ERC FUNDED PROJECTS

Primary energy conversion in nature is powered by highly efficient enzymes that capture chemical or light energy and transduce it into other energy forms. These processes are catalyzed by coupled transfers of protons and electrons (PCET), but their fundamental mechanistic principles are not well understood. In order to obtain a molecular-level understanding of the functional elements powering biological energy conversion processes, we will study the catalytic machinery of one of the largest and most intricate enzymes in mitochondria and bacteria, the respiratory complex I. This gigantic redox-driven proton-pump functions as the entry point for electrons into aerobic respiratory chains, and it employs the energy released from a chemical reduction process to transport protons up to 200 Å away from its active site. Its molecular structure from bacteria and eukaryotes was recently resolved, but the origin of this remarkable action-at-a-distance effect still remains unclear. We employ and develop multi-scale quantum and classical molecular simulation techniques in combination with de novo-protein design methodology to identify and isolate the functional elements that catalyze the long-range PCET reactions in complex I. To fully understand the natural PCET-elements, we will further engineer central parts of this machinery into artificial protein frameworks, with the goal of designing modules for redox-driven proton pumps from first principles. The project aims to establish a fundamental understanding of nature's toolbox of catalytic elements, to elucidate how the complex biochemical environment contributes to the catalytic effects, and to provide blueprints that can guide the design of man-made enzymes for sustainable energy technology.

1 494 368 €

Start date: 2017-02-01, End date: 2022-01-31

CHEMO-RISK aims for a novel scientifically sound chemical risk assessment paradigm that integrates exposure and effect assessment of a broad range of chemicals into a single procedure and provides information relevant to ecosystem and human health. The key innovation is polymer “chemometers” that will be equilibrated with their surroundings and deliver information on the pollutant’s chemical activity in the environment, biota, and humans. A chemometer functions analogously to a thermometer, but instead of the temperature, it yields a measure of chemical activity. Chemical activity in turn indicates the thermodynamic potential for, e.g., partitioning, biouptake and toxicity. CHEMO-RISK aims at breaking the current paradigm in environmental risk assessment of single chemicals that disregards bioavailability, ignores mixture effects, lacks site-specificity and is difficult to extrapolate to human health. The chemometer extracts will be investigated using top-notch (a) GC and LC/Orbitrap chemical analysis to characterise the pollutant mixtures and (b) cell-based reporter gene bioassays to determine mixture effects covering baseline toxicity, specific (e.g., endocrine disruption) and reactive (e.g., genotoxicity) modes of toxic action and adaptive stress responses. Within CHEMO-RISK, the following important research questions will be tackled: (A) Which processes drive the enrichment of pollutants in aquatic biota on a thermodynamic basis? (B) How do pollutants distribute within an organism, and which effects do they elicit at the key target sites? (C) Can we apply everyday-life items such as eyeglass-nose pads to replace invasive sampling in human health risk assessment? (D) To which degree can non-target analysis of chemometer extracts explain the observed toxicity profiles across media? By combining all these research efforts, CHEMO-RISK will provide a unified risk assessment paradigm with risk-based trigger values distinguishing acceptable from unacceptable effects.

1 496 030 €

Start date: 2017-05-01, End date: 2022-04-30

Novel and improved nanomaterials with luminescent properties shall be synthesized in ionic liquids (ILs). In this approach the advantages of ionic liquids in nanoparticles synthesis (high nucleation rate, excellent electrosteric nanoparticles (NP) stabilization, morphology control, tunable properties) shall be combined with two unconventional synthesis methods that again take advantage of unique IL properties to obtain unprecedented compounds. Using a completely new and unconventional approach by evaporating metals, intermetallic phases or metal oxides and fluorides under high vacuum (negligible vapour pressure, low flammabilitly of ILs!) into ionic liquids goes far beyond the state of art of nanoparticle synthesis and is expected to have a high technological impact and should offer a way to highly thermodynamically unstable reaction product. Secondly, microwave (MW) irradiation (high polarizability and conductivity of IL ions makes them excellent MW acceptors) of appropriate metal salt/IL solutions should not only lead to NP/IL systems but the reaction of two NP/IL solutions should again lead to otherwise non-accessible reaction products. In combination, new materials with improved properties will be gained. For example, ILs will improve the lifetime of luminescent rare earth (RE)-based systems due to the weaker covalent RE solvent interaction. Analysis and property determinations of the systems under investigation will involve a variety of aspects of chemistry, physics and materials science.

999 848 €

Start date: 2008-09-01, End date: 2013-08-31

For most biologically relevant molecules their chirality is decisive for their function. Within the last two decades asymmetric organo-catalysis has emerged as an environmental benign, metal-free alternative for conventional asymmetric transition metal catalysis. The organo-catalysts, which employ catalyst-substrate interaction motifs commonly found for enzymes, yield unprecedented enantiomeric excesses. Despite the success of these organo-chemical routes, remarkably little is known about the molecular details of the interaction between the catalyst and the substrate. Consequently, there is virtually no rationale method to optimize reaction conditions particularly as related to structure-function relationships. Also the exact nature of the intermediates that induce chirality has remained elusive. The aim of this proposal is to experimentally quantify the formation of reaction intermediates and the nature of intermediate induced chirality that lie at the heart of asymmetric control. This will be achieved by using a combination of advanced spectroscopic techniques. With advanced vibrational spectroscopies (ultrafast two-color and two-dimensional infrared spectroscopy), dielectric spectroscopy, and NMR spectroscopy together with quantum chemical calculations we will quantify structure-dependent interactions: binding geometry, strength of attraction, lifetime of binding, reaction intermediates, and the role of steric repulsion, probed on all timescales relevant to catalytic processes ranging from femtoseconds to seconds. Correlation of such information with the enantiomeric excess obtained in catalytic processes will allow isolating the essential ingredients for stereocontrol. Such molecular-level insights will provide fundamental parameters for optimization of reaction conditions and will initiate the transition from a trial and error approach towards a rational design of new catalytic processes.

1 892 500 €

Start date: 2017-04-01, End date: 2022-03-31

Ultra-short light pulses have become invaluable in time-resolved studies in chemistry and physics. But many important processes are initiated by collisions. While lasers have revolutionized experiments using light pulses, experimentally proven concepts for producing ultra-short pulses of neutral matter are still in their infancy. Hence, our ability to control when a collision occurs is still extremely limited. Recently, we have reported bunch-compression photolysis, the first demonstrated method for producing ultra-short pulses of neutral matter. Here, photolysis of jet-cooled hydrogen iodide is carried out with femto-second laser pulses whose frequency bandwidth has been spatially ordered. Thus, fast H-atom photoproducts overtake slow ones, producing an ultra-short pulse.The central objective of this project is to develop bunch-compression photolysis as a tool for ultrafast timing experiments involving collisions of ultrashort pulses of H-atoms at synchronously photo-excited solid surfaces. Bunch-compression photolysis allows collisions at a surface to be synchronized with photoexcitation on the ps time scale, opening up new ways to study the dynamics of collisions at selectively photo-excited surfaces that have not yet relaxed. Studies on collision dynamics involving excitons produced in 2D semiconductors is one exciting direction for this work. Experiments on synchronized H atom collisions with vibrationally excited surfaces prepared by infrared photoexcitation is another - this enables kinetics experiments with surface site-specificity as well as the direct observation of reaction intermediates. The work and ideas presented here show how to overcome the most challenging barrier to a new class of time-resolved dynamics experiments, opening new frontiers in the study of surface chemistry, where we will begin to understand how selected degrees of freedom of the solid influence collision dynamics and reaction rates.

2 499 356 €

Start date: 2017-10-01, End date: 2022-09-30

Tailoring the chemical reactivity of nanomaterials at the atomic level is one of the most important challenges in catalysis research. In order to achieve this elusive goal, fundamental understanding of the structural and chemical properties of these complex systems must be obtained. Numerous studies have been devoted to understanding the properties that affect the catalytic performance of metal nanoparticles (NPs) such as their size, interaction with the support, and chemical state. The role played by the NP shape on catalytic performance is, however, less understood. Complicating the analysis is the fact that the former parameters cannot be considered independently, since the NP size as well as the support will have an impact on the most stable NP shapes. In addition, the dynamic nature of the NP catalysts and their response to the environment must be taken into consideration, since the working state of a NP catalyst might not be the state in which the catalyst was prepared, but rather a structural and/or chemical isomer that adapted to the particular reaction conditions. To address the complexity of real-world catalysts, a synergistic approach taking advantage of a variety of cutting-edge experimental methods must be undertaken. This project focuses on model heterogeneous catalysts for reactions of tremendous societal and industrial relevance, namely the gas-phase hydrogenation and electrocatalytic reduction of CO2. Important components that are missing from existing studies, and that we propose to contribute, are a systematic design of catalytically active model NPs with narrow size and shape distributions and tunable oxidation state, and in situ and operando structural, chemical, and reactivity characterization of such model catalysts as a function of the reaction environment. The results are expected to open up new routes for the reutilization of CO2 through its direct conversion into valuable chemicals and fuels such as methanol, methane and ethylene.

2 000 000 €

Start date: 2017-05-01, End date: 2022-04-30

The aim of my project is to establish a multidisciplinary platform for quantitative biophysical analysis of protein-protein interactions in health and disease as a basis for drug design: (1) Analyzing protein-protein interactions at the molecular level in healthy systems; (2) Understanding what goes wrong in disease at the molecular level; (3) Development of drugs that will restore the biological system to its healthy conditions. My team will apply this approach to establish the concept of shifting the oligomerization equilibrium of proteins as a therapeutic strategy. I will expand the concepts of allosteric inhibitors and chemical chaperones, and develop the “shiftides”: peptides that shift the oligomerization equilibrium of a protein to modulate its activity, as a new and widely applicable methodology for drug design. I will apply this concept for: (1) inhibiting a protein by binding preferentially to the inactive oligomeric state and shifting the oligomerization equilibrium of the protein towards it; I have demonstrated the feasibility of this approach and developed promising anti-HIV peptides that inhibit the HIV-1 integrase and consequently HIV-1 replication in cells by shifting the integrase oligomerization equilibrium from the active dimer to the inactive tetramer. My team will further develop these peptides, and apply the same approach to inhibit the HIV proteins reverse transcriptase and protease; (2) Activating a protein by binding preferentially to the active oligomeric state and shifting the oligomerization equilibrium towards it: This will be applied for activation of the tumor suppressor p53, by shifting its oligomerization equilibrium from the inactive dimer to the active tetramer. Such shiftides will serve as anti-cancer lead compounds. My project will open new doors in the field of drug design, and at the end of the five-year period will result in a general new methodology to affect protein function for medical purposes.

1 250 000 €

Start date: 2008-07-01, End date: 2013-06-30

"We propose to develop and implement advanced magnetic resonance detection and micro-imaging techniques that will benefit many biophysical, chemical, physical, and medical applications. Magnetic resonance (MR) is one of the most profound observation methods in science. MR includes Nuclear Magnetic Resonance (NMR) and Electron Spin Resonance (ESR). It has a variety of applications ranging from chemical structure determination to medical imaging and quantum computing. From a scientific standpoint, MR was the main focus of at least seven Nobel prizes in physics, chemistry, and medicine. From an industrial standpoint, MR is a multibillion industry focused on a range of medical (MRI) and chemical applications (MR spectrometers). Despite the fact that magnetic resonance was discovered more than 60 years ago, there is still plenty of room for new methodologies and applications. This research will confront some of the most challenging issues that this field has yet to offer, which also contain the greatest potential benefits. This is what we call “The MR Challenge”. We will focus on three key MR issues: sensitivity, image resolution, and affordability. Our first goal is to substantially improve the sensitivity of MR spectroscopy and the resolution of MR micro-imaging. We will put most of our efforts on ESR spectroscopy and on the detection of NMR information through an ESR signal (ENDOR). At ambient conditions our goal is to achieve a sensitivity of ~10^4 electron spins and a resolution of 1 micron; at low temperatures we will approach single electron spin sensitivity and image resolution as high as 10nm. In terms of affordability, our goal is to introduce a small probe that is capable of acquiring NMR spectra from samples located outside the magnet (an ""ex-situ"" probe). We will also design and construct a new family of hand-held 3D NMR imaging probes. The new capabilities would be applied in the field of single cell imaging and biophysics, materials science, and medicine."

1 250 000 €

Start date: 2008-08-01, End date: 2013-07-31