Computational studies on organic reactions and enzyme-inhibitor interactions

In this work, chemical reactions and biochemical systems were investigated using computational calculations. Quantum chemical methods were used to identify reaction pathways and to rationalise selectivity and reactivity. New inhibitors were designed based on molecular docking calculations.In the first part of this thesis, the reaction of hydroxylamines with difluoromethylene-releasing reagents was investigated to explain the unexpected formation of carbamoyl fluorides. Several possible reaction pathways were proposed and compared based on density functional calculations. In the second part, the asymmetric and chemoselective hydrogenation of the olefinic function of α,β-unsaturated ketones catalysed by an iridium-sulfoximine-phosphine catalyst was studied. Different literature-known and new reaction mechanisms were investigated with density functional methods. The results indicate that the iridium remains in the oxidation state +III throughout the complete catalytic cycle. Moreover, the coordination of the olefinic function of the substrate takes place trans to the nitrogen atom of the ligand instead of the phosphorus atom. Based on this reaction mechanism, a quadrant selectivity model was derived.The next part of the thesis concentrates on the origin of the olefin isomerisation side reaction during olefin metathesis with Grubbs-type catalysts. Different active species and potential isomerisation mechanisms were proposed and investigated with density functional theory. The computational results indicate that the decomposition of the metathesis catalyst can lead to the formation of an isomerisation catalyst. In the fourth part, a base-catalysed decomposition reaction of lignin β-O-4 model compounds was investigated. Quantum chemical methods were used to rationalise the formation of several reaction products and the strong influence of the counterion of the base were studied.The last part deals with the in development of small organic molecules as inhibitors of the enzyme ARTD10. Proposed structures were investigated with molecular docking as an in silico screening technique to identify promising structures