswitchable cell-cell interactions alter cell behavior and signaling. Ultimately, this will pave the way for the bottom-up assembly of multicellular architectures, enabling us to control precisely and dynamically their organization in space and time as well as regulate how cells work together.
Project acronym ASMIDIAS
Project Asymmetric microenvironments by directed assembly: Control of geometry, topography, surface biochemistry and mechanical properties via a microscale modular design principle
Researcher (PI) Holger Dr. Schönherr
Host Institution (HI) UNIVERSITAET SIEGEN
Summary The interaction of cells with the extracellular matrix or neighboring cells plays a crucial role in many cellular functions, such as motility, differentiation and controlled cell death. Expanding on pioneering studies on defined 2-D model systems, the role of the currently known determinants (geometry, topography, biochemical functionality and mechanical properties) is currently addressed in more relevant 3-D matrices. However, there is a clear lack in currently available approaches to fabricate well defined microenvironments, which are asymmetric or in which these factors can be varied independently. The central objective of ASMIDIAS is the development of a novel route to asymmetric microenvironments for cell-matrix interaction studies. Inspired by molecular self-assembly on the one hand and guided macroscale assembly on the other hand, directed assembly of highly defined microfabricated building blocks will be exploited to this end. In this modular design approach different building blocks position themselves during assembly on pre-structured surfaces to afford enclosed volumes that are restricted by the walls of the blocks. The project relies on two central elements. For the guided assembly, the balance of attractive and repulsive interactions between the building blocks (and its dependence on the object dimensions) and the structured surface shall be controlled by appropriate surface chemistry and suitable guiding structures. To afford the required functionality, new approaches to (i) topographically structure, (ii) biochemically functionalize and pattern selected sides of the microscale building blocks and (iii) to control their surface elastic properties via surface-attached polymers and hydrogels, will be developed.The resulting unique asymmetric environments will facilitate novel insight into cell-matrix interactions, which possess considerable relevance in the areas of tissue engineering, cell (de)differentiation, bacteria-surface interactions and beyond.
The interaction of cells with the extracellular matrix or neighboring cells plays a crucial role in many cellular functions, such as motility, differentiation and controlled cell death. Expanding on pioneering studies on defined 2-D model systems, the role of the currently known determinants (geometry, topography, biochemical functionality and mechanical properties) is currently addressed in more relevant 3-D matrices. However, there is a clear lack in currently available approaches to fabricate well defined microenvironments, which are asymmetric or in which these factors can be varied independently. The central objective of ASMIDIAS is the development of a novel route to asymmetric microenvironments for cell-matrix interaction studies. Inspired by molecular self-assembly on the one hand and guided macroscale assembly on the other hand, directed assembly of highly defined microfabricated building blocks will be exploited to this end. In this modular design approach different building blocks position themselves during assembly on pre-structured surfaces to afford enclosed volumes that are restricted by the walls of the blocks. The project relies on two central elements. For the guided assembly, the balance of attractive and repulsive interactions between the building blocks (and its dependence on the object dimensions) and the structured surface shall be controlled by appropriate surface chemistry and suitable guiding structures. To afford the required functionality, new approaches to (i) topographically structure, (ii) biochemically functionalize and pattern selected sides of the microscale building blocks and (iii) to control their surface elastic properties via surface-attached polymers and hydrogels, will be developed.The resulting unique asymmetric environments will facilitate novel insight into cell-matrix interactions, which possess considerable relevance in the areas of tissue engineering, cell (de)differentiation, bacteria-surface interactions and beyond.
Project acronym ATHENE
Project Designing new technical wastewater treatment solutions targeted for organic micropollutant biodegradation, by understanding enzymatic pathways and assessing detoxification
Researcher (PI) Thomas Ternes
Host Institution (HI) Bundesanstalt fuer Gewaesserkunde
Summary The identification of degradation pathways relevant for organic micropollutants in biological wastewater treatment processes is currently a major gap, preventing a profound evaluation of the capability of biological wastewater treatment. By elucidating the responsible enzymatic reactions of mixed microbial populations this project will cover this gap and thereby allow finding technical solutions that harness the true potential of biological processes for an enhanced biodegradation and detoxification. Due to the multi-disciplinary approach Athene will have impacts on the fields of biological wastewater treatment, analytical and environmental chemistry, environmental microbiology, water and (eco)toxicity. The multi-disciplinary approach of the project requires the involvement of a co-investigator experienced in process engineering and microbiology in wastewater treatment. Athene will go far beyond state-of-the-art in the following fields: a) efficiency in chemical analysis and structure identification of transformation products at environmental relevant concentrations; b) identification of enzymatic pathways relevant for micropollutant degradation in biological wastewater treatment; c) designing innovative technical solutions to maximize biodegradation; d) map and model relevant enzymatic pathways for environmental concentrations. Furthermore, designing biological wastewater treatment processes by understanding enzymatic pathways relevant for organic micropollutants removal represents a paradigm shift for municipal wastewater treatment. In the context of the actual scientific discussion about the relevance of trace organics in the aquatic environment and in drinking water, this topic is deemed as highly innovative: for its potential of proposing new technical options as well as for the gain in understanding compound persistency. Finally enzymatic reactions as well as the treatment schemes will be assessed for there capability to reduce toxiciological effects.
The identification of degradation pathways relevant for organic micropollutants in biological wastewater treatment processes is currently a major gap, preventing a profound evaluation of the capability of biological wastewater treatment. By elucidating the responsible enzymatic reactions of mixed microbial populations this project will cover this gap and thereby allow finding technical solutions that harness the true potential of biological processes for an enhanced biodegradation and detoxification. Due to the multi-disciplinary approach Athene will have impacts on the fields of biological wastewater treatment, analytical and environmental chemistry, environmental microbiology, water and (eco)toxicity. The multi-disciplinary approach of the project requires the involvement of a co-investigator experienced in process engineering and microbiology in wastewater treatment. Athene will go far beyond state-of-the-art in the following fields: a) efficiency in chemical analysis and structure identification of transformation products at environmental relevant concentrations; b) identification of enzymatic pathways relevant for micropollutant degradation in biological wastewater treatment; c) designing innovative technical solutions to maximize biodegradation; d) map and model relevant enzymatic pathways for environmental concentrations. Furthermore, designing biological wastewater treatment processes by understanding enzymatic pathways relevant for organic micropollutants removal represents a paradigm shift for municipal wastewater treatment. In the context of the actual scientific discussion about the relevance of trace organics in the aquatic environment and in drinking water, this topic is deemed as highly innovative: for its potential of proposing new technical options as well as for the gain in understanding compound persistency. Finally enzymatic reactions as well as the treatment schemes will be assessed for there capability to reduce toxiciological effects.
Project acronym AUTOHEPARIN
Project Automated Synthesis of Heparin and Chondroitin Libraries for the Preparation of Diverse Carbohydrate Arrays
Researcher (PI) Peter Seeberger
Summary While heparin, a glacosaminoglycan (GAG) has served as an anticoagulant for more than 60 years, the structure-activity relationship of heparin and chondroitin sulfate for specific interactions with proteins are still poorly understood. It has become evident that defined lengths and sequences or patterns are responsible for binding to a particular protein and modulating its biological activity. Determination of the structure-activity relationships of heparins and chondroitins creates an opportunity to modulate processes underlying viral entry, angiogenesis, kidney diseases and diseases of the central nervous system. The isolation of pure GAGs is extremely tedious and chemical synthesis is often the only means to access defined oligosaccharides. Currently available synthetic methods for the preparation of heparins and chondroitins are time consuming and lack generality. Therefore, it is still impossible to create large collections of GAG oligosaccharides for systematic studies of GAG-protein interactions. The overall goal of the project is the development of all aspects of automated GAG synthesis, the procurement of a large collection of heparin and chondroitin oligosaccharides of 2-10 sugars in length with a linker for ready attachment to microarray surfaces and other tools. These molecular tools will be employed to study the interaction of GAGs with growth factors, chemokines and other proteins. The specific aims include: 1) Synthesis of uronic acid and galactosamine building blocks; 2) Development of a new linker for automated GAG solid phase synthesis; 3) Construction of a new automated oligosaccharide synthesizer; 4) Development of methods for the automated assembly of heparin and chondroitin sulfate oligosaccharides; 5) Synthesis of a collection of defined heparin and chondroitin sulfate oligosaccharides; 6) Construction of synthetic GAG microarrays and SPR; 7) Preparation of GAG dendrimers and quantum dots.
While heparin, a glacosaminoglycan (GAG) has served as an anticoagulant for more than 60 years, the structure-activity relationship of heparin and chondroitin sulfate for specific interactions with proteins are still poorly understood. It has become evident that defined lengths and sequences or patterns are responsible for binding to a particular protein and modulating its biological activity. Determination of the structure-activity relationships of heparins and chondroitins creates an opportunity to modulate processes underlying viral entry, angiogenesis, kidney diseases and diseases of the central nervous system. The isolation of pure GAGs is extremely tedious and chemical synthesis is often the only means to access defined oligosaccharides. Currently available synthetic methods for the preparation of heparins and chondroitins are time consuming and lack generality. Therefore, it is still impossible to create large collections of GAG oligosaccharides for systematic studies of GAG-protein interactions. The overall goal of the project is the development of all aspects of automated GAG synthesis, the procurement of a large collection of heparin and chondroitin oligosaccharides of 2-10 sugars in length with a linker for ready attachment to microarray surfaces and other tools. These molecular tools will be employed to study the interaction of GAGs with growth factors, chemokines and other proteins. The specific aims include: 1) Synthesis of uronic acid and galactosamine building blocks; 2) Development of a new linker for automated GAG solid phase synthesis; 3) Construction of a new automated oligosaccharide synthesizer; 4) Development of methods for the automated assembly of heparin and chondroitin sulfate oligosaccharides; 5) Synthesis of a collection of defined heparin and chondroitin sulfate oligosaccharides; 6) Construction of synthetic GAG microarrays and SPR; 7) Preparation of GAG dendrimers and quantum dots.
Project acronym B-PhosphoChem
Project Exploration of the 2D-Chemistry of Black Phosphorous
Researcher (PI) Andreas Hirsch
Summary We propose the development of the chemistry of black phosphorus (BP). B-PhosphoChem will constitute a new text book chapter in the realm of synthetic chemistry located at the interface of inorganic-, organic-, and materials chemistry as well as solid state physics. B-PhosphoChem will provide the basis for exciting and so far elusive applications such as ion batteries and stable high performance devices. Thin sheets of BP represent a new class of 2D materials and have recently raised tremendous interest in the scientific community. Outstanding physical properties such as high charge carrier mobility, combined with transparency and the persistence of a band gap have been discovered. However, the chemistry of BP remains still unexplored. B-PhosphoChem will close this gap and will a) provide the opportunity to modulate and fine tune the physical properties, b) allow for considerably improving the processability and increasing the solubility, c) establish concepts for the desired chemical stabilization, d) give access to the combination of BP properties with those of other compound classes, e) reveal the fundamental chemical properties and reactivity principles, and f) provide methods for establishing practical applications. Five work packages will be addressed: 1) Production of Thin Layer BP, 2) Supramolecular Chemistry of BP, 3) Intercalation Compounds of BP, 4) Covalent Chemistry of BP, and 5) BP-Based Materials and Devices. The work packages will be supported by systematic calculations. For our group, whose core competence is synthetic organic and supramolecular chemistry, the orientation towards inorganic phosphorus chemistry constitutes a major step into a completely new direction. However, we are convinced to be the most predestinated research group in the world successfully facing this challenge because of our leadership and well documented interdisciplinary experience in synthesizing and characterizing 0D-, 1D-, and 2D nanostructures.
We propose the development of the chemistry of black phosphorus (BP). B-PhosphoChem will constitute a new text book chapter in the realm of synthetic chemistry located at the interface of inorganic-, organic-, and materials chemistry as well as solid state physics. B-PhosphoChem will provide the basis for exciting and so far elusive applications such as ion batteries and stable high performance devices. Thin sheets of BP represent a new class of 2D materials and have recently raised tremendous interest in the scientific community. Outstanding physical properties such as high charge carrier mobility, combined with transparency and the persistence of a band gap have been discovered. However, the chemistry of BP remains still unexplored. B-PhosphoChem will close this gap and will a) provide the opportunity to modulate and fine tune the physical properties, b) allow for considerably improving the processability and increasing the solubility, c) establish concepts for the desired chemical stabilization, d) give access to the combination of BP properties with those of other compound classes, e) reveal the fundamental chemical properties and reactivity principles, and f) provide methods for establishing practical applications. Five work packages will be addressed: 1) Production of Thin Layer BP, 2) Supramolecular Chemistry of BP, 3) Intercalation Compounds of BP, 4) Covalent Chemistry of BP, and 5) BP-Based Materials and Devices. The work packages will be supported by systematic calculations. For our group, whose core competence is synthetic organic and supramolecular chemistry, the orientation towards inorganic phosphorus chemistry constitutes a major step into a completely new direction. However, we are convinced to be the most predestinated research group in the world successfully facing this challenge because of our leadership and well documented interdisciplinary experience in synthesizing and characterizing 0D-, 1D-, and 2D nanostructures.
Project acronym BEGMAT
Project Layered functional materials - beyond 'graphene'
Researcher (PI) Michael Janus Bojdys
Host Institution (HI) HUMBOLDT-UNIVERSITAET ZU BERLIN
Summary There is an apparent lack of non-metallic 2D-matrials for the construction of electronic devices, as only five materials of the "graphene family" are known: graphene, hBN, BCN, fluorographene, and graphene oxide – none of them with a narrow bandgap close to commercially used silicon. This ERC-StG proposal, BEGMAT, outlines a strategy for design, synthesis, and application of layered, functional materials that will go beyond this exclusive club. These materials "beyond graphene" (BEG) will have to meet – like graphene – the following criteria: (1) The BEG-materials will feature a transfer of crystalline order from the molecular (pm-range) to the macroscopic level (cm-range), (2) individual, free-standing layers of BEG-materials can be addressed by mechanical or chemical exfoliation, and (3) assemblies of different BEG-materials will be stacked as van der Waals heterostructures with unique properties. In contrast to the existing "graphene family", (4) BEG-materials will be constructed in a controlled way by covalent organic chemistry in a bottom-up approach from abundant precursors free of metals and critical raw materials (CRMs). Moreover – and unlike – many covalent organic frameworks (COFs), (5) BEG-materials will be fully aromatic, donor-acceptor systems to ensure that electronic properties can be addressed on macroscopic scale. The potential to make 2D materials "beyond graphene" is a great challenge to chemical bond formation and material design. In 2014 the applicant has demonstrated the feasibility of the concept to expand the "graphene family" with triazine-based graphitic carbon, a compound highlighted as an "emerging competitor for the miracle material" graphene. Now, the PI has the opportunity to build a full-scale research program on layered functional materials that offers unique insights into controlled, covalent linking-chemistry, and that addresses practicalities in device manufacture, and structure-properties relationships.
There is an apparent lack of non-metallic 2D-matrials for the construction of electronic devices, as only five materials of the "graphene family" are known: graphene, hBN, BCN, fluorographene, and graphene oxide – none of them with a narrow bandgap close to commercially used silicon. This ERC-StG proposal, BEGMAT, outlines a strategy for design, synthesis, and application of layered, functional materials that will go beyond this exclusive club. These materials "beyond graphene" (BEG) will have to meet – like graphene – the following criteria: (1) The BEG-materials will feature a transfer of crystalline order from the molecular (pm-range) to the macroscopic level (cm-range), (2) individual, free-standing layers of BEG-materials can be addressed by mechanical or chemical exfoliation, and (3) assemblies of different BEG-materials will be stacked as van der Waals heterostructures with unique properties. In contrast to the existing "graphene family", (4) BEG-materials will be constructed in a controlled way by covalent organic chemistry in a bottom-up approach from abundant precursors free of metals and critical raw materials (CRMs). Moreover – and unlike – many covalent organic frameworks (COFs), (5) BEG-materials will be fully aromatic, donor-acceptor systems to ensure that electronic properties can be addressed on macroscopic scale. The potential to make 2D materials "beyond graphene" is a great challenge to chemical bond formation and material design. In 2014 the applicant has demonstrated the feasibility of the concept to expand the "graphene family" with triazine-based graphitic carbon, a compound highlighted as an "emerging competitor for the miracle material" graphene. Now, the PI has the opportunity to build a full-scale research program on layered functional materials that offers unique insights into controlled, covalent linking-chemistry, and that addresses practicalities in device manufacture, and structure-properties relationships.
Project acronym BETACONTROL
Project Control of amyloid formation via beta-hairpin molecular recognition features
Researcher (PI) Wolfgang HOYER
Host Institution (HI) HEINRICH-HEINE-UNIVERSITAET DUESSELDORF
Summary The aggregation of proteins into amyloid fibrils is involved in various diseases which place a high burden on patients, families, caregivers, and healthcare systems, including Alzheimer's disease, Parkinson's disease and type 2 diabetes. While the therapeutic potential of the inhibition of amyloid formation and spreading has been recognized, there is a lack of effective strategies targeting the early steps of the aggregation reaction. In BETACONTROL, I want to establish a structure-guided approach to the control of amyloid formation and spreading. I will develop small molecule and polypeptide-based ligands that interfere with the initial phases of amyloid formation and thereby suppress any toxic oligomeric or fibrillar assemblies. The ligands will target beta-hairpin molecular recognition features, which I found to be readily accessible in disease-related amyloidogenic proteins. Targeting beta-hairpins enables retardation of protein aggregation by substoichiometric amounts of the ligand, affording inhibition of amyloid formation at low compound concentrations. As the strategy addresses the common propensity of amyloidogenic proteins to adopt beta-structure, it will be applicable to a wide range of proteins associated with various diseases. BETACONTROL will yield molecular-level insight into the mechanistic basis of amyloid formation and spreading. Furthermore, it will elucidate the significance of beta-hairpins as molecular recognition features in intrinsically disordered proteins (IDPs) and highlight the applicability of these features as targets for interference with protein-protein interactions of IDPs. Ultimately, BETACONTROL will provide a novel therapeutic approach to a range of devastating diseases.
The aggregation of proteins into amyloid fibrils is involved in various diseases which place a high burden on patients, families, caregivers, and healthcare systems, including Alzheimer's disease, Parkinson's disease and type 2 diabetes. While the therapeutic potential of the inhibition of amyloid formation and spreading has been recognized, there is a lack of effective strategies targeting the early steps of the aggregation reaction. In BETACONTROL, I want to establish a structure-guided approach to the control of amyloid formation and spreading. I will develop small molecule and polypeptide-based ligands that interfere with the initial phases of amyloid formation and thereby suppress any toxic oligomeric or fibrillar assemblies. The ligands will target beta-hairpin molecular recognition features, which I found to be readily accessible in disease-related amyloidogenic proteins. Targeting beta-hairpins enables retardation of protein aggregation by substoichiometric amounts of the ligand, affording inhibition of amyloid formation at low compound concentrations. As the strategy addresses the common propensity of amyloidogenic proteins to adopt beta-structure, it will be applicable to a wide range of proteins associated with various diseases. BETACONTROL will yield molecular-level insight into the mechanistic basis of amyloid formation and spreading. Furthermore, it will elucidate the significance of beta-hairpins as molecular recognition features in intrinsically disordered proteins (IDPs) and highlight the applicability of these features as targets for interference with protein-protein interactions of IDPs. Ultimately, BETACONTROL will provide a novel therapeutic approach to a range of devastating diseases.
Project acronym BIDECASEOX
Project Bio-inspired Design of Catalysts for Selective Oxidations of C-H and C=C Bonds
Researcher (PI) Miguel Costas Salgueiro
Host Institution (HI) UNIVERSITAT DE GIRONA
Summary The selective functionalization of C-H and C=C bonds remains a formidable unsolved problem, owing to their inert nature. Novel alkane and alkene oxidation reactions exhibiting good and/or unprecedented selectivities will have a big impact on bulk and fine chemistry by opening novel methodologies that will allow removal of protection-deprotection sequences, thus streamlining synthetic strategies. These goals are targeted in this project via design of iron and manganese catalysts inspired by structural elements of the active site of non-heme enzymes of the Rieske Dioxygenase family. Selectivity is pursued via rational design of catalysts that will exploit substrate recognition-exclusion phenomena, and control over proton and electron affinity of the active species. Moreover, these catalysts will employ H2O2 as oxidant, and will operate under mild conditions (pressure and temperature). The fundamental mechanistic aspects of the catalytic reactions, and the species implicated in C-H and C=C oxidation events will also be studied with the aim of building on the necessary knowledge to design future generations of catalysts, and provide models to understand the chemistry taking place in non-heme iron and manganese-dependent oxygenases.
The selective functionalization of C-H and C=C bonds remains a formidable unsolved problem, owing to their inert nature. Novel alkane and alkene oxidation reactions exhibiting good and/or unprecedented selectivities will have a big impact on bulk and fine chemistry by opening novel methodologies that will allow removal of protection-deprotection sequences, thus streamlining synthetic strategies. These goals are targeted in this project via design of iron and manganese catalysts inspired by structural elements of the active site of non-heme enzymes of the Rieske Dioxygenase family. Selectivity is pursued via rational design of catalysts that will exploit substrate recognition-exclusion phenomena, and control over proton and electron affinity of the active species. Moreover, these catalysts will employ H2O2 as oxidant, and will operate under mild conditions (pressure and temperature). The fundamental mechanistic aspects of the catalytic reactions, and the species implicated in C-H and C=C oxidation events will also be studied with the aim of building on the necessary knowledge to design future generations of catalysts, and provide models to understand the chemistry taking place in non-heme iron and manganese-dependent oxygenases.
Project acronym BioMet
Project Selective Functionalization of Saturated Hydrocarbons
Researcher (PI) Ilan MAREK
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Summary Despite that C–H functionalization represents a paradigm shift from the standard logic of organic synthesis, the selective activation of non-functionalized alkanes has puzzled chemists for centuries and is always referred to one of the remaining major challenges in chemical sciences. Alkanes are inert compounds representing the major constituents of natural gas and petroleum. Converting these cheap and widely available hydrocarbon feedstocks into added-value intermediates would tremendously affect the field of chemistry. For long saturated hydrocarbons, one must distinguish between non-equivalent but chemically very similar alkane substrate C−H bonds, and for functionalization at the terminus position, one must favor activation of the stronger, primary C−H bonds at the expense of weaker and numerous secondary C-H bonds. The goal of this work is to develop a general principle in organic synthesis for the preparation of a wide variety of more complex molecular architectures from saturated hydrocarbons. In our approach, the alkane will first be transformed into an alkene that will subsequently be engaged in a metal-catalyzed hydrometalation/migration sequence. The first step of the sequence, ideally represented by the removal of two hydrogen atoms, will be performed by the use of a mutated strain of Rhodococcus. The position and geometry of the formed double bond has no effect on the second step of the reaction as the metal-catalyzed hydrometalation/migration will isomerize the double bond along the carbon skeleton to selectively produce the primary organometallic species. Trapping the resulting organometallic derivatives with a large variety of electrophiles will provide the desired functionalized alkane. This work will lead to the invention of new, selective and efficient processes for the utilization of simple hydrocarbons and valorize the synthetic potential of raw hydrocarbon feedstock for the environmentally benign production of new compounds and new materials.
Despite that C–H functionalization represents a paradigm shift from the standard logic of organic synthesis, the selective activation of non-functionalized alkanes has puzzled chemists for centuries and is always referred to one of the remaining major challenges in chemical sciences. Alkanes are inert compounds representing the major constituents of natural gas and petroleum. Converting these cheap and widely available hydrocarbon feedstocks into added-value intermediates would tremendously affect the field of chemistry. For long saturated hydrocarbons, one must distinguish between non-equivalent but chemically very similar alkane substrate C−H bonds, and for functionalization at the terminus position, one must favor activation of the stronger, primary C−H bonds at the expense of weaker and numerous secondary C-H bonds. The goal of this work is to develop a general principle in organic synthesis for the preparation of a wide variety of more complex molecular architectures from saturated hydrocarbons. In our approach, the alkane will first be transformed into an alkene that will subsequently be engaged in a metal-catalyzed hydrometalation/migration sequence. The first step of the sequence, ideally represented by the removal of two hydrogen atoms, will be performed by the use of a mutated strain of Rhodococcus. The position and geometry of the formed double bond has no effect on the second step of the reaction as the metal-catalyzed hydrometalation/migration will isomerize the double bond along the carbon skeleton to selectively produce the primary organometallic species. Trapping the resulting organometallic derivatives with a large variety of electrophiles will provide the desired functionalized alkane. This work will lead to the invention of new, selective and efficient processes for the utilization of simple hydrocarbons and valorize the synthetic potential of raw hydrocarbon feedstock for the environmentally benign production of new compounds and new materials.
Project acronym BIONICS
Project Bio-Inspired Routes for Controlling the Structure and Properties of Materials: Reusing proven tricks on new materials
Researcher (PI) Boaz Pokroy
Summary "In the course of biomineralization, organisms produce a large variety of functional biogenic crystals that exhibit fascinating mechanical, optical, magnetic and other characteristics. More specifically, when living organisms grow crystals they can effectively control polymorph selection as well as the crystal morphology, shape, and even atomic structure. Materials existing in nature have extraordinary and specific functions, yet the materials employed in nature are quite different from those engineers would select. I propose to emulate specific strategies used by organisms in forming structural biogenic crystals, and to apply these strategies biomimetically so as to form new structural materials with new properties and characteristics. This bio-inspired approach will involve the adoption of three specific biological strategies. We believe that this procedure will open up new ways to control the structure and properties of smart materials. The three bio-inspired strategies that we will utilize are: (i) to control the short-range order of amorphous materials, making it possible to predetermine the polymorph obtained when they transform from the amorphous to the succeeding crystalline phase; (ii) to control the morphology of single crystals of various functional materials so that they can have intricate and curved surfaces and yet maintain their single-crystal nature; (iii) to entrap organic molecules into single crystals of functional materials so as to tailor and manipulate their electronic structure. The proposed research has significant potential for opening up new routes for the formation of novel functional materials. Specifically, it will make it possible for us (1) to produce single, intricately shaped crystals without the need to etch, drill or polish; (2) to control the short-range order of amorphous materials and hence the polymorph of the successive crystalline phase; (3) to tune the band gap of semiconductors via incorporation of tailored bio-molecules."
"In the course of biomineralization, organisms produce a large variety of functional biogenic crystals that exhibit fascinating mechanical, optical, magnetic and other characteristics. More specifically, when living organisms grow crystals they can effectively control polymorph selection as well as the crystal morphology, shape, and even atomic structure. Materials existing in nature have extraordinary and specific functions, yet the materials employed in nature are quite different from those engineers would select. I propose to emulate specific strategies used by organisms in forming structural biogenic crystals, and to apply these strategies biomimetically so as to form new structural materials with new properties and characteristics. This bio-inspired approach will involve the adoption of three specific biological strategies. We believe that this procedure will open up new ways to control the structure and properties of smart materials. The three bio-inspired strategies that we will utilize are: (i) to control the short-range order of amorphous materials, making it possible to predetermine the polymorph obtained when they transform from the amorphous to the succeeding crystalline phase; (ii) to control the morphology of single crystals of various functional materials so that they can have intricate and curved surfaces and yet maintain their single-crystal nature; (iii) to entrap organic molecules into single crystals of functional materials so as to tailor and manipulate their electronic structure. The proposed research has significant potential for opening up new routes for the formation of novel functional materials. Specifically, it will make it possible for us (1) to produce single, intricately shaped crystals without the need to etch, drill or polish; (2) to control the short-range order of amorphous materials and hence the polymorph of the successive crystalline phase; (3) to tune the band gap of semiconductors via incorporation of tailored bio-molecules."
Project acronym BioSilica
Project Materials synthesis in vivo – intracellular formation of nanostructured silica by microalgae
Researcher (PI) Assaf GAL
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Summary Organisms evolved the ability to form a magnificent array of functional materials, which surpass any man-made product. A prominent example is diatoms, marine microalgae that form an intricate cell-wall made of meso-porous silica. Diatom silica is a tough, hierarchically built, and biocompatible material that is environmentally friendly and cheap, making it an exciting target for nanotechnology. Nevertheless, the principles of this regulated formation mechanism remain elusive. A persistent obstacle for elucidating biomineralization processes is the inaccessibility of the cellular environment for structural and chemical investigations. Recently, far-reaching developments in electron microscopy have revolutionized our abilities to investigate chemical processes inside living organisms. It is now becoming feasible to image and analyze, with nanometer-scale resolution, an intracellular mineralization process. This proposal aims to elucidate the intracellular mechanism of silica formation by diatoms. We will study cells undergoing the silicification process in situ, using a suite of state-of-the-art electron and X-ray imaging and spectroscopy tools. The combination of structural and chemical data will enable us to elucidate: 1) The concentration and stabilization mechanism of transient Si phases in the cell. 2) The nanoscale environment in which silica condensation takes place. 3) Genetic and environmental strategies to engineer the silicification process for designed outcomes. Diatom silica is a promising material for applications such as photonics, pharmaceuticals, and catalysis, which require hierarchical, high-surface area, nano-materials. The achievements of this project will inspire synthetic methodologies to produce and design nano-patterned silica, and genetically-engineer the biological silicification process to produce custom-made materials.
Organisms evolved the ability to form a magnificent array of functional materials, which surpass any man-made product. A prominent example is diatoms, marine microalgae that form an intricate cell-wall made of meso-porous silica. Diatom silica is a tough, hierarchically built, and biocompatible material that is environmentally friendly and cheap, making it an exciting target for nanotechnology. Nevertheless, the principles of this regulated formation mechanism remain elusive. A persistent obstacle for elucidating biomineralization processes is the inaccessibility of the cellular environment for structural and chemical investigations. Recently, far-reaching developments in electron microscopy have revolutionized our abilities to investigate chemical processes inside living organisms. It is now becoming feasible to image and analyze, with nanometer-scale resolution, an intracellular mineralization process. This proposal aims to elucidate the intracellular mechanism of silica formation by diatoms. We will study cells undergoing the silicification process in situ, using a suite of state-of-the-art electron and X-ray imaging and spectroscopy tools. The combination of structural and chemical data will enable us to elucidate: 1) The concentration and stabilization mechanism of transient Si phases in the cell. 2) The nanoscale environment in which silica condensation takes place. 3) Genetic and environmental strategies to engineer the silicification process for designed outcomes. Diatom silica is a promising material for applications such as photonics, pharmaceuticals, and catalysis, which require hierarchical, high-surface area, nano-materials. The achievements of this project will inspire synthetic methodologies to produce and design nano-patterned silica, and genetically-engineer the biological silicification process to produce custom-made materials.
Project acronym BORYLENEFUN
Project The versatile metal-boron multiple bond: application of borylenes to metathesis, catalysis, and macromolecules
Researcher (PI) Holger Christoph Braunschweig
Host Institution (HI) JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Summary Borylated molecules and polymers are of great interest due to their broad application in organic synthesis and materials science. The functionalisation of organic substrates with boryl groups R2B is based on classical synthetic methods e.g. hydro- and diboration of C-C multiple bonds. Likewise, borylenes B-R should be versatile reagents for corresponding functionalisations, however, the chemistry of such species remained unexplored due to their high instability. Pioneering work in our laboratories has proven that complexes of the type [LxM=B-R] not only stabilise elusive borylenes B-R in the coordination sphere of various transition metals but, more importantly, serve as unprecedented sources for these species under ambient conditions in condensed phase. Thus, the major objective of the current proposal is to establish novel reactivity patterns based on B-R fragments for the functionalisation of organometallic and organic substrates. Particular attention will be paid to the synthesis of novel molecular and polymeric species with significant potential as materials. Given the pronounced importance of boron containing species in organic synthesis, catalysis and materials science, the proposed project is expected to have a significant impact on these areas of applied molecular science. In addition, a wide range of fundamental aspects will be covered, targeting e.g. novel conjugated cyclic systems or molecules with unprecedented boron-element combinations. The following subjects will be pursued: 1)Cationic and anionic dimetalloborylenes as complementary building blocks in synthesis 2)Application of borylene metathesis in stoichiometric and catalytic transformations 3)Borylene transfer for organometallic synthesis and borylene based pi-conjugated materials
Borylated molecules and polymers are of great interest due to their broad application in organic synthesis and materials science. The functionalisation of organic substrates with boryl groups R2B is based on classical synthetic methods e.g. hydro- and diboration of C-C multiple bonds. Likewise, borylenes B-R should be versatile reagents for corresponding functionalisations, however, the chemistry of such species remained unexplored due to their high instability. Pioneering work in our laboratories has proven that complexes of the type [LxM=B-R] not only stabilise elusive borylenes B-R in the coordination sphere of various transition metals but, more importantly, serve as unprecedented sources for these species under ambient conditions in condensed phase. Thus, the major objective of the current proposal is to establish novel reactivity patterns based on B-R fragments for the functionalisation of organometallic and organic substrates. Particular attention will be paid to the synthesis of novel molecular and polymeric species with significant potential as materials. Given the pronounced importance of boron containing species in organic synthesis, catalysis and materials science, the proposed project is expected to have a significant impact on these areas of applied molecular science. In addition, a wide range of fundamental aspects will be covered, targeting e.g. novel conjugated cyclic systems or molecules with unprecedented boron-element combinations. The following subjects will be pursued: 1)Cationic and anionic dimetalloborylenes as complementary building blocks in synthesis 2)Application of borylene metathesis in stoichiometric and catalytic transformations 3)Borylene transfer for organometallic synthesis and borylene based pi-conjugated materials
Project acronym BOTTOM-UP_SYSCHEM
Project Systems Chemistry from Bottom Up: Switching, Gating and Oscillations in Non Enzymatic Peptide Networks
Researcher (PI) Gonen Ashkenasy
Host Institution (HI) BEN-GURION UNIVERSITY OF THE NEGEV
Summary The study of synthetic molecular networks is of fundamental importance for understanding the organizational principles of biological systems and may well be the key to unraveling the origins of life. In addition, such systems may be useful for parallel synthesis of molecules, implementation of catalysis via multi-step pathways, and as media for various applications in nano-medicine and nano-electronics. We have been involved recently in developing peptide-based replicating networks and revealed their dynamic characteristics. We argue here that the structural information embedded in the polypeptide chains is sufficiently rich to allow the construction of peptide 'Systems Chemistry', namely, to facilitate the use of replicating networks as cell-mimetics, featuring complex dynamic behavior. To bring this novel idea to reality, we plan to take a unique holistic approach by studying such networks both experimentally and via simulations, for elucidating basic-principles and towards applications in adjacent fields, such as molecular electronics. Towards realizing these aims, we will study three separate but inter-related objectives: (i) design and characterization of networks that react and rewire in response to external triggers, such as light, (ii) design of networks that operate via new dynamic rules of product formation that lead to oscillations, and (iii) exploitation of the molecular information gathered from the networks as means to control switching and gating in molecular electronic devices. We believe that achieving the project's objectives will be highly significant for the development of the arising field of Systems Chemistry, and in addition will provide valuable tools for studying related scientific fields, such as systems biology and molecular electronics.
The study of synthetic molecular networks is of fundamental importance for understanding the organizational principles of biological systems and may well be the key to unraveling the origins of life. In addition, such systems may be useful for parallel synthesis of molecules, implementation of catalysis via multi-step pathways, and as media for various applications in nano-medicine and nano-electronics. We have been involved recently in developing peptide-based replicating networks and revealed their dynamic characteristics. We argue here that the structural information embedded in the polypeptide chains is sufficiently rich to allow the construction of peptide 'Systems Chemistry', namely, to facilitate the use of replicating networks as cell-mimetics, featuring complex dynamic behavior. To bring this novel idea to reality, we plan to take a unique holistic approach by studying such networks both experimentally and via simulations, for elucidating basic-principles and towards applications in adjacent fields, such as molecular electronics. Towards realizing these aims, we will study three separate but inter-related objectives: (i) design and characterization of networks that react and rewire in response to external triggers, such as light, (ii) design of networks that operate via new dynamic rules of product formation that lead to oscillations, and (iii) exploitation of the molecular information gathered from the networks as means to control switching and gating in molecular electronic devices. We believe that achieving the project's objectives will be highly significant for the development of the arising field of Systems Chemistry, and in addition will provide valuable tools for studying related scientific fields, such as systems biology and molecular electronics.
Project acronym C-H ACTIVATION
Project New Concepts for Utilizing a Ubiquitous (Non-)Functional Group - C-H Bond Activation for Increased Efficiency in Organic Synthesis
Researcher (PI) Frank Klaus Glorius
Host Institution (HI) WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER
Summary C-H activations and related reactions can potentially revolutionize the way organic molecules are made and allow a more efficient use of earth's natural resources. Despite the rapid progress of the last couple of years, many problems like limited scope, extreme reaction conditions (temperature, excess of reagents) or low reactivities and selectivities remain in many cases. In this comprehensive proposal containing a number of projects and work packages, we want to develope new C-H activation methods 1) for the efficient synthesis of heterocycles, 2) for the activation of unactivated C(sp3)-H bonds, 3) by employing newly designed Fe-NHC complexes and 4) demonstrating the application of C-H activation for the functionalization of metal-organic frameworks (MOFs). The realization of these goals would render organic synthesis greener and more efficient and would have an impact on the preparation of compounds in academia and industry.
C-H activations and related reactions can potentially revolutionize the way organic molecules are made and allow a more efficient use of earth's natural resources. Despite the rapid progress of the last couple of years, many problems like limited scope, extreme reaction conditions (temperature, excess of reagents) or low reactivities and selectivities remain in many cases. In this comprehensive proposal containing a number of projects and work packages, we want to develope new C-H activation methods 1) for the efficient synthesis of heterocycles, 2) for the activation of unactivated C(sp3)-H bonds, 3) by employing newly designed Fe-NHC complexes and 4) demonstrating the application of C-H activation for the functionalization of metal-organic frameworks (MOFs). The realization of these goals would render organic synthesis greener and more efficient and would have an impact on the preparation of compounds in academia and industry.
Project acronym CABUM
Project An investigation of the mechanisms at the interaction between cavitation bubbles and contaminants
Researcher (PI) Matevz DULAR
Host Institution (HI) UNIVERZA V LJUBLJANI
Summary A sudden decrease in pressure triggers the formation of vapour and gas bubbles inside a liquid medium (also called cavitation). This leads to many (key) engineering problems: material loss, noise and vibration of hydraulic machinery. On the other hand, cavitation is a potentially a useful phenomenon: the extreme conditions are increasingly used for a wide variety of applications such as surface cleaning, enhanced chemistry, and waste water treatment (bacteria eradication and virus inactivation). Despite this significant progress a large gap persists between the understanding of the mechanisms that contribute to the effects of cavitation and its application. Although engineers are already commercializing devices that employ cavitation, we are still not able to answer the fundamental question: What precisely are the mechanisms how bubbles can clean, disinfect, kill bacteria and enhance chemical activity? The overall objective of the project is to understand and determine the fundamental physics of the interaction of cavitation bubbles with different contaminants. To address this issue, the CABUM project will investigate the physical background of cavitation from physical, biological and engineering perspective on three complexity scales: i) on single bubble level, ii) on organised and iii) on random bubble clusters, producing a progressive multidisciplinary synergetic effect. The proposed synergetic approach builds on the PI's preliminary research and employs novel experimental and numerical methodologies, some of which have been developed by the PI and his research group, to explore the physics of cavitation behaviour in interaction with bacteria and viruses. Understanding the fundamental physical background of cavitation in interaction with contaminants will have a ground-breaking implications in various scientific fields (engineering, chemistry and biology) and will, in the future, enable the exploitation of cavitation in water and soil treatment processes.
A sudden decrease in pressure triggers the formation of vapour and gas bubbles inside a liquid medium (also called cavitation). This leads to many (key) engineering problems: material loss, noise and vibration of hydraulic machinery. On the other hand, cavitation is a potentially a useful phenomenon: the extreme conditions are increasingly used for a wide variety of applications such as surface cleaning, enhanced chemistry, and waste water treatment (bacteria eradication and virus inactivation). Despite this significant progress a large gap persists between the understanding of the mechanisms that contribute to the effects of cavitation and its application. Although engineers are already commercializing devices that employ cavitation, we are still not able to answer the fundamental question: What precisely are the mechanisms how bubbles can clean, disinfect, kill bacteria and enhance chemical activity? The overall objective of the project is to understand and determine the fundamental physics of the interaction of cavitation bubbles with different contaminants. To address this issue, the CABUM project will investigate the physical background of cavitation from physical, biological and engineering perspective on three complexity scales: i) on single bubble level, ii) on organised and iii) on random bubble clusters, producing a progressive multidisciplinary synergetic effect. The proposed synergetic approach builds on the PI's preliminary research and employs novel experimental and numerical methodologies, some of which have been developed by the PI and his research group, to explore the physics of cavitation behaviour in interaction with bacteria and viruses. Understanding the fundamental physical background of cavitation in interaction with contaminants will have a ground-breaking implications in various scientific fields (engineering, chemistry and biology) and will, in the future, enable the exploitation of cavitation in water and soil treatment processes.
Project acronym CADENCE
Project Catalytic Dual-Function Devices Against Cancer
Researcher (PI) Jesus Santamaria
Host Institution (HI) UNIVERSIDAD DE ZARAGOZA
Summary Despite intense research efforts in almost every branch of the natural sciences, cancer continues to be one of the leading causes of death worldwide. It is thus remarkable that little or no therapeutic use has been made of a whole discipline, heterogeneous catalysis, which is noted for its specificity and for enabling chemical reactions in otherwise passive environments. At least in part, this could be attributed to practical difficulties: the selective delivery of a catalyst to a tumour and the remote activation of its catalytic function only after it has reached its target are highly challenging objectives. Only recently, the necessary tools to overcome these problems seem within reach. CADENCE aims for a breakthrough in cancer therapy by developing a new therapeutic concept. The central hypothesis is that a growing tumour can be treated as a special type of reactor in which reaction conditions can be tailored to achieve two objectives: i) molecules essential to tumour growth are locally depleted and ii) toxic, short-lived products are generated in situ. To implement this novel approach we will make use of core concepts of reactor engineering (kinetics, heat and mass transfer, catalyst design), as well as of ideas borrowed from other areas, mainly those of bio-orthogonal chemistry and controlled drug delivery. We will explore two different strategies (classical EPR effect and stem cells as Trojan Horses) to deliver optimized catalysts to the tumour. Once the catalysts have reached the tumour they will be remotely activated using near-infrared (NIR) light, that affords the highest penetration into body tissues. This is an ambitious project, addressing all the key steps from catalyst design to in vivo studies. Given the novel perspective provided by CADENCE, even partial success in any of the approaches to be tested would have a significant impact on the therapeutic toolbox available to treat cancer.
Despite intense research efforts in almost every branch of the natural sciences, cancer continues to be one of the leading causes of death worldwide. It is thus remarkable that little or no therapeutic use has been made of a whole discipline, heterogeneous catalysis, which is noted for its specificity and for enabling chemical reactions in otherwise passive environments. At least in part, this could be attributed to practical difficulties: the selective delivery of a catalyst to a tumour and the remote activation of its catalytic function only after it has reached its target are highly challenging objectives. Only recently, the necessary tools to overcome these problems seem within reach. CADENCE aims for a breakthrough in cancer therapy by developing a new therapeutic concept. The central hypothesis is that a growing tumour can be treated as a special type of reactor in which reaction conditions can be tailored to achieve two objectives: i) molecules essential to tumour growth are locally depleted and ii) toxic, short-lived products are generated in situ. To implement this novel approach we will make use of core concepts of reactor engineering (kinetics, heat and mass transfer, catalyst design), as well as of ideas borrowed from other areas, mainly those of bio-orthogonal chemistry and controlled drug delivery. We will explore two different strategies (classical EPR effect and stem cells as Trojan Horses) to deliver optimized catalysts to the tumour. Once the catalysts have reached the tumour they will be remotely activated using near-infrared (NIR) light, that affords the highest penetration into body tissues. This is an ambitious project, addressing all the key steps from catalyst design to in vivo studies. Given the novel perspective provided by CADENCE, even partial success in any of the approaches to be tested would have a significant impact on the therapeutic toolbox available to treat cancer.
Project acronym CAMBAT
Project Calcium and magnesium metal anode based batteries
Researcher (PI) Alexandre PONROUCH
Summary Li-ion battery is ubiquitous and has emerged as the major contender to power electric vehicles, yet Li-ion is slowly but surely reaching its limits and controversial debates on lithium supply cannot be ignored. New sustainable battery chemistries must be developed and the most appealing alternatives are to use Ca or Mg metal anodes which would bring a breakthrough in terms of energy density relying on much more abundant elements. Since Mg and Ca do not appear to be plagued by dendrite formation like Li, metal anodes could thus safely be used. While standard electrolytes forming stable passivation layers at the electrode/electrolyte interfaces enabled the success of the Li-ion technology, the migration of divalent cations through a passivation layer was thought to be impossible. Thus, all research efforts to date have been devoted to the formulation of electrolytes that do not form such layer. This approach comes with complex electrolyte, highly corrosive and with narrow electrochemical stability window leading to incompatibility with high voltage cathodes thus penalizing energy density. The applicant demonstrated that calcium can be reversibly plated and stripped through a stable passivation layer when transport properties within the electrolyte are tuned (decreasing ion pair formation). CAMBAT aims at developing new electrolytes forming stable passivation layers and allowing the migration of Ca2+ and Mg2+. Such a dramatic shift in the methodology would allow considering a completely new family of electrolytes enabling the evaluation of high voltage cathode materials that cannot be tested in the electrolytes available nowadays. 1Ah prototype cells will be assembled as proof of concept, targets for energy density and cost being ca. 300 Wh/kg and 250 $/kWh, respectively, thus doubling the energy density while dividing by at least a factor of 2 the price when compared to state of the art Li-ion batteries and having the potential for being SAFER (absence of dendrite).
Li-ion battery is ubiquitous and has emerged as the major contender to power electric vehicles, yet Li-ion is slowly but surely reaching its limits and controversial debates on lithium supply cannot be ignored. New sustainable battery chemistries must be developed and the most appealing alternatives are to use Ca or Mg metal anodes which would bring a breakthrough in terms of energy density relying on much more abundant elements. Since Mg and Ca do not appear to be plagued by dendrite formation like Li, metal anodes could thus safely be used. While standard electrolytes forming stable passivation layers at the electrode/electrolyte interfaces enabled the success of the Li-ion technology, the migration of divalent cations through a passivation layer was thought to be impossible. Thus, all research efforts to date have been devoted to the formulation of electrolytes that do not form such layer. This approach comes with complex electrolyte, highly corrosive and with narrow electrochemical stability window leading to incompatibility with high voltage cathodes thus penalizing energy density. The applicant demonstrated that calcium can be reversibly plated and stripped through a stable passivation layer when transport properties within the electrolyte are tuned (decreasing ion pair formation). CAMBAT aims at developing new electrolytes forming stable passivation layers and allowing the migration of Ca2+ and Mg2+. Such a dramatic shift in the methodology would allow considering a completely new family of electrolytes enabling the evaluation of high voltage cathode materials that cannot be tested in the electrolytes available nowadays. 1Ah prototype cells will be assembled as proof of concept, targets for energy density and cost being ca. 300 Wh/kg and 250 $/kWh, respectively, thus doubling the energy density while dividing by at least a factor of 2 the price when compared to state of the art Li-ion batteries and having the potential for being SAFER (absence of dendrite).
Project acronym CATA-LUX
Project Light-Driven Asymmetric Organocatalysis
Researcher (PI) Paolo Melchiorre
Host Institution (HI) FUNDACIO PRIVADA INSTITUT CATALA D'INVESTIGACIO QUIMICA
Summary Visible light photocatalysis and metal-free organocatalytic processes are powerful strategies of modern chemical research with extraordinary potential for the sustainable preparation of organic molecules. However, these environmentally respectful approaches have to date remained largely unrelated. The proposed research seeks to merge these fields of molecule activation to redefine their synthetic potential. Light-driven processes considerably enrich the modern synthetic repertoire, offering a potent way to build complex organic frameworks. In contrast, it is extremely challenging to develop asymmetric catalytic photoreactions that can create chiral molecules with a well-defined three-dimensional arrangement. By developing innovative methodologies to effectively address this issue, I will provide a novel reactivity framework for conceiving light-driven enantioselective organocatalytic processes. I will translate the effective tools governing the success of ground state asymmetric organocatalysis into the realm of photochemical reactivity, exploiting the potential of key organocatalytic intermediates to directly participate in the photoexcitation of substrates. At the same time, the chiral organocatalyst will ensure effective stereochemical control. This single catalyst system, where stereoinduction and photoactivation merge in a sole organocatalyst, will serve for developing novel enantioselective photoreactions. In a complementary dual catalytic approach, the synergistic activities of an organocatalyst and a metal-free photosensitiser will combine to realise asymmetric variants of venerable photochemical processes, which have never before succumbed to a stereocontrolled approach. This proposal challenges the current perception that photochemistry is too unselective to parallel the impressive levels of efficiency reached by the asymmetric catalysis of thermal reactions, expanding the way chemists think about making chiral molecules
Visible light photocatalysis and metal-free organocatalytic processes are powerful strategies of modern chemical research with extraordinary potential for the sustainable preparation of organic molecules. However, these environmentally respectful approaches have to date remained largely unrelated. The proposed research seeks to merge these fields of molecule activation to redefine their synthetic potential. Light-driven processes considerably enrich the modern synthetic repertoire, offering a potent way to build complex organic frameworks. In contrast, it is extremely challenging to develop asymmetric catalytic photoreactions that can create chiral molecules with a well-defined three-dimensional arrangement. By developing innovative methodologies to effectively address this issue, I will provide a novel reactivity framework for conceiving light-driven enantioselective organocatalytic processes. I will translate the effective tools governing the success of ground state asymmetric organocatalysis into the realm of photochemical reactivity, exploiting the potential of key organocatalytic intermediates to directly participate in the photoexcitation of substrates. At the same time, the chiral organocatalyst will ensure effective stereochemical control. This single catalyst system, where stereoinduction and photoactivation merge in a sole organocatalyst, will serve for developing novel enantioselective photoreactions. In a complementary dual catalytic approach, the synergistic activities of an organocatalyst and a metal-free photosensitiser will combine to realise asymmetric variants of venerable photochemical processes, which have never before succumbed to a stereocontrolled approach. This proposal challenges the current perception that photochemistry is too unselective to parallel the impressive levels of efficiency reached by the asymmetric catalysis of thermal reactions, expanding the way chemists think about making chiral molecules
Project acronym CatCHFun
Project Sustainable Catalytic C-H Bond Functionalization
Researcher (PI) Lutz Ackermann
Host Institution (HI) GEORG-AUGUST-UNIVERSITAT GOTTINGENSTIFTUNG OFFENTLICHEN RECHTS
Summary The impressive progress in synthetic organic chemistry during the past century has propelled this discipline to its current central place as the key enabling technology in the physical and life sciences. Despite these remarkable advances, our ability to construct molecules of even moderate structural complexity remains unsatisfactory, since these syntheses continue to be inefficient, rely on a high number of reaction steps, and generate undesired, often toxic waste. These features led to the general need for greener transformations that will stimulate the development of more sustainable chemical industries. Conventional approaches in synthetic organic chemistry make use of starting materials displaying specific functional groups, the installation of which results in costly reaction and purification steps. Therefore, an environmentally-sound and economically-attractive alternative is represented by the direct functionalization of ubiquitous carbon-hydrogen (C–H) bonds. These transition-metal-catalyzed processes avoid prefunctionalization strategies, prevent the formation of undesired waste, and thus enable an overall streamlining of organic synthesis. While considerable recent progress has been accomplished in C–H bond functionalizations, available methodologies continue to be limited in scope, and key challenges are still to be overcome. Establishing a full set of sustainable C–H bond functionalization protocols will undeniably have a tremendous impact on various applied areas, such as drug discovery, chemical industries or material sciences.
The impressive progress in synthetic organic chemistry during the past century has propelled this discipline to its current central place as the key enabling technology in the physical and life sciences. Despite these remarkable advances, our ability to construct molecules of even moderate structural complexity remains unsatisfactory, since these syntheses continue to be inefficient, rely on a high number of reaction steps, and generate undesired, often toxic waste. These features led to the general need for greener transformations that will stimulate the development of more sustainable chemical industries. Conventional approaches in synthetic organic chemistry make use of starting materials displaying specific functional groups, the installation of which results in costly reaction and purification steps. Therefore, an environmentally-sound and economically-attractive alternative is represented by the direct functionalization of ubiquitous carbon-hydrogen (C–H) bonds. These transition-metal-catalyzed processes avoid prefunctionalization strategies, prevent the formation of undesired waste, and thus enable an overall streamlining of organic synthesis. While considerable recent progress has been accomplished in C–H bond functionalizations, available methodologies continue to be limited in scope, and key challenges are still to be overcome. Establishing a full set of sustainable C–H bond functionalization protocols will undeniably have a tremendous impact on various applied areas, such as drug discovery, chemical industries or material sciences.
Project acronym CATGOLD
Project ADVANCING GOLD CATALYSIS
Researcher (PI) Antonio María Echavarren Pablos
Summary We plan to chase new goals by exploring the limits of gold chemistry and organic synthesis. A major goal is to promote copper to the level of gold as the catalyst of choice for the activation of alkynes under homogeneous conditions. Another major goal is to develop enantioselective reactions based on a new chiral catalyst design to overcome the inherent limitations of the linear coordination of d10 M(I) coinage metals. We whish to contribute to bridge the gap between homogeneous and heterogeneous gold catalysis discovering new reactions for C-C bond formation via cross-coupling and C-H activation. We will apply new methods based on Au catalysis to fill the gap that exists between chemical synthesis and physical methods such as graphite exfoliation or laser ablation for the synthesis of nanographenes and other large acenes.
We plan to chase new goals by exploring the limits of gold chemistry and organic synthesis. A major goal is to promote copper to the level of gold as the catalyst of choice for the activation of alkynes under homogeneous conditions. Another major goal is to develop enantioselective reactions based on a new chiral catalyst design to overcome the inherent limitations of the linear coordination of d10 M(I) coinage metals. We whish to contribute to bridge the gap between homogeneous and heterogeneous gold catalysis discovering new reactions for C-C bond formation via cross-coupling and C-H activation. We will apply new methods based on Au catalysis to fill the gap that exists between chemical synthesis and physical methods such as graphite exfoliation or laser ablation for the synthesis of nanographenes and other large acenes.
Project acronym CaTs n DOCs
Project Chemically and Thermally Stable Nano-sized Discrete Organic Cage Compounds
Researcher (PI) Michael Günther MASTALERZ
Summary Shape-persistent organic cage compounds consisting only of covalent bonds are fascinating synthetically targets, because they are studied as hosts for the selective recognition of guest molecules, such as artificial lectins, for catalysis in confined space or for the construction of a new type of porous material. For the latter, the shape-persistency and rigidity of the cage cavity is of utmost importance. There are in principle two existing strategies for the synthesis of shape-persistent organic cage compounds. Strategy I: A stepwise approach by irreversible reactions. Here, the advantage is the chemical stability of the target compound due to the intrinsic stabilities of the formed bonds. The disadvantage of this approach is in general the low overall yield, because the system does not allow any 'self-correction' of once formed bonds. This is different for the other approach used in Strategy II: By using dynamic covalent bond formation as synthetic tool, shape-persistent organic cages can be constructed from rather simple molecular building blocks in one step. Here, the yields are usually very high or even quantitatively, because the reversibility of the reaction allows the system to self-correct. Unfortunately, the resulting compounds are more prone to chemical cleavage of the cages than those synthesized by the irreversible approach. Within this project, we will combine the advantages of both strategies to synthesize chemically and thermally stable nano-sized discrete organic cage compounds in a two-step approach in high yields. To demonstrate the versatility and synthetic power of this approach, pure hydrocarbon cages will be synthesized in a few steps in high yields. Finally, this strategy will make for the first time open and closed-shell fullerenes and heterofullerenes that are isomerically pure, accessible.
Shape-persistent organic cage compounds consisting only of covalent bonds are fascinating synthetically targets, because they are studied as hosts for the selective recognition of guest molecules, such as artificial lectins, for catalysis in confined space or for the construction of a new type of porous material. For the latter, the shape-persistency and rigidity of the cage cavity is of utmost importance. There are in principle two existing strategies for the synthesis of shape-persistent organic cage compounds. Strategy I: A stepwise approach by irreversible reactions. Here, the advantage is the chemical stability of the target compound due to the intrinsic stabilities of the formed bonds. The disadvantage of this approach is in general the low overall yield, because the system does not allow any 'self-correction' of once formed bonds. This is different for the other approach used in Strategy II: By using dynamic covalent bond formation as synthetic tool, shape-persistent organic cages can be constructed from rather simple molecular building blocks in one step. Here, the yields are usually very high or even quantitatively, because the reversibility of the reaction allows the system to self-correct. Unfortunately, the resulting compounds are more prone to chemical cleavage of the cages than those synthesized by the irreversible approach. Within this project, we will combine the advantages of both strategies to synthesize chemically and thermally stable nano-sized discrete organic cage compounds in a two-step approach in high yields. To demonstrate the versatility and synthetic power of this approach, pure hydrocarbon cages will be synthesized in a few steps in high yields. Finally, this strategy will make for the first time open and closed-shell fullerenes and heterofullerenes that are isomerically pure, accessible.
Project acronym CHAOS
Project C-H Acids for Organic Synthesis
Researcher (PI) Benjamin List
Host Institution (HI) MAX PLANCK INSTITUT FUER KOHLENFORSCHUNG
Summary Enantioselective Brønsted acid organocatalysis has the potential to revolutionize asymmetric synthesis. However, the commonly used chiral phosphoric acid catalysts are typically limited to certain, fairly reactive substrate classes such as imines. Recently, more active and stereoselective catalysts have been introduced, which rely on acidic N–H bonds, and which have significantly widened the scope of suitable substrates. Despite the considerable success of these catalysts, however, several important and highly attractive substrate classes still remain out of reach. The applicant's group has now identified C–H acids as novel and highly promising candidates to tackle these long standing challenges. Here, a research program with three major goals is proposed: 1) broadly conceived synthetic studies will be undertaken, which are expected to give access to C–H acids with a wide range of acidity and steric confinement. 2) These C–H acids will be applied to address one of the most general limitations currently encountered in organocatalysis: The enantioselective conversion of small and unbiased substrates. 3) The developed C–H acids, which are expected to enable unprecedented acidities and catalytic activities, will be employed in the activation of increasingly less reactive electrophiles, for example aliphatic aldehydes but also esters and olefins, for which enantioselective organocatalytic reactions are currently very limited or even unknown. Overall, this research program will aim at the design, synthesis and application of C–H acids as platform for solving several long standing challenges in asymmetric organocatalysis. The introduction of C–H acids for organic synthesis is expected to enrich the toolbox of synthetic chemists in both academic and industrial laboratories.
Enantioselective Brønsted acid organocatalysis has the potential to revolutionize asymmetric synthesis. However, the commonly used chiral phosphoric acid catalysts are typically limited to certain, fairly reactive substrate classes such as imines. Recently, more active and stereoselective catalysts have been introduced, which rely on acidic N–H bonds, and which have significantly widened the scope of suitable substrates. Despite the considerable success of these catalysts, however, several important and highly attractive substrate classes still remain out of reach. The applicant's group has now identified C–H acids as novel and highly promising candidates to tackle these long standing challenges. Here, a research program with three major goals is proposed: 1) broadly conceived synthetic studies will be undertaken, which are expected to give access to C–H acids with a wide range of acidity and steric confinement. 2) These C–H acids will be applied to address one of the most general limitations currently encountered in organocatalysis: The enantioselective conversion of small and unbiased substrates. 3) The developed C–H acids, which are expected to enable unprecedented acidities and catalytic activities, will be employed in the activation of increasingly less reactive electrophiles, for example aliphatic aldehydes but also esters and olefins, for which enantioselective organocatalytic reactions are currently very limited or even unknown. Overall, this research program will aim at the design, synthesis and application of C–H acids as platform for solving several long standing challenges in asymmetric organocatalysis. The introduction of C–H acids for organic synthesis is expected to enrich the toolbox of synthetic chemists in both academic and industrial laboratories.
Project acronym chem-fs-MOF
Project Chemical Engineering of Functional Stable Metal-Organic Frameworks: Porous Crystals and Thin Film Devices
Researcher (PI) Carlos MARTI-GASTALDO
Summary Metal-Organic-Frameworks (MOFs) offer appealing advantages over classical solids from combination of high surface areas with the crystallinity of inorganic materials and the synthetic versatility (unlimited combination of metals and linkers for fine tuning of properties) and processability of organic materials. Provided chemical stability, I expect combination of porosity with manipulable electrical and optical properties to open a new world of possibilities, with MOFs playing an emerging role in fields of key environmental value like photovoltaics, photocatalysis or electrocatalysis. The conventional insulating character of MOFs and their poor chemical stability (only a minimum fraction are hydrolytically stable) are arguably the two key limitations hindering further development in this context. With chem-fs-MOF I expect to deliver: 1. New synthetic routes specifically designed for producing new, hydrolytically stable Fe(III) and Ti(IV)-MOFs (new synthetic platforms for new materials). 2. More advanced crystalline materials to feature tunable function by chemical manipulation of MOF's optical/electrical properties and pore activity (function-led chemical engineering). 3. High-quality ultrathin films, reliant on the transfer of single-layers, alongside establishing the techniques required for evaluating their electric properties (key to device integration). Recent works on graphene and layered dichalcogenides anticipate the benefits of nanostructuration for more efficient optoelectronic devices. Notwithstanding great potential, this possibility remains still unexplored for MOFs. Overall, I seek to exploit MOFs' unparalleled chemical/structural flexibility to produce advanced crystalline materials that combine hydrolytical stability and tunable performance to be used in environmentally relevant applications like visible light photocatalysis. This is an emerging research front that holds great potential for influencing future R&D in Chemistry and Materials Science.
Metal-Organic-Frameworks (MOFs) offer appealing advantages over classical solids from combination of high surface areas with the crystallinity of inorganic materials and the synthetic versatility (unlimited combination of metals and linkers for fine tuning of properties) and processability of organic materials. Provided chemical stability, I expect combination of porosity with manipulable electrical and optical properties to open a new world of possibilities, with MOFs playing an emerging role in fields of key environmental value like photovoltaics, photocatalysis or electrocatalysis. The conventional insulating character of MOFs and their poor chemical stability (only a minimum fraction are hydrolytically stable) are arguably the two key limitations hindering further development in this context. With chem-fs-MOF I expect to deliver: 1. New synthetic routes specifically designed for producing new, hydrolytically stable Fe(III) and Ti(IV)-MOFs (new synthetic platforms for new materials). 2. More advanced crystalline materials to feature tunable function by chemical manipulation of MOF's optical/electrical properties and pore activity (function-led chemical engineering). 3. High-quality ultrathin films, reliant on the transfer of single-layers, alongside establishing the techniques required for evaluating their electric properties (key to device integration). Recent works on graphene and layered dichalcogenides anticipate the benefits of nanostructuration for more efficient optoelectronic devices. Notwithstanding great potential, this possibility remains still unexplored for MOFs. Overall, I seek to exploit MOFs' unparalleled chemical/structural flexibility to produce advanced crystalline materials that combine hydrolytical stability and tunable performance to be used in environmentally relevant applications like visible light photocatalysis. This is an emerging research front that holds great potential for influencing future R&D in Chemistry and Materials Science.
Project acronym CHEMBIOLPBINT
Project Chemical biology of natural products in plant-bacteria interactions
Researcher (PI) Markus Kaiser
Host Institution (HI) UNIVERSITAET DUISBURG-ESSEN
Summary This project deals with the elucidation of the biological role of natural products in plant-bacteria interactions. Plant-associated bacteria synthesize a vast number of biologically active natural products that modulate the physiology and functioning of their host plants. For example, plant pathogens often cause devastating crop losses by secreting low molecular weight phytotoxins, while some symbiotic bacteria biosynthesize plant-protecting compounds that assist in lowering biotic and abiotic plant stresses. It is therefore surprising that although natural products seem to play key roles in the complex interaction network between bacteria and plants, most of their biological functions and molecular targets are still unknown. To date, almost all studies on plant-bacteria interactions have been performed with biological approaches. Here, we propose to investigate the biological role of plant-associated natural products with the aid of a chemistry-driven approach, relying on the power of chemical synthesis to i) generate these natural products and/or suitable natural product derivatives, ii) to elucidate their targets in plants, and iii) to apply them in plant-bacteria studies. Although natural products have long been in the focus of chemical research, such a systematic chemistry-driven approach has, to our knowledge, never been performed before in plant-bacteria interactions. Our project will therefore not only serve to i) decipher basic research questions and ii) identify potential lead structures for agricultural and medicinal applications, but will also contribute to iii) the refinement of chemical syntheses strategies, iv) the advancement of target finding approaches and v) the establishment of chemical biology approaches in plant biology.
This project deals with the elucidation of the biological role of natural products in plant-bacteria interactions. Plant-associated bacteria synthesize a vast number of biologically active natural products that modulate the physiology and functioning of their host plants. For example, plant pathogens often cause devastating crop losses by secreting low molecular weight phytotoxins, while some symbiotic bacteria biosynthesize plant-protecting compounds that assist in lowering biotic and abiotic plant stresses. It is therefore surprising that although natural products seem to play key roles in the complex interaction network between bacteria and plants, most of their biological functions and molecular targets are still unknown. To date, almost all studies on plant-bacteria interactions have been performed with biological approaches. Here, we propose to investigate the biological role of plant-associated natural products with the aid of a chemistry-driven approach, relying on the power of chemical synthesis to i) generate these natural products and/or suitable natural product derivatives, ii) to elucidate their targets in plants, and iii) to apply them in plant-bacteria studies. Although natural products have long been in the focus of chemical research, such a systematic chemistry-driven approach has, to our knowledge, never been performed before in plant-bacteria interactions. Our project will therefore not only serve to i) decipher basic research questions and ii) identify potential lead structures for agricultural and medicinal applications, but will also contribute to iii) the refinement of chemical syntheses strategies, iv) the advancement of target finding approaches and v) the establishment of chemical biology approaches in plant biology.
Project acronym CHEMCOMP
Project Building-up Chemical Complexity into Multifunctional Molecule-based Hybrid Materials
Researcher (PI) Jose Ramon Galan Mascaros
Summary Molecular sciences offer unparalleled opportunities for the development of tailor-made materials. By chemical design, molecules with the desired features can be prepared and incorporated into hybrid systems to yield molecule-based materials with novel chemical and/or physical properties. The CHEMCOMP project aims to develop new hybrid materials targeting the study of new physical phenomena that have already been theoretically predicted or experimentally hinted. The main goals will be: i) Molecules with memory: Memory effect at the molecular scale is of great interest because it represents the size limit in the miniaturization of information storage media. My goal will be to develop spin crossover molecules with bulk-like hysteretic behavior where the switching between the low spin ground state and the high spin metastable state can be controlled through external stimuli. ii) Bistable organic conductors: Bistable molecules could also be embedded into hybrid organic conductors to induce structural phase transitions. This strategy will allow for the transport properties to be controlled through external stimuli in unprecedented switchable conducting media. iii) Hybrid conducting magnets: Combination of magnetism and electrical conductivity has given rise to new phenomena in the past, such as spin glass behavior or giant magnetoresistance. We propose to incorporate Single Molecule Magnets (molecules with magnet-like behavior) into organic (super)conductors to understand and optimize the synergy between these two physical properties. iv) Chiral magnets and conductors: New phenomena is expected to appear in optically active media. Experimental evidence for the so-called MagnetoChiral Dichroism has already been found. Electrical Magnetochiral Anisotropy has been predicted. I will develop systematic strategies for the preparation of hybrid chiral materials to understand and optimize the synergy between chirality and bulk physical properties.
Molecular sciences offer unparalleled opportunities for the development of tailor-made materials. By chemical design, molecules with the desired features can be prepared and incorporated into hybrid systems to yield molecule-based materials with novel chemical and/or physical properties. The CHEMCOMP project aims to develop new hybrid materials targeting the study of new physical phenomena that have already been theoretically predicted or experimentally hinted. The main goals will be: i) Molecules with memory: Memory effect at the molecular scale is of great interest because it represents the size limit in the miniaturization of information storage media. My goal will be to develop spin crossover molecules with bulk-like hysteretic behavior where the switching between the low spin ground state and the high spin metastable state can be controlled through external stimuli. ii) Bistable organic conductors: Bistable molecules could also be embedded into hybrid organic conductors to induce structural phase transitions. This strategy will allow for the transport properties to be controlled through external stimuli in unprecedented switchable conducting media. iii) Hybrid conducting magnets: Combination of magnetism and electrical conductivity has given rise to new phenomena in the past, such as spin glass behavior or giant magnetoresistance. We propose to incorporate Single Molecule Magnets (molecules with magnet-like behavior) into organic (super)conductors to understand and optimize the synergy between these two physical properties. iv) Chiral magnets and conductors: New phenomena is expected to appear in optically active media. Experimental evidence for the so-called MagnetoChiral Dichroism has already been found. Electrical Magnetochiral Anisotropy has been predicted. I will develop systematic strategies for the preparation of hybrid chiral materials to understand and optimize the synergy between chirality and bulk physical properties.
Project acronym CHEMMINE
Project Chemical proteome mining for functional annotation of disease relevant proteins
Researcher (PI) Stephan SIEBER
Summary Genome sequencing projects have provided unique insights into the cellular inventory of genes and their corresponding protein products. Despite this success, a large fraction of cellular proteins remains functionally uncharacterized. Their annotation represents a major challenge for contemporary research, reaching beyond the power of bioinformatic sequence similarity searches. Thus multidisciplinary strategies consolidating chemical and biological methods are required to close this gap. We here approach the challenge by two chemical proteomic platforms that focus on disease relevant sub-fractions of the uncharacterized proteome. The first platform utilizes functionalized cofactors that exploit cognate cellular uptake systems and report specific binding of large enzyme families. The molecules will be applied to mine cellular proteomes for unknown family members with crucial roles in diseases and assign their function. The second platform exploits phosphoaspartate as an important disease-related post-translational modification. Due to low stability, this transient modification currently escapes detection by established proteomic procedures. Moreover, little is known about the enzymes that catalyze aspartate phosphorylation. We here use specific nucleophilic traps that convert phosphoaspartate into stable modifications suitable for analytic detection. In addition, the complement of currently unknown phosphodonor proteins will be identified with customized tools. With these platforms we aim to functionally annotate sub-fractions of the uncharacterized proteome and utilize our tools for the identification of new drug targets by comparative analysis of healthy and diseased cells. Finally, we apply the camouflaged molecular design strategy in the synthesis of compound libraries to screen for candidate inhibitors against selected, disease-modulating targets. The previous record of my group in chemical proteomics provides a strong basis to achieve these challenging goals.
Genome sequencing projects have provided unique insights into the cellular inventory of genes and their corresponding protein products. Despite this success, a large fraction of cellular proteins remains functionally uncharacterized. Their annotation represents a major challenge for contemporary research, reaching beyond the power of bioinformatic sequence similarity searches. Thus multidisciplinary strategies consolidating chemical and biological methods are required to close this gap. We here approach the challenge by two chemical proteomic platforms that focus on disease relevant sub-fractions of the uncharacterized proteome. The first platform utilizes functionalized cofactors that exploit cognate cellular uptake systems and report specific binding of large enzyme families. The molecules will be applied to mine cellular proteomes for unknown family members with crucial roles in diseases and assign their function. The second platform exploits phosphoaspartate as an important disease-related post-translational modification. Due to low stability, this transient modification currently escapes detection by established proteomic procedures. Moreover, little is known about the enzymes that catalyze aspartate phosphorylation. We here use specific nucleophilic traps that convert phosphoaspartate into stable modifications suitable for analytic detection. In addition, the complement of currently unknown phosphodonor proteins will be identified with customized tools. With these platforms we aim to functionally annotate sub-fractions of the uncharacterized proteome and utilize our tools for the identification of new drug targets by comparative analysis of healthy and diseased cells. Finally, we apply the camouflaged molecular design strategy in the synthesis of compound libraries to screen for candidate inhibitors against selected, disease-modulating targets. The previous record of my group in chemical proteomics provides a strong basis to achieve these challenging goals.
Project acronym CHIRALLCARBON
Project Chiral Allotropes of Carbon
Researcher (PI) Nazario Martín
Host Institution (HI) UNIVERSIDAD COMPLUTENSE DE MADRID
Summary The aim of the present project is to answer fundamental questions about how to introduce chirality into a variety of carbon nanostructures and how it modifies the properties in the search for new applications in materials science and nanotecnology. Thus, it describes a fundamental and technological research program designed to gain new knowledge for the development of novel covalent and supramolecular chiral carbon nanoforms, and their further chemical modification for the preparation of sophisticated supramolecular 3D nanoarchitectures. Our research activity should reinforce and integrate the strong position of Europe in the knowledge of carbon nanoforms. This important scientific challenge has not been properly addressed so far due to the inherent difficulties to work on these materials and, particularly, to the lack of an efficient chemical protocol to prepare chiral carbon nanoforms.
The aim of the present project is to answer fundamental questions about how to introduce chirality into a variety of carbon nanostructures and how it modifies the properties in the search for new applications in materials science and nanotecnology. Thus, it describes a fundamental and technological research program designed to gain new knowledge for the development of novel covalent and supramolecular chiral carbon nanoforms, and their further chemical modification for the preparation of sophisticated supramolecular 3D nanoarchitectures. Our research activity should reinforce and integrate the strong position of Europe in the knowledge of carbon nanoforms. This important scientific challenge has not been properly addressed so far due to the inherent difficulties to work on these materials and, particularly, to the lack of an efficient chemical protocol to prepare chiral carbon nanoforms.
Project acronym CHMIFLUORS
Project Carbohydrate Mimesis using Fluorinated Sugars for Chemical Biology: From Reaction Design to Applications in Molecular Imaging
Researcher (PI) Ryan Gilmour
Summary The principle objective of this proposal is to validate fluorinated glyco-structures as effective carbohydrate mimics for the next frontier in pharmaceutical research. Herein we propose to capitalise on the major advances in statistical data analysis which are unravelling the complexity of mammalian and bacterial "glycospace". Molecular mimicry is a powerful drug design approach. It is therefore envisaged to develop a focussed programme of research to validate fluorinated glycostructures, and in particular 2-fluoro sugars, as carbohydrate mimics for chemical biology, exploiting the ubiquitous role of carbohydrates in molecular recognition. Salient features of the 2-fluoro substituent include (i) enhanced hydrolytic stability to enzymatic degradation, (ii) the presence of a NMR active reporter nucleus (19F) for facile analysis, and (iii) the possibility for molecular imaging application when using 18F labelled glycostructures. Phase one of this project will aim to develop synthetic routes to the target fluoro-glycostructures. This will involve a substantial component of physical organic chemistry including conformational analysis, advanced 19F NMR spectroscopy and the possible isolation of oxo-carbenium analogues by exploiting advances in the development of large, weakly co-ordinating anions. From first principle reaction design and development, through a basic understanding of conformation and reactivity, phase 2 will focus on the application of these materials for chemical biology applications. Phase 2 will then heavily focus on the application of complex oligosaccharides containing the PET active 18F moiety. It is envisaged that by exploiting the ubiquitous role of carbohydrates in molecular recognition that this would conceivably lead to the development of selective imaging agents, thus bypassing the current problem of relying on the metabolically controlled distribution of the commonly used PET tracer 2-fluorodeoxy glucose (18F-FDG).
The principle objective of this proposal is to validate fluorinated glyco-structures as effective carbohydrate mimics for the next frontier in pharmaceutical research. Herein we propose to capitalise on the major advances in statistical data analysis which are unravelling the complexity of mammalian and bacterial "glycospace". Molecular mimicry is a powerful drug design approach. It is therefore envisaged to develop a focussed programme of research to validate fluorinated glycostructures, and in particular 2-fluoro sugars, as carbohydrate mimics for chemical biology, exploiting the ubiquitous role of carbohydrates in molecular recognition. Salient features of the 2-fluoro substituent include (i) enhanced hydrolytic stability to enzymatic degradation, (ii) the presence of a NMR active reporter nucleus (19F) for facile analysis, and (iii) the possibility for molecular imaging application when using 18F labelled glycostructures. Phase one of this project will aim to develop synthetic routes to the target fluoro-glycostructures. This will involve a substantial component of physical organic chemistry including conformational analysis, advanced 19F NMR spectroscopy and the possible isolation of oxo-carbenium analogues by exploiting advances in the development of large, weakly co-ordinating anions. From first principle reaction design and development, through a basic understanding of conformation and reactivity, phase 2 will focus on the application of these materials for chemical biology applications. Phase 2 will then heavily focus on the application of complex oligosaccharides containing the PET active 18F moiety. It is envisaged that by exploiting the ubiquitous role of carbohydrates in molecular recognition that this would conceivably lead to the development of selective imaging agents, thus bypassing the current problem of relying on the metabolically controlled distribution of the commonly used PET tracer 2-fluorodeoxy glucose (18F-FDG).
Project acronym CMetC
Project Selective Carbon-Carbon Bond Activation: A Wellspring of Untapped Reactivity
Summary The creation of new molecular entities and subsequent exploitation of their properties is central to a broad spectrum of research disciplines from medicine to materials. Most –if not all- of the efforts of organic chemists were directed to the development of creative strategies to built carbon-carbon and carbon-heteroatom bonds in a predictable and efficient manner. But is the creation of new bonds the only approach that organic chemistry should follow? Could we design the synthesis of challenging molecular skeleton no more through the construction of carbon-carbon bonds but rather through selective cleavage of carbon-carbon bonds (C-C bond activation)? The goal of this work is to develop powerful synthetic approaches for the selective C-C bond activation and demonstrate that it has the potential to be a general principle in organic synthesis for the regio-, diastereo- and even enantiomerically enriched preparation of adducts despite that C-C single bonds belong among the least reactive functional groups in chemistry. The realization of this synthetic potential requires the ability to functionalize selectively one C-C bond in compounds containing many such bonds and an array of functional groups. This site selective C-C bond activation is one of the greatest challenges that must be met to be used widely in complex-molecular synthesis. To emphasize the practicality of C-C bond activation, we will prepare in a single-pot operation challenging molecular framework possessing various stereogenic centers from very simple starting materials through selective C-C bond activation. Ideally, alkenes will be in-situ transformed into alkanes that will subsequently undergo the C-C activation even in the presence of functional group. This work will lead to ground-breaking advances when non-strained cycloalkanes (cyclopentane, cyclohexane) will undergo this smooth C-C bond activation with friendly and non toxic organometallic species.
The creation of new molecular entities and subsequent exploitation of their properties is central to a broad spectrum of research disciplines from medicine to materials. Most –if not all- of the efforts of organic chemists were directed to the development of creative strategies to built carbon-carbon and carbon-heteroatom bonds in a predictable and efficient manner. But is the creation of new bonds the only approach that organic chemistry should follow? Could we design the synthesis of challenging molecular skeleton no more through the construction of carbon-carbon bonds but rather through selective cleavage of carbon-carbon bonds (C-C bond activation)? The goal of this work is to develop powerful synthetic approaches for the selective C-C bond activation and demonstrate that it has the potential to be a general principle in organic synthesis for the regio-, diastereo- and even enantiomerically enriched preparation of adducts despite that C-C single bonds belong among the least reactive functional groups in chemistry. The realization of this synthetic potential requires the ability to functionalize selectively one C-C bond in compounds containing many such bonds and an array of functional groups. This site selective C-C bond activation is one of the greatest challenges that must be met to be used widely in complex-molecular synthesis. To emphasize the practicality of C-C bond activation, we will prepare in a single-pot operation challenging molecular framework possessing various stereogenic centers from very simple starting materials through selective C-C bond activation. Ideally, alkenes will be in-situ transformed into alkanes that will subsequently undergo the C-C activation even in the presence of functional group. This work will lead to ground-breaking advances when non-strained cycloalkanes (cyclopentane, cyclohexane) will undergo this smooth C-C bond activation with friendly and non toxic organometallic species.
Project acronym COFLeaf
Project Fuel from sunlight: Covalent organic frameworks as integrated platforms for photocatalytic water splitting and CO2 reduction
Researcher (PI) Bettina Valeska Lotsch
Summary The efficient conversion of solar energy into renewable chemical fuels has been identified as one of the grand challenges facing society today and one of the major driving forces of materials innovation. Nature's photosynthesis producing chemical fuels through the revaluation of sunlight has inspired generations of chemists to develop platforms mimicking the natural photosynthetic process, albeit at lower levels of complexity. While artificial photosynthesis remains a considerable challenge due to the intricate interplay between materials design, photochemistry and catalysis, the spotlights – light-driven water splitting into hydrogen and oxygen and carbon dioxide reduction into methane or methanol – have emerged as viable pathways into both a clean and sustainable energy future. With this proposal, we aim at introducing a new class of polymeric photocatalysts based on covalent organic frameworks, COFs, to bridge the gap between semiconductor and molecular systems and explore rational ways to design single-site heterogeneous photocatalysts offering both chemical tunability and stability. The development of a photocatalytic model system is proposed, which will be tailored by molecular synthetic protocols and optimized by solid-state chemical procedures and crystal engineering so as to provide insights into the architectures, reactive intermediates and mechanistic steps involved in the photocatalytic process, with complementary insights from theory. We envision the integration of various molecular subsystems including photosensitizers, redox shuttles and molecular co-catalysts in a single semiconducting COF backbone. Taking advantage of the hallmarks of COFs – molecular definition and tunability, crystallinity, porosity and rigidity – we describe the design of COF systems capable of light-induced hydrogen evolution, oxygen evolution and overall water splitting, and delineate strategies to use COFs as integrated platforms for CO2 capture, activation and conversion.
The efficient conversion of solar energy into renewable chemical fuels has been identified as one of the grand challenges facing society today and one of the major driving forces of materials innovation. Nature's photosynthesis producing chemical fuels through the revaluation of sunlight has inspired generations of chemists to develop platforms mimicking the natural photosynthetic process, albeit at lower levels of complexity. While artificial photosynthesis remains a considerable challenge due to the intricate interplay between materials design, photochemistry and catalysis, the spotlights – light-driven water splitting into hydrogen and oxygen and carbon dioxide reduction into methane or methanol – have emerged as viable pathways into both a clean and sustainable energy future. With this proposal, we aim at introducing a new class of polymeric photocatalysts based on covalent organic frameworks, COFs, to bridge the gap between semiconductor and molecular systems and explore rational ways to design single-site heterogeneous photocatalysts offering both chemical tunability and stability. The development of a photocatalytic model system is proposed, which will be tailored by molecular synthetic protocols and optimized by solid-state chemical procedures and crystal engineering so as to provide insights into the architectures, reactive intermediates and mechanistic steps involved in the photocatalytic process, with complementary insights from theory. We envision the integration of various molecular subsystems including photosensitizers, redox shuttles and molecular co-catalysts in a single semiconducting COF backbone. Taking advantage of the hallmarks of COFs – molecular definition and tunability, crystallinity, porosity and rigidity – we describe the design of COF systems capable of light-induced hydrogen evolution, oxygen evolution and overall water splitting, and delineate strategies to use COFs as integrated platforms for CO2 capture, activation and conversion.
Project acronym COINFLIP
Project Coupled Organic Inorganic Nanostructures for Fast, Light-Induced Data Processing
Researcher (PI) Marcus Scheele
Host Institution (HI) EBERHARD KARLS UNIVERSITAET TUEBINGEN
Summary The main objective of this project is to design optical switches with a response time < 5 ps, a switching energy < 1 fJ/bit and compatibility with silicon technology to excel in high-speed data processing at low heat dissipation. This will be pursued by combining the chemistry of inorganic, nanocrystalline colloids and organic semiconductor molecules to fabricate thin films of organic-inorganic hybrid nanostructures. Optical switches play a pivotal role in modern data processing based on silicon photonics, where they control the interface between photonic optical fibers used for data transmission and electronic processing units for computing. Data transfer across this interface is slow compared to that in optical interconnects and high-speed silicon transistors, such that faster optical switching accelerates the overall speed of data processing of the system as a whole. By modifying the surface of the inorganic nanocrystals with conductive molecular linkers and self-assembly into macroscopic solid state materials, new electronic and photonic properties arise due to charge transfer at the organic/inorganic interface. The multiple optical resonances in these hybrid materials result in strong optoelectronic interactions with external light beams, which are exploited for converting photonic into electronic signals at unprecedented speed. A key concept here is an activated absorption mechanism, in which the nanocrystals act as sensitizers with short-lived excited states, which are activated by a first optical pump beam. Efficient charge transfer at the organic/inorganic interface temporarily creates additional resonances in the molecular linkers, which may be probed by a second optical beam for as long as the sensitizer is in its excited state. Utilizing nanocrystals with excited state lifetimes < 5ps will reward ultrafast response times to pave the way for novel optical switches and high-speed data processing rates for silicon photonics.
The main objective of this project is to design optical switches with a response time < 5 ps, a switching energy < 1 fJ/bit and compatibility with silicon technology to excel in high-speed data processing at low heat dissipation. This will be pursued by combining the chemistry of inorganic, nanocrystalline colloids and organic semiconductor molecules to fabricate thin films of organic-inorganic hybrid nanostructures. Optical switches play a pivotal role in modern data processing based on silicon photonics, where they control the interface between photonic optical fibers used for data transmission and electronic processing units for computing. Data transfer across this interface is slow compared to that in optical interconnects and high-speed silicon transistors, such that faster optical switching accelerates the overall speed of data processing of the system as a whole. By modifying the surface of the inorganic nanocrystals with conductive molecular linkers and self-assembly into macroscopic solid state materials, new electronic and photonic properties arise due to charge transfer at the organic/inorganic interface. The multiple optical resonances in these hybrid materials result in strong optoelectronic interactions with external light beams, which are exploited for converting photonic into electronic signals at unprecedented speed. A key concept here is an activated absorption mechanism, in which the nanocrystals act as sensitizers with short-lived excited states, which are activated by a first optical pump beam. Efficient charge transfer at the organic/inorganic interface temporarily creates additional resonances in the molecular linkers, which may be probed by a second optical beam for as long as the sensitizer is in its excited state. Utilizing nanocrystals with excited state lifetimes < 5ps will reward ultrafast response times to pave the way for novel optical switches and high-speed data processing rates for silicon photonics.
Project acronym COMBAT
Project Computational Modeling and Design of Lithium-Ion Batteries
Researcher (PI) Timon Rabczuk
Host Institution (HI) BAUHAUS-UNIVERSITAET WEIMAR
Summary "Lithium-ion batteries (LIBs) are among the most promising solutions for energy storage. Compared with other resources such as bio-fuel, solar cells, fuel cells or lead acid batteries, rechargeable batteries are more portable and allow for quick energy storage and release. The higher power and energy density make batteries suitable as the energy resource for most portable elect. devices including future vehicles. Among the rechargeable batteries, LIBs have the most potential because of their quick charging rate and high power and energy density. However, ageing of LIBs and the related capacity and power fade is a major concern. For the improvement and future development of batteries, computational modeling and design is an important complementary part to experimental testing which is expensive, time-consuming and sometimes unfeasible. In this project, the PI proposes to develop, implement, verify and validate a computational multifield and multiscale framework to support the design and optimization of new batteries. The computational framework will support the design and optimization of new anode, separator and cathode materials as well as their structure inside the battery. The measurable outcome of this research will be an open-source software package that can be used to support the design and optimization of LIBs. Within the computational framework, different (mechanical-thermal-electro-chemical) fields will be linked over multiple scales: from fundamental physics to the design of new battery materials. We will quantify uncertainties in order to provide upper and lower bounds of our predictions and use graph-theory, error-estimation and adaptivity to choose the appropriate model and discretization. The computational framework will be verified and validated by comparison to experiments. Finally, multi-objective optimization over multiple scales will provide a new battery prototype that will be manufactured, tested and compared to the computational predictions."
"Lithium-ion batteries (LIBs) are among the most promising solutions for energy storage. Compared with other resources such as bio-fuel, solar cells, fuel cells or lead acid batteries, rechargeable batteries are more portable and allow for quick energy storage and release. The higher power and energy density make batteries suitable as the energy resource for most portable elect. devices including future vehicles. Among the rechargeable batteries, LIBs have the most potential because of their quick charging rate and high power and energy density. However, ageing of LIBs and the related capacity and power fade is a major concern. For the improvement and future development of batteries, computational modeling and design is an important complementary part to experimental testing which is expensive, time-consuming and sometimes unfeasible. In this project, the PI proposes to develop, implement, verify and validate a computational multifield and multiscale framework to support the design and optimization of new batteries. The computational framework will support the design and optimization of new anode, separator and cathode materials as well as their structure inside the battery. The measurable outcome of this research will be an open-source software package that can be used to support the design and optimization of LIBs. Within the computational framework, different (mechanical-thermal-electro-chemical) fields will be linked over multiple scales: from fundamental physics to the design of new battery materials. We will quantify uncertainties in order to provide upper and lower bounds of our predictions and use graph-theory, error-estimation and adaptivity to choose the appropriate model and discretization. The computational framework will be verified and validated by comparison to experiments. Finally, multi-objective optimization over multiple scales will provide a new battery prototype that will be manufactured, tested and compared to the computational predictions."
Project acronym COMBIPATTERNING
Project Combinatorial Patterning of Particles for High Density Peptide Arrays
Researcher (PI) Alexander Nesterov-Mueller
Host Institution (HI) KARLSRUHER INSTITUT FUER TECHNOLOGIE
Summary We want to use selective laser melting to pattern a substrate with different solid micro particles at a density of 1 million spots per cm2. First, a homogeneous particle layer is deposited on a substrate and a pattern of micro spots of melted matrix is generated by laser radiation. Then, non-melted particles are blown away. Embedded within the particles are different chemically reactive amino acid derivatives that will start coupling to very small synthesis sites upon melting the particle pattern in an oven. This is done once all of the 20 different amino acid particles have been glued by laser patterning to the surface. Washing away uncoupled material, removing Fmoc protecting group, and repeating the patterning steps according to standard Merrifield synthesis, leads to the combinatorial synthesis of very high-density peptide arrays. The main objective of this proposal is to develop this method up to the level of a semi-automated synthesis machine. In addition, we will use the manufactured very high-density peptide arrays to readout the information that is deposited in the immune system, i.e. find a peptide binder for every one of the 200-500 antibody species that patrol the serum of an individual in elevated levels. These experiments might lead to novel tools to find out the causes of hitherto enigmatic diseases because then we might be able to correlate antibody patterns with disease status without knowing in advance the disease-specific antibodies. Beyond the life sciences, we want to embed 10.000 peptides per cm2 within an insulating layer of alkane thiols, each on a different gold pad of a specially designed screening chip. Then, we could readout I/V characteristics of individual peptide species, and eventually find peptide-based diodes. These could be modified in their sequence and screened again for better performance. This evolution-inspired screening approach might lead to novel materials that could be used in fuel cells.
We want to use selective laser melting to pattern a substrate with different solid micro particles at a density of 1 million spots per cm2. First, a homogeneous particle layer is deposited on a substrate and a pattern of micro spots of melted matrix is generated by laser radiation. Then, non-melted particles are blown away. Embedded within the particles are different chemically reactive amino acid derivatives that will start coupling to very small synthesis sites upon melting the particle pattern in an oven. This is done once all of the 20 different amino acid particles have been glued by laser patterning to the surface. Washing away uncoupled material, removing Fmoc protecting group, and repeating the patterning steps according to standard Merrifield synthesis, leads to the combinatorial synthesis of very high-density peptide arrays. The main objective of this proposal is to develop this method up to the level of a semi-automated synthesis machine. In addition, we will use the manufactured very high-density peptide arrays to readout the information that is deposited in the immune system, i.e. find a peptide binder for every one of the 200-500 antibody species that patrol the serum of an individual in elevated levels. These experiments might lead to novel tools to find out the causes of hitherto enigmatic diseases because then we might be able to correlate antibody patterns with disease status without knowing in advance the disease-specific antibodies. Beyond the life sciences, we want to embed 10.000 peptides per cm2 within an insulating layer of alkane thiols, each on a different gold pad of a specially designed screening chip. Then, we could readout I/V characteristics of individual peptide species, and eventually find peptide-based diodes. These could be modified in their sequence and screened again for better performance. This evolution-inspired screening approach might lead to novel materials that could be used in fuel cells.