A theoretical study of the primary oxo transfer reaction of a dioxo molybdenum(VI) compound with imine thiolate chelating ligands: A molybdenum oxotransferase analogue

The reaction mechanism of an analogue system of the molybdenum oxotransferases was investigated at the density functional (B3P86) level of theory. Kinetic measurements by Schultz and Helm suggest that the reaction MoO2(t-BuL-NS)(2) + X --> MoO(t-BuL-NS)(2) + OX (t-BuL-NS = bis(4-tert-butylphenyl)-2 pyridylmethanethiolate( 1-)) occurs through an associative transition state. Our results on the model reaction, MoO2(SCH2CHNH)(2) + P(CH3)(3) --> MoO(SCH2CHNH)(2) + OP(CH3)(3), support this hypothesis, and indicate that this reaction proceeds through a two-step rilechanism via an associative intermediate. The DeltaH(double dagger) for the first, and rate-determining, step was predicted to be 9.4 kcal/mol, and DeltaH(double dagger) for the second step (release of the OP(CH3)(3) product) was predicted to be 3.3 kcal/mol. These results are in good agreement with the experimental system, for which the rate determining DeltaH(double dagger) = 9.6(6) kcal/mol. Shultz and Helm's experimental model undergoes a significant Ligand rearrangement in the oxo transfer reaction: the reactant, MoO2(t-BuL-NS)(2), has a trans-S arrangement of the ligands, while the product, MoO(t-BuL-NS)(2), has a trans-N arrangement. To investigate the driving force behind the ligand rearrangement, four model compounds, that systematically removed the unsaturation at the N and the chelate character of the ligands, were modeled at the B3P86 level of theory. For all models of the dioxo species, the trans-N isomer was higher in energy than the trans-S isomer. The analysis of these results indicated that a trans influence accounts for approximately 16% of the energy difference, the unsaturation at the nitrogens accounts for approximate to 26%, and the ring strain from the chelator accounts for approximate to 58% of the energy difference between the two isomers (trans-N and trans-S). For all models of the monooxo species, only the trans-N species was a stable geometry. Therefore, for the reverse oxo transfer reaction, ligand rearrangement must occur after or during the attack of the OX substrate.