Acid-facilitated product release from a Mo(IV) center: relevance to oxygen atom transfer reactivity of molybdenum oxotransferases

Abstract

We report that pyridinium ions (HPyr) accelerate the conversion of [Tp*MoOCl(OPMe)] (1) to [Tp*MoOCl(NCCH)] (2) by 10-fold, affording 2 in near-quantitative yield; Tp* = hydrotris(3,5-dimethyl-1-pyrazolyl)borate. This novel reactivity and the mechanism of this reaction were investigated in detail. The formation of 2 followed pseudo-first-order kinetics, with the observed pseudo-first-order rate constant (k ) linearly correlated with [HPyr]. An Eyring plot revealed that this HPyr-facilitated reaction has a small positive value of ∆S indicative of a dissociative interchange (I) mechanism, different from the slower associative interchange (I) mechanism in the absence of HPyr marked with a negative ∆S . Interestingly, log(k) was found to be linearly correlated to the acidity of substituted pyridinium ions. This novel reactivity is further investigated using combined DFT and ab initio coupled cluster methods. Different reaction pathways, including I, I, and possible alternative routes in the absence or presence of HPyr, were considered, and enthalpy and free energies were calculated for each pathway. Our computational results further underscored that the I route is energetically favored in the presence of HPyr, in contrast with the preferred I-NNO pathway in the absence of HPyr. Our computational results also revealed molecular-level details for the HPyr-facilitated I route. Specifically, HPyr initially becomes hydrogen-bonded to the oxygen atom of the Mo(IV)-OPMe moiety, which lowers the activation barrier for the Mo-OPMe bond cleavage in a rate-limiting step to dissociate the OPMe product. The implications of our results were discussed in the context of molybdoenzymes, particularly the reductive half-reaction of sulfite oxidase.

Remote Charge Effects on the Oxygen-Atom-Transfer Reactivity and Their Relationship to Molybdenum Enzymes

“…These enzymes contain a mononuclear Mo center at their active site and catalyze a wide range of oxidative transformations that are of key importance to human health and global S, C, and N cycles. − We focus on developing an understanding of the molecular-level mechanistic details for OAT reactions mediated by dioxomolybdenum­(VI) centers. In studies of molybdoenzyme model complexes, some of us and others − ,,, have recently noted that specific interactions with Brønsted and/or Lewis acids are capable of accelerating the OAT reaction rates. In the current work, we probe how a single unit of charge difference resulting from a single atom substitution remote from the Mo ion influences the OAT reaction rates.…”