ERC FUNDED PROJECTS

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).

1 253 880 €

Start date: 2013-11-01, End date: 2018-10-31

This programme aims to convert carbon dioxide into high value hydrocarbon products using carbon neutral electrochemical methods. High value products are materials that may be used as carbon based chemical feedstocks and as synthetic fuels, reducing the ever-present demand on oil and natural gas to fulfil these needs. The project is within the remit of an international ambition to valorise carbon dioxide waste and reduce environmentally harmful greenhouse gas generation, as opposed to stopping at carbon capture and sequestration. This proposal outlines an alternative route to carbon dioxide utilisation (CDU), in which a mediated approach that decouples the electrochemical reduction from the catalytic process is explored. Novel bimetallic catalysts will be synthesised and studied, meditating electron donating solutions will be generated, and a robust and comprehensive analytical arrangement will be implemented to allow total identification and quantification of the wide range of possible products. Electrocatalytic CO2 reduction is one of the key approaches to CDU, as it has a direct pathway to carbon neutral renewable electricity. Nonetheless it is a field that has shown minimal progress in the past 30 years. A paradigm shift is necessary in the approach to electrochemical CO2 reduction, where conventional heterogeneous interfacial catalysis is limited by mass transport, passivation, and CO2 solubility. This proposal outlines the use of electron donating mediators generated separately to the catalysed chemical reduction of CO2, such that the electrolyte becomes the electrode. This opens a whole new avenue for catalyst research, and here target bimetallic catalysts that suppress side reactions and promote high value product synthesis are described.

1 499 994 €

Start date: 2018-10-01, End date: 2024-09-30

The implementation of viable practices for the ecologically cognizant production and consumption of energy and renewable resources rank among the most pressing societal challenges of the 21st century. Against this background, the design and development of innovative concepts for the sustainable use of energy and energy-rich compounds from regenerative sources becomes a matter of profound technological and scientific pertinence. A promising approach that has been put forward in the context of chemical synthesis is the application of visible light as an inexpensive source of energy and air as an abundant and gratuitous oxidant for the derivatization of certain hydrocarbons. Despite the enormous economic and ecological benefits associated with the use of light and air as integral components of redox reactions, the realization of such processes is strikingly limited to very isolated applications. Consequently, this methodological deficit represents a momentous opportunity for modern chemical sciences to lastingly transform the routine lines of action for the oxidative manipulation of organic molecules. A key issue that needs to be taken into consideration for the design of efficient light-driven aerobic oxidation protocols is the identification of proper catalyst systems that allow for the site- and chemoselective activation of individual bonds within polyatomic frameworks. In this regard, the prime objective of the proposed research program is the rational design of non-metallic and in part cooperative catalysis regimes as enabling technologies for the electrophilic activation of non-aromatic carbon–carbon multiple- and carbon-chalcogen single bonds to facilitate a wide and diverse array of heretofore unprecedented oxidative coupling-, addition-, and rearrangement reactions. To demonstrate its utility in a superordinate context, this methodological concept will be applied in highly modular enantioselective syntheses of biologically relevant polyketide natural products.

1 499 954 €

Start date: 2019-08-01, End date: 2024-07-31

Hydrogen produced by sunlight is a very promising, environmentally-friendly energy source as an alternative for increasingly scarce and polluting fossil fuels. Since the discovery of hydrogen production by photocatalytic water dissociation on a titanium dioxide (TiO2) electrode 40 years ago, much research has been aimed at increasing the process efficiency. Remarkably, insights into how water is bound to the catalyst and into the dynamics of the photodissociation reaction, have been scarce up to now, due to the lack of suitable techniques to interrogate water at the interface. The aim of this proposal is to provide these insights by looking at specifically the molecules at the interface, before, during and after their photo-reaction. With the surface sensitive spectroscopic technique sum-frequency generation (SFG) we can determine binding motifs of the ~monolayer of water at the interface, quantify the heterogeneity of the water molecules at the interface and follow changes in water molecular structure and dynamics at the interface during the reaction. The structure of interfacial water will be studied using steady-state SFG; the dynamics of the water photodissociation will be investigated using pump-SFG probe spectroscopy. At variable delay times after the pump pulse the probe pulses will interrogate the interface and detect the reaction intermediates and products. Thanks to recent developments of SFG it should now be possible to determine the structure of water at the TiO2 interface and to unravel the dynamics of the photodissocation process. These insights will allow us to relate the interfacial TiO2-water structure and dynamics to reactivity of the photocatalyst, and to bridge the gap between the fundamentals of the process at the molecular level to the efficiency of the photocatalys. The results will be essential for developing cheaper and more efficient photocatalysts for the production of hydrogen.

1 498 800 €

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