Thermodynamic Fitness of Molybdenum(IV, VI) Complexes for Oxygen Atom Transfer Reactions, Including Those with Enzymatic Substrates

Article abstract of DOI:10.1021/ja00282a025

The oxygen (oxo) atom transfer hypothesis for the enzymatic oxidation/reduction of generalized substrate X/XO by the molybdenum oxotransferases (hydroxylases) has been further pursued by an investigation of the reactions of the Mo(VI) and Mo(IV) complexes MoO2(L-NS2) and MoO(L-NS2)(DMF) (L-NS2=2,6-bis(2,2-diphenyl-2-thioethyl)pyridinate(2-)), respectively, in DMF solution.Because of steric hindrance, these molecules execute oxo transfer without formation of a binuclear μ-oxo Mo(V) species.MoO(L-NS2)(DMF) was previously found to reduce quantitatively a variety of sulfoxides, including at least one enzyme substrate.Here this complex is shown to reduce, with formation of MoO2(L-NS2), a series of N-oxides including those of pyridine, nicotinamide, adenine, and tribenzylamine, which are enzyme substrates or pseudosubstrates.Ph3AsO is also reduced by this complex.A previous demonstration of the catalytic partial transfer of 18O in nicotinamide N-oxide to uric acid by xanthine oxidase is interpreted as supporting the oxo transfer hypothesis.MoO2(L-NS2) is reduced by PhSH to MoO(L-NS2)(DMF), further indicating the feasibility of thiols as physiological electron donors.A thermodynamic criterion for the ability of a Mo^IVO or Mo^VIO2 complex to reduce or oxidize substrate has been developed on the basis of ΔH values for the reaction X + 1/2O2 -> XO.MoO(L-NS2)(DMF) (21)/MoO2(L-NS2) (22) and MoO(S2CNEt2)2 (20)/MoO2(S2CNEt2)2 (19) are positioned in the reaction series so as to oxidize or reduce (as appropriate) all enzymatic substrates for which thermodynamic data are available.Intermetal oxo transfer reactions of the type MoOL_n + MoO2L'_n -> MoO2L_n + MoOL'_n were investigated with 19-22 and the Schiff base complexes MoO(ssp)(DMF) (18), MoO2(ssp)(DMF) (15), MoO(sap)(DMF) (17), and MoO2(sap)(DMF) (13).These demonstrate the thermodynamic oxo donor order to be S4 (19) > NS2 (22) > ONS (15) > O2N (13); the oxo acceptor order is the reverse.All Mo^IVO complexes in the set are able to reduce Me2SO to Me2S.This is a necessary but not sufficient thermodynamic criterion for a functional oxo transferase site model.Under the oxo transfer hypothesis, a sufficient model requires access to both the Mo^IVO and Mo^VIO2 states at real or effective potentials that can be reached with physiological reductants such that catalysis can be sustained.Evidence is presented that anionic sulfur ligands significantly modulate potentials to values appropriate for catalysis, and that tungsten, having more negative potentials than molybdenum in analogous complexes, is unsuitable for this purpose.