Mo-amino acid complexes as analogs for molybdoenzyme: A DFT approach

Abstract

A DFT investigation of hypothesized molybdenum(VI)-amino acid complexes has been considered as a model for xanthine oxidase. All these complexes have been optimized and analyzed by vibrational analysis. The complexes have been subjected to one electron reduction to produce anionic analogs. All complexes and reduced species are optimized in vacuum as well as in water and the associated free energy changes have been estimated. From these changes, the qualitative redox energy has been calculated by thermodynamic cycle which reveals that the complexes are expected to show similar redox behavior. This is also supported by a similar HOMO-LUMO energy gap. The population analysis shows that molybdenum d-orbital contributes >50% to LUMO, suggesting that the oxidation is metal-based in these systems. Also, 30% orbital contribution from sulfido center reveals the possible electronic delocalization through sulfur during oxidation of substrate. As a preliminary step for xanthine oxidation, pyrimidin-4-ol has been studied as a model substrate and the reduced sulfhydryl Mo(V) and sulfido Mo(IV)-substrate intermediates have been optimized with molybdenum in distorted square pyramidal geometry. The bond distances clearly show that Mo-S distance is longer in the sulfhydryl analogue than the sulfide intermediate to support the involvement of hydride transfer in the catalytic cycle. The Mo-C2 (carbon flanked between both the nitrogens) distance of 3.237 Å and the C2-O distance of 1.28 Å are comparable with values reported for the Mo-imidazole intermediate. This study proposes that the hydroxyl oxygen is being inserted in the C-H bond of the substrate to afford pyrimidin-2,4-diol as the product.