Remote Charge Effects on the Oxygen-Atom-Transfer Reactivity and Their Relationship to Molybdenum Enzymes

We report the syntheses, crystal structures, and characterization of the novel cis-dioxomolybdenum(VI) complexes [Tpm*Mo^VIO₂Cl](MoO₂Cl₃) (1) and [Tpm*Mo^VIO₂Cl](ClO₄) (2), which are supported by the charge-neutral tris(3,5-dimethyl-1-pyrazolyl)methane (Tpm*) ligand. A comparison between isostructural [Tpm*Mo^VIO₂Cl]⁺ and Tp*Mo^VIO₂Cl [Tp* = hydrotris(3,5-dimethyl-1-pyrazolyl)borate] reveals the effects of one unit of overall charge difference on their spectroscopic and electrochemical properties, geometric and electronic structures, and O-atom-transfer (OAT) reactivities, providing new insight into pyranopterin molybdoenzyme OAT reactivity. Computational studies of these molecules indicate that the delocalized positive charge lowers the lowest unoccupied molecular orbital (LUMO) energy of cationic [Tpm*MoO₂Cl]⁺ relative to Tp*MoO₂Cl. Despite their virtually identical geometric structures revealed by crystal structures, the Mo^VI/Mo^V redox potential of 2 is increased by 350 mV relative to that of Tp*Mo^VIO₂Cl. This LUMO stabilization also contributes to an increased effective electrophilicity of [Tpm*MoO₂Cl]⁺ relative to that of Tp*MoO₂Cl, resulting in a more favorable resonant interaction between the molydenum complex LUMO and the highest occupied molecular orbital (HOMO) of the PPh₃ substrate. This leads to a greater thermodynamic driving force, an earlier transition state, and a lowered activation barrier for the orbitally controlled first step of the OAT reaction in the Tpm* system relative to the Tp* system. An Eyring plot analysis shows that this initial step yields an O≡Mo^IV-OPPh₃ intermediate via an associative transition state, and the reaction is ∼500-fold faster for 2 than for Tp*MoO₂Cl. The second step of the OAT reaction entails solvolysis of the O≡Mo^IV-OPPh₃ intermediate to afford the solvent-substituted Mo^IV product and is 750-fold faster for the Tpm* system at -15 °C compared to the Tp* system. The observed rate enhancement for the second step is ascribed to a switch of the reaction mechanism from a dissociative pathway for the Tp* system to an alternative associative pathway for the Tpm* system. This is due to a more Lewis acidic Mo^IV center in the Tpm* system.