Biomedical subjects

Sebastian Kozuch

Publications and source records attributed to Sebastian Kozuch.

3 recordsLinked to original sources

PubMed2006

Does substrate oxidation determine the regioselectivity of cyclohexene and propene oxidation by cytochrome p450?

DFT and QM/MM computations of allylic C-H hydroxylation versus C=C epoxidation in cyclohexene and propene by Compound I of P450cam demonstrate that the relative barriers for the oxidative processes themselves are not good predictors of the observed selectivity. However, a kinetic expression previously developed (Kozuch, S.; Shaik, S. J. Am. Chem. Soc. 2006, 128, 3355) for catalytic cycles under steady-state conditions, predicts, in accord with experiment, that propene will undergo exclusive C=C epoxidation, while cyclohexene will undergo both reactions with a small preference for epoxidation. The model expression for the effective barrier of the cycle forms a general basis for understanding and predicting the selectivity of P450 isozymes.

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PubMed2006

A combined kinetic-quantum mechanical model for assessment of catalytic cycles: application to cross-coupling and Heck reactions.

The efficiency of catalytic cycles is measured by their turnover frequency (TOF). The degree of TOF control determines which states contribute most to the rate of the cycle, and thus indicates the steps that have the highest impact on the cycle. A kinetic model developed by Christiansen (Christiansen, J. A. Adv. Catal. 1953, 5, 311) for catalytic cycles is implemented here in a form that utilizes state energies. This enables one to assess the efficiency of quantum mechanically computed catalytic cycles like the palladium-catalyzed cross-coupling and Heck reactions, to test alternative hypotheses, and to make some predictions. This implementation can also account for effects such as Sabatier's volcano curve for heterogeneous catalysis. The model leads to a dependence of the TOF for any cycle on the "corrected" energy span quantity, deltaE, whose precise expression depends on the location of the summit and trough of the cycle in the step sequence of the cycle. Thus, knowing the highest energy transition state, the most abundant reaction intermediate, and the reaction energy enables one to make quick predictions about relative efficiency of cycles. At the same time, the degree of TOF control determines which states contribute most to the rate of reaction, and thus indicates the values to be included in the calculation of the energetic span and the steps that may be tinkered with to improve the cycle.

Journal Article↗

PubMed2004

Active anionic zero-valent palladium catalysts: characterization by density functional calculations.

This works uses DFT (B3LYP/LACVP*(+)//B3LYP/LACVP* level) to ascertain the existence of the tricoordinate, anionic zero-valent palladium complexes that were postulated as the active species in the catalytic cycles of Pd-catalyzed Heck and cross-coupling reactions. The variety of complexes studied (1 and 2), include [Pd(PR(3))(2)X](-) species, in which R=H, Me, vinyl, and phenyl, and X=Cl, Br, I, AcO, and TFA, as well as bidentate complexes, [Pd[Ph(2)P(CH(2))(n)Ph(2)P]X](-), in which X=Cl, AcO and n=3-6. The study shows that these complexes exist as distinct minima in the gas phase as well as in THF. In addition, it provides geometric features and Pd--X(-) dissociation energies for all these complexes as well as some NMR and IR data, which show a clear distinction in these features between the tri- and dicoordinate Pd(0) species. An orbital interaction model and perturbation theory arguments account for the bonding mechanism and rationalize all the trends in the stability of the Pd--X bond. These trends include the effects of variation of X, R, and the length of the linker in the bidentate ligands.

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