Mechanistic Analysis of Nucleophilic Substrates Oxidation by Functional Models of Vanadium‐Dependent Haloperoxidases: A Density Functional Theory Study

Abstract

Density functional theory has been used to investigate the structural, electronic, and reactivity properties of an established functional model for vanadium‐dependent haloperoxidases, K[VO(O2)Hheida] (Hheida2– = 2,2′‐[(2‐hydroxyethyl)imino]diacetate). Possible solution species were determined on the basis of potential exogenous donors present under the conditions necessary for reactivity. The energetically favored solution‐state species is a 1:1 complex of Hheida and vanadium with a coordinated hydroxyethyl donor trans to the vanadium–oxido bond which is in agreement with the reported solid‐state structure for K[VO(O2)Hheida]. Transition states of the oxidation reaction were located for four substrates: chloride, bromide, iodide, and dimethyl sulfide. The role of protonation and its effects on reactivity were examined for each substrate. Protonation of the peroxido moiety leads to a significant drop in the activation barrier for oxidation. In contrast no transition states could be located for an oxido‐transfer process involving the oxido ligand. Barriers of activation calculated for halide oxidation were similar, providing support to the hypothesis that the pKa of the halide in acetonitrile is responsible for the decrease in reactivity between I–, Br–, and Cl–. The results presented herein provide a mechanistic correlation between a functional model and the enzyme, making K[VO(O2)Hheida] a “complete” functional model for vanadium‐dependent haloperoxidase.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Salophen and salen oxo vanadium complexes as catalysts of sulfides oxidation with H2O2: Mechanistic insights

“…Optimized distances between the vanadium center and the coordinated oxygen of the peroxide moiety fall in the range 1.82-2.05Å, while oxygen-oxygen distances of the peroxide group are found between 1.46-1.51Å; both are in good agreement with literature values [45,46]. In general, a decrease of the V O(O) distance is observed increasing the positive charge of the species [45,46].…”

“…It is interesting to notice that the calculated pKa compare reasonably with the values of 5.4-5.9 observed for the vanadium-dependent haloperoxidases enzymes [50,51]. Nevertheless, deprotonated peroxides such as LV V (O)(OO) − are known to be poorly active in oxygen transfer [45,46,49], therefore, even if they could actually be formed in solution according to the pKa values discussed above, they are not the reasonable catalytically active species in the present system. Therefore, the presence of the LV V (O)(OOH) peroxo complexes in solution is the most reliable scenario.…”

“…In general, a decrease of the V O(O) distance is observed increasing the positive charge of the species [45,46]. When the peroxide is protonated (vanadium hydroperoxides), the protonated oxygen is not located at binding distance from the vanadium center, confirming a monodentate mode of coordination of the O O group to the metal; differently, when the peroxide moiety is not protonated both oxygen atoms are coordinated to vanadium, in a Á 2 mode [47].…”

“…The accepted mechanism, already proposed in the literature, for the formation of peroxidic species resulting from the reaction of vanadium species with hydrogen peroxide [43,45,46] has been used as the base to analyze the energetic path leading to the formation of the peroxo species possibly responsible for oxygen transfer, see Scheme 4. In such scheme the original state of the catalyst was considered to be a LV V O + species (L stands for salen or salophen ligand) originated from dissociation of LV V OCF 3 SO 3 in solution; addition of H 2 O 2 to LV V O + to form LV V (OH)(OOH) + species were found to be endothermic processes, with G = +18.1 and +21.4 kcal mol −1 for L = salen and salophen, respectively.…”

Investigating the Vanadium Environments in Hydroxylamido V(V) Dipicolinate Complexes Using 51V NMR Spectroscopy and Density Functional Theory

“…1,2,3 One class of compounds that are insulin enhancing agents are vanadium dipicolinate complexes. 4,5,6,7,8 In these compounds the vanadium likely plays an important role in determining the biological activities 9,10,11 and ligand functionalization can be used to tune the properties of these complexes. 12 The parent five-coordinate dipicolinate vanadium complexes can form adducts with small ligands such as peroxides and hydroxylamines.…”