Computers for Chemistry and Chemistry for Computers: From computational prediction of reaction selectivities to novel molecular wires for electrical devices

Taking advantage of cutting-edge technologies in computational and experimental chemistry, my Ph. D. research aimed to bridge both of these chemical subdivisions. Therefore, while part I of this dissertation focuses on new structure-based computational methodologies to predict selectivities of organic and enzymatic reactions, part II is concerned with the design, the synthesis and the electrical properties of novel, single molecular wires. These single molecule technologies described in part II are likely to contribute to more powerful computer chips in the future, which will in turn lead to faster and more accurate computational predictions for chemical problems.;Part I: Computers for Chemistry: Progress towards the design of accurate computational tools to predict the selectivity of chemical reactions . The first fully quantum mechanical study to predict enantioselectivities for a large dataset of organic reactions has been reported. Enantioselectivities were calculated for a diverse set of 46 dioxirane catalyzed epoxidation reactions. Comparison to experiments showed that our methodology is able to accurately predict the free energy differences between transition states leading to enantiomeric products. To further improve the predictive performance, we have also developed a new correction scheme, which increases the accuracy of density functional theory (DFT) for non-covalent interactions. Our new correction scheme accurately estimates interaction energies of non-covalent complexes not only with large, but also with small basis sets at lower computational cost. The improved enantioselectivity prediction protocol containing our latest non-covalent corrections has now been fully automated in a user-friendly fashion. We are currently testing its accuracy for other asymmetric reactions, such as CBS reductions and are also trying to use our methodology to design new asymmetric organocatalysts. In collaboration with Dr. Jianing Li, a structure based computational methodology to predict sites of metabolism of organic substrates with P450 enzymes has also been developed, which is highly relevant for structure-based drug discovery.;Part II: Chemistry for Computers: From novel antiaromatic and pi-pi-stacked molecular wires to highly conducting link groups with direct Au-C bonds. Part II of this dissertation describes studies of antiaromatic and pi-pi-stacked molecular wires as well as new direct ways to connect them to gold electrodes. At the beginning, the first successful single molecule conductance measurements ever on partially antiaromatic molecular wires are described. These wires, based on a biphenylene backbone, were synthesized via a highly regioselective cyclization enabled by the antiaromaticity. Then, two new ways to connect single molecules to gold electrodes with direct Au-C links are presented. The first methodology is based on strained arene rings in [2.2]-paracyclophanes, which were found to directly contact gold electrodes with their pi-systems. The second methodology employs tin based precursors, which get replaced in situ by gold electrodes to also form direct Au-C bonds with very low resistance. The direct Au-C bonds observed with strained paracyclophanes enabled us to study, for the first time, single molecule conductance through multiple layers of stacked benzene rings. Further single molecule conductance studies with less strained stacked benzene rings are currently under way and will provide additional valuable evidence about electron transport in stacked pi-systems.