ERC FUNDED PROJECTS

"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."

1 500 000 €

Start date: 2012-09-01, End date: 2017-08-31

The objective of this proposal is to determine the unknown criteria for convective cross-flow in bicontinuous interfacially jammed emulsion gels (bijels). Based on this, we will answer the question: Can continuously operated interfacial catalysis be realized in bijel cross-flow reactors? Demonstrating this potential will introduce a broadly applicable chemical technology, replacing wasteful chemical processes that require organic solvents. We will achieve our objective in three steps: (a) Control over bijel structure and properties. Bijels will be formed with a selection of functional inorganic colloidal particles. Nanoparticle surface modifications will be developed and extensively characterized. General principles for the parameters determining bijel structures and properties will be established based on confocal and electron microscopy characterization. These principles will enable unprecedented control over bijel formation and will allow for designing desired properties. (b) Convective flow in bijels. The mechanical strength of bijels will be tailored and measured. With mechanically robust bijels, the influence of size and organization of oil/water channels on convective mass transfer in bijels will be investigated. To this end, a bijel mass transfer apparatus fabricated by 3d-printing of bijel fibers and soft photolithography will be introduced. In conjunction with the following objective, the analysis of convective flows in bijels will facilitate a thorough description of their structure/function relationships. (c) Biphasic chemical reactions in STrIPS bijel cross-flow reactors. First, continuous extraction in bijels will be realized. Next, conditions to carry out continuously-operated, phase transfer catalysis of well-known model reactions in bijels will be determined. Both processes will be characterized in-situ and in 3-dimensions by confocal microscopy of fluorescent phase transfer reactions in transparent bijels.

1 905 000 €

Start date: 2019-06-01, End date: 2024-05-31

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.

2 410 771 €

Start date: 2018-10-01, End date: 2023-09-30

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.

1 499 219 €

Start date: 2017-03-01, End date: 2022-02-28

"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."

2 194 000 €

Start date: 2014-02-01, End date: 2019-01-31

Two-dimensional transition metal dichalcogenides (2D-TMDs) are an exciting class of new materials. Their ultrathin body, optical band gap and unusual spin and valley polarization physics make them very promising candidates for a vast new range of (opto-)electronic applications. So far, most experimental work on 2D-TMDs has been performed on exfoliated flakes made by the ‘Scotch tape’ technique. The major next challenge is the large-area synthesis of 2D-TMDs by a technique that ultimately can be used for commercial device fabrication. Building upon pure 2D-TMDs, even more functionalities can be gained from 2D-TMD alloys and heterostructures. Theoretical work on these derivates reveals exciting new phenomena, but experimentally this field is largely unexplored due to synthesis technique limitations. The goal of this proposal is to combine atomic layer deposition with plasma chemistry to create a novel surface-controlled, industry-compatible synthesis technique that will make large area 2D-TMDs, 2D-TMD alloys and 2D-TMD heterostructures a reality. This innovative approach will enable systematic layer dependent studies, likely revealing exciting new properties, and provide integration pathways for a multitude of applications. Atomistic simulations will guide the process development and, together with in- and ex-situ analysis, increase the understanding of the surface chemistry involved. State-of-the-art high resolution transmission electron microscopy will be used to study the alloying process and the formation of heterostructures. Luminescence spectroscopy and electrical characterization will reveal the potential of the synthesized materials for (opto)-electronic applications. The synergy between the excellent background of the PI in 2D materials for nanoelectronics and the group’s leading expertise in ALD and plasma science is unique and provides an ideal stepping stone to develop the synthesis of large-area 2D-TMDs and derivatives.

1 968 709 €

Start date: 2015-08-01, End date: 2020-07-31

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.

1 452 000 €

Start date: 2010-12-01, End date: 2016-05-31

"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. "

1 497 000 €

Start date: 2016-04-01, End date: 2021-03-31

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.

1 500 000 €

Start date: 2010-11-01, End date: 2015-10-31

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.

2 427 000 €

Start date: 2014-03-01, End date: 2019-02-28

Living organisms have acquired new functionalities by uptake and integration of species to create symbiotic life-forms. This process of endosymbiosis has intrigued scientists over the years, albeit mostly from an evolution biology perspective. With the advance of chemical and synthetic biology, our ability to create molecular-life-like systems has increased tremendously, which enables us to build cell and organelle-like structures. However, these advances have not been taken to a level to study comprehensively if endosymbiosis can be applied to non-living systems or to integrate living with non-living matter. The aim of the research described in the ARTISYM proposal is to establish the field of artificial endosymbiosis. Two lines of research will be followed. First, we will incorporate artificial organelles in living cells to design hybrid cells with acquired functionality. This investigation is scientifically of great interest, as it will show us how to introduce novel compartmentalized pathways into living organisms. It also serves an important societal goal, as with these compartments dysfunctional cellular processes can be corrected. We will follow both a transient and a permanent approach. With the transient route biodegradable nanoreactors are introduced to supply living cells temporarily with novel function. Functionality is permanently introduced using genetic engineering to express protein-based nanoreactors in living cells, or via organelle transplantation of healthy mitochondria in diseased living cells. Secondly I aim to create artificial cells with the ability to perform endosymbiosis; the uptake and presence of artificial organelles in synthetic vesicles allows them to dynamically respond to their environment. Responses that are envisaged are shape changes, motility, and growth and division. Furthermore, the incorporation of natural organelles in liposomes provides biocatalytic cascades with the necessary cofactors to function in an artificial cell

2 500 000 €

Start date: 2017-01-01, End date: 2021-12-31

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.

3 473 400 €

Start date: 2011-04-01, End date: 2017-03-31

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.

2 491 250 €

Start date: 2017-08-01, End date: 2022-07-31

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.

1 920 697 €

Start date: 2017-06-01, End date: 2022-05-31

Meta-materials, best known for their extraordinary properties (e.g. negative stiffness), are halfway from both materials and structures: their unusual properties are direct results of their complex 3D structures. This project introduces a new class of meta-materials called meta-biomaterials. Meta-biomaterials go beyond meta-materials by adding an extra dimension to the complex 3D structure, i.e. complex and precisely controlled surface nano-patterns. The 3D structure gives rise to unprecedented or rare combination of mechanical (e.g. stiffness), mass transport (e.g. permeability, diffusivity), and biological (e.g. tissue regeneration rate) properties. Those properties optimize the distribution of mechanical loads and the transport of nutrients and oxygen while providing geometrical shapes preferable for tissue regeneration (e.g. higher curvatures). Surface nano-patterns communicate with (stem) cells, control their differentiation behavior, and enhance tissue regeneration. There is one important problem: meta-biomaterials cannot be manufactured with current technology. 3D printing can create complex shapes while nanolithography creates complex surface nano-patterns down to a few nanometers but only on flat surfaces. There is, however, no way of combining complex shapes with complex surface nano-patterns. The groundbreaking nature of this project is in solving that deadlock using the Origami concept (the ancient Japanese art of paper folding). In this approach, I first decorate flat 3D-printed sheets with nano-patterns. Then, I apply Origami techniques to fold the decorated flat sheet and create complex 3D shapes. The sheet knows how to self-fold to the desired structure when subjected to compression, owing to pre-designed joints, crease patterns, and thickness/material distributions that control its mechanical instability. I will demonstrate the added value of meta-biomaterials in improving bone tissue regeneration using in vitro cell culture assays and animal models

1 499 600 €

Start date: 2016-02-01, End date: 2021-01-31

From a polymer chemistry perspective, the way in which nature produces its plethora of different proteins is a miracle of precision: the synthesis of each single molecule is directed by the sequence information chemically coded in DNA. The present state of recombinant DNA technology should in principle allow us to make genes that code for entirely new, very sophisticated amino acid polymers, which are chosen and designed by man to serve as new polymer materials. It has been shown that it is indeed possible to make use of the protein biosynthetic machinery and produce such de novo protein polymers, but it is not clear what their potentials are in terms of new materials with desired functionalities. I propose to develop a new class of protein polymers, chosen such that they form nanostructured materials by triggered folding and multimolecular assembly. The plan is based on three innovative ideas: (i) each new protein polymer will be constructed from a limited set of selected amino acid sequences, called modules (hence the term modular protein polymers) (ii) new, high-yield fermentation strategies will be developed so that polymers will become available in significant quantities for evaluation and application; (iii) the design of modular protein polymers is carried out as a cyclic process in which sequence selection, construction of artificial genes, optimisation of fermentation for high yield, studying polymer folding and assembly, and modelling of the nanostructure by molecular simulation are all logically connected, allowing efficient selection of target sequences. This project is a cross-road. It brings together biotechnology and polymer science, creating a unique set of biomaterials for medical and pharmaceutical use, that can be easily extended into a manifold of biofunctional materials. Moreover, it will provide us with fresh tools and valuable insights to tackle the subtle relations between protein sequence and folding.

2 497 044 €

Start date: 2011-05-01, End date: 2016-04-30

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

2 496 762 €

Start date: 2011-05-01, End date: 2016-04-30

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.

2 483 136 €

Start date: 2017-09-01, End date: 2022-08-31

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).

1 688 705 €

Start date: 2017-01-01, End date: 2021-12-31

Amines are crucially important classes of chemicals, widely present in pharmaceuticals, agrochemicals and surfactants. Yet, surprisingly, a systematic approach to obtaining this essential class of compounds from renewables has not been realized to date. The aim of this proposal is to enable chemical pathways for the production of amines through alcohols from renewable resources, preferably lignocellulose waste. Two key scientific challenges will be addressed: The development of efficient cleavage reactions of complex renewable resources by novel heterogeneous catalysts; and finding new homogeneous catalyst based on earth-abundant metals for the atom-economic coupling of the derived alcohol building blocks directly with ammonia as well as possible further functionalization reactions. The program is divided into 3 interrelated but not mutually dependent work packages, each research addressing a key challenge in their respective fields, these are: WP1: Lignin conversion to aromatics; WP2: Cellulose-derived platform chemicals to aromatic and aliphatic diols and solvents. WP3: New iron-based homogeneous catalysts for the direct, atom-economic C-O to C-N transformations. The approach taken will embrace the inherent complexity present in the renewable feedstock. A unique balance between cleavage and coupling pathways will allow to access chemical diversity in products that is necessary to achieve economic competitiveness with current fossil fuel-based pathways and will permit rapid conversion to higher value products such as functionalized amines that can enter the chemical supply chain at a much later stage than bulk chemicals derived from petroleum. The proposed high risk-high gain research will push the frontiers of sustainable and green chemistry and reach well beyond state of the art in this area. This universal, flexible and iterative approach is anticipated to give rise to a variety of similar systems targeting diverse product outcomes starting from renewables.

1 500 000 €

Start date: 2016-05-01, End date: 2021-04-30

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.

2 499 060 €

Start date: 2013-03-01, End date: 2018-02-28

Aging worldwide population demands new solutions to permanently restore damaged tissues, thus reducing healthcare costs. Regenerative medicine offers alternative therapies for tissue repair. Although first clinical trials revealed excellent initial response after implantation of these engineered tissues, long-term follow-ups demonstrated that degeneration and lack of integration with the surrounding tissues occur. Causes are related to insufficient cell-material interactions and loss of cell potency when cultured in two-dimensional substrates, among others. Stem cells are a promising alternative due to their differentiation potential into multiple lineages. Yet, better control over cell-material interactions is necessary to maintain tissue engineered constructs in time. It is crucial to control stem cell quiescence, proliferation and differentiation in three-dimensional scaffolds while maintaining cells viable in situ. Stem cell activity is controlled by a complex cascade of signals called “niche”, where the extra-cellular matrix (ECM) surrounding the cells play a major role. Designing scaffolds inspired by this cellular niche and its ECM may lead to engineered tissues with instructive properties characterized by enhanced homeostasis, stability and integration with the surrounding milieu. This research proposal aims at engineering constructs where scaffolds work as stem cell delivery systems actively controlling cell quiescence, proliferation, and differentiation. This challenge will be approached through a biomimetic design inspired by the mesenchymal stem cell niche. Three different scaffolds will be combined to achieve this purpose: (i) a scaffold designed to maintain cell quiescence; (ii) a scaffold designed to promote cell proliferation; and (iii) a scaffold designed to control cell differentiation. To prove the design criteria the evaluation of stem cell quiescence, proliferation, and differentiation will be assessed for musculoskeletal regenerative therapies.

1 500 000 €

Start date: 2015-05-01, End date: 2020-04-30

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.

1 527 351 €

Start date: 2017-01-01, End date: 2021-12-31

"Sphingolipids are major components of the human cell and are involved in human pathologies ranging from lysosomal storage disorders to type 2 diabetes. Here, we propose to establish an integrated research program for the study of sphingolipid metabolism, in health and disease. We will combine state-of-the-art synthetic organic chemistry, bioorganic chemistry, analytical chemistry, molecular biology and biochemistry techniques and concepts and apply these in an integrated chemical biology approach to study and manipulate sphingolipid metabolism in vivo and in vitro, using human cells and animal models. The program is subdivided in three individual research lines that are interconnected both in terms of technology development and in their biological context. 1) We will develop modified sphinganine derivatives and apply these to study sphingolipid homeostasis in cells derived from healthy and diseased (Gaucher, Fabry, Niemann-Pick A/B disease) individuals/animal models. This question will be addressed in a chemical metabolomics/lipidomics approach. 2) We will develop activity-based probes aimed at monitoring enzyme activity levels of glycosidases involved in (glyco)sphingolipid metabolism, in particular the enzymes that - when mutated and thereby reduced in activity- are responsible for the lysosomal storage disorders Gaucher disease and Fabry disease. 3) We will develop well-defined enzymes and chaperone proteins for directed correction of sphingolipid homeostasis in Gaucher, Fabry and Niemann-Pick A/B patients, via a newly designed semi-synthetic approach that combines sortase-mediated ligation with synthetic chemistry. Deliverables are a better understanding of the composition of the sphingolipid pool that are at the basis of lysosomal storage disorders, effective ways to in situ monitor the efficacy of therapies (enzyme inhibitors, chemical chaperones, recombinant enzymes) to treat these and improved semi-synthetic proteins for enzyme replacement therapy."

2 999 600 €

Start date: 2012-06-01, End date: 2017-05-31