DFT characterization of key intermediates in thiols oxidation catalyzed by amavadin

Amavadin is an unusual octa-coordinated VIV complex isolated from Amanita muscaria mushrooms. The outer-sphere catalytic properties of such a complex toward several oxidation reactions are well known. Nevertheless, a remarkable example exists, in which the VV (d0 ) oxidized form of amavadin is able to electro-catalyze the oxidation of some thiols to the corresponding disulfides through an inner-sphere mechanism (Guedes da Silva et al. J. Am. Chem. Soc. 1996, 118, 7568–7573.) The reaction mechanism implies the formation of an amavadin–substrate intermediate, whose half-life is about 0.3 s. By means of Density Functional Theory (DFT) computations and Quantum Theory of Atoms in Molecules (QTAIM) analysis of the electron density, we have first characterized the stereoelectronic features of the VIV (inactive) and VV (active) states of amavadin. Then, the formation of the VV complex with methyl mercaptoacetate (MMA), which has been chosen as a prototypical substrate, has been characterized both thermodynamically and kinetically. DFT results reveal that protonation of VV amavadin at a carboxylate oxygen not directly involved in the V coordination, favors MMA binding into the first coordination sphere of vanadium, by substitution of the amavadin carboxylate oxygen with that of the substrate and formation of an S–H ◊ ◊ ◊ O hydrogen bond interaction. The latter interaction can promote SH deprotonation and binding of the thiolate group to vanadium. The kinetic and thermodynamic feasibility of the VV –MMA intermediates formation is in agreement, along with electrochemical experimental data, also with the biological role exerted by amavadin. Finally, the presence of an ester functional group as an essential requisite for MMA oxidation has been rationalized