ERC FUNDED PROJECTS

Even today, quantum chemical calculations with experimental accuracy are only feasible for small molecules. This statement is especially true if the considered molecule is far from the equilibrium structure, where the overwhelming majority of quantum chemical models break down. The main purpose of this proposal is to develop new quantum chemical methods that are applicable to at least medium-sized molecules and simultaneously provide results sufficiently close to the experimental data and are capable of describing entire potential energy surfaces. The accuracy goal will be achieved through the reduction of the computational cost of high-precision quantum chemical calculations, which are currently practical for molecules of up to 15 atoms. The cost reduction will be accomplished principally by decreasing the number of numerical parameters to be optimized without sacrificing accuracy. To this end, the negligible parameters will be identified and dropped by adopting the corresponding techniques of computer science. The correct behavior of the models for distorted structures will be ensured by developing new approaches that use a linear combination of functions rather than a single function as a starting point for the description of electronic states. Since the programming work associated with the implementation of the proposed schemes is very complex, the project will rely on the automated programming tools previously developed by the proposer. In addition to the outlined challenging tasks, the proposal aims to implement several more straightforward objectives. In particular, the high-accuracy calculations will be extended to molecular properties that are presently not available. Furthermore, the developed methods will be applied to real-life problems, especially in the field of spectroscopy and atmospheric chemistry.

500 000 €

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

The primary aim of this project is to substantially expand the frontiers of current benchmark organocatalytic technology by the design, preparation and evaluation of the first class of thiol-based nucleophilic catalyst capable of emulating the action of NAD+-dependant enzymes such as aldehyde dehydrogenases, which promote the chemoselective oxidation/reduction of aldehyde substrates under mild conditions in aqueous media. The proposed artificial enzymes are designed biomimetically (in the true sense of the word) – only careful examination of the core enzyme competencies, modes-of-action and active sites has guided the design process. One of the key issues which this proposal addresses is the inherent difficulty associated with the design of artificial cofactor-dependent enzymes due to the requirement for a) efficient recognition by the catalyst of both the substrate and the cofactor, and b) the exertion of control over their encounter in the active site. We intend to tackle this challenge by covalently attaching groups functionally equivalent to the catalytically active residues of aldehyde dehydrogenases to a rigid NAD+ analogue in a manner which allows for their synergistic and biomimetic cooperation. Structure determination/mechanistic studies and the application of these new catalysts in a range of oxidations/reductions (we envisage that this project will result in the first organocatalyst able to demonstrably promote either - depending on the reaction conditions), (dynamic) kinetic resolutions, desymmetrisations, and ligations) will be undertaken and the development of catalytic processes for reactions currently outside the scope of any catalytic methodology is a clear long-term goal. We also wish to pursue the application of this potentially groundbreaking nucleophilic catalytic technology (for which no efficient organocatalysts have been thus far reported) toward the selective synthesis of enantiopure building blocks and pharmaceutically relevant molecules.

1 249 772 €

Start date: 2008-10-01, End date: 2014-09-30