Sulfur K-Edge X-ray Absorption Spectroscopy and Density Functional Calculations on Mo(IV) and Mo(VI)═O Bis-dithiolenes: Insights into the Mechanism of Oxo Transfer in DMSO Reductase and Related Functional Analogues

Abstract

Sulfur K-edge X-ray absorption spectroscopy (XAS) and density functional theory (DFT) calculations have been used to determine the electronic structures of two Mo bis-dithiolene complexes, [Mo(OSi)(bdt) 2 ] 1− and [MoO(OSi)(bdt) 2 ] 1− where OSi = [OSiPh 2 t Bu] 1− and bdt = benzene-1,2-dithiolate(2−), that model the Mo(IV) and Mo(VI)=O states of the DMSO reductase family of molybdenum enzymes. These results show that the Mo(IV) complex undergoes metalbased oxidation unlike the Mo(IV) tris-dithiolene complexes, indicating that the dithiolene ligands are behaving innocently. Experimentally-validated calculations have been extended to model the oxo-transfer reaction coordinate using dimethylsulfoxide (DMSO) as a substrate. The reaction proceeds through a transition state (TS1) to an intermediate with DMSO weakly bound, followed by a subsequent transition state (TS2) which is the largest barrier of the reaction. The factors that control the energies of these transition states, the nature of the oxo transfer process, and the role of the dithiolene ligand are discussed.

Large Density-Functional and Basis-Set Effects for the DMSO Reductase Catalyzed Oxo-Transfer Reaction

“…the same as in most previous calculations. 14 The DMSO substrate was explicitly modeled and was converted to DMS during the reaction. This model system is illustrated in Figure 1.…”

“…17 It has also been employed in most of the previous studies. 3,7,11,12,14,15,18 Geometries were fully optimized without symmetry constraints. Harmonic vibrational frequencies were computed to verify the nature of the stationary points.…”

“…7,14,15,18 We started by optimizing the separated substrate DMSO and the active-site model (SR). The latter was square pyramidal with the four S ligands in the square plane, as is shown in Figure 1.…”

Comparison of the Active-Site Design of Molybdenum Oxo-Transfer Enzymes by Quantum Mechanical Calculations

“…24 It has also been employed in most of the previous studies. 3,12,14,15,17,19,23 However, to get a feeling of the stability of the results, all energies were also calculated by singlepoint energy calculations with the pure TPSS functional. 48 The results of these calculations are presented in Tables S1-S6 in the supplementary material (keeping the basis sets and all the corrections to the same as for the B3LYP calculations).…”

The relationship between redox enzyme activity and electrochemical potential—cellular and mechanistic implications from protein film electrochemistry

“…61 Specific contributions made by Mo(W) to the activity-potential relationship may then be resolved by virtue of the systematic differences displayed by isostructural Mo/W complexes; namely, faster rates of oxo-transfer from substrate to W(IV) than Mo(IV) and a lower E m for W than Mo for a given couple. 62,63 NapAB substituted with W (W-NapAB) purifies in the same manner and has the same electrophoretic properties as the Mo containing enzyme indicating that there are minimal differences in the structure and charge of these enzymes. W-NapAB retains the peaked activity-potential relationship of Mo-NapAB but displays a higher ratio of maximal to attenuated activity, Fig.…”