Insight into the catalytic mechanism of vanadium haloperoxidases. DFT investigation of vanadium cofactor reactivity.

Density functional theory (DFT) has been used to investigate the catalytic properties of the isolated vanadium cofactor found in vanadium haloperoxidases, with a particular emphasis on the steps going from the resting form of the cofactor to the peroxo complex. Computation of transition states, intermediate species, and UV-vis spectra, as well as comparison of reaction energies, demonstrated the important role of protonation in cofactor activation. This illustrates that the resting form of the vanadium cofactor reacts with hydrogen peroxide according to a mechanism that implies formation of an aqua complex, release of the apical water molecule according to a dissociative pathway, and binding of hydrogen peroxide to vanadium. This process leads to a side-on peroxo species corresponding to the peroxo form observed in the enzyme. In addition, it appears that an acid-base catalysts strongly accelerates the conversion to the side-on peroxo form. The comparison of computed and experimental UV-vis spectra corroborated the proposed reaction pathway and allowed us to explain the effects of the vanadium ligands on the electronic properties of the cofactor.