Small Molecules

We use quantum mechanical (QM) methods for modelling chemical reactions or to provide predictions of structures where an accurate description of the electron density is important.

• Short Strong Hydrogen Bonds (SSHB): We have been involved in the study of short, strong hydrogen bonds (SSHB) for more than ten years. Based on DFT calculations on a model system, benzoylacetone, we were able to characterize the SSHB in the molecule as having partial covalent character. We were among the first to observe and describe this phenomenon, which has later been identified in many other contexts such as in some high-pressure phases of ice. Recently we analyzed this class of bonds using the theory of Atoms in Molecules and the concept of the Source Function. The results reveal that a simple correlation may not exist between ?-delocalisation and heteroatom distance, as other factors, like steric effects and aromaticity can influence the picture without destroying the short strong hydrogen bond. This suggestion challenges the RAHB concept.
• Low-Barrier Hydrogen Bonds (LBHB): Serine proteases have served as the “battle-ground” for the dispute of low-barrier hydrogen bonds (LBHB) in enzyme catalysis. In the original proposal of LBHB-formation it was suggested that a set of criteria (pKa-equilibration, screened from solvent) has to be fulfilled for LBHB formation. We have challenged these speculative criteria for formation of a LBHB with respect to solvation effects by modeling the effect of implicit and explicit solvation. It was essential to include d-orbitals at the central hydrogen atom and to include implicit solvation by a low dielectric media like in the interior of a protein. Future studies will include detailed analysis of the electron density of the molecular complex, including topological analysis and evaluation of the Source function.
• Transition States of Enzyme Reactions: QM methods are applied for studying the reaction pathways of enzyme reactions. Until now, we have used small model systems of the full enzyme-substrate complex, but future studies will use the better QM/MM method to include the full effect of the protein. Enzymes under study include pyruvate decarboxylase, glycogen phosphorylase, P-type ATPases and serine protases.