Can Water Act as a Nucleophile in CO Oxidation Catalysed by Mo/Cu CO‐Dehydrogenase? Answers from Theory

Abstract

The aerobic CO dehydrogenase from Oligotropha carboxidovorans is an environmentally crucial bacterial enzyme for maintenance of subtoxic concentration of CO in the lower atmosphere, as it allows for the oxidation of CO to CO2 which takes place at its Mo−Cu heterobimetallic active site. Despite extensive experimental and theoretical efforts, significant uncertainties still concern the reaction mechanism for the CO oxidation. In this work, we used the hybrid quantum mechanical/molecular mechanical approach to evaluate whether a water molecule present in the active site might act as a nucleophile upon formation of the new C−O bond, a hypothesis recently suggested in the literature. Our study shows that activation of H2O can be favoured by the presence of the Mo=Oeq group. However, overall our results suggest that mechanisms other than the nucleophilic attack by Mo=Oeq to the activated carbon of the CO substrate are not likely to constitute reactive channels for the oxidation of CO by the enzyme.

Unraveling the Reaction Mechanism of Mo/Cu CO Dehydrogenase Using QM/MM Calculations

“…We have not been able to obtain any stable species in which the CO molecule is close to the Cu ion, without being bound to it, allowing CO oxidation through a frustrated Lewis pair (FLP) mechanism, as suggested recently. 23 Thus, our calculations give no support to a FLP mechanism for CO oxidation, in contrast to what was suggested for H 2 oxidation 24 (another interesting reactivity expressed by Mo/Cu-CODH).…”

“…The catalytic mechanism reported here contemplates the formation of the new C–O bond by direct involvement of the catalytically labile oxo ligand of Mo, which was recently evidenced to be the only nucleophile able to promote such a bond-making reaction in Mo/Cu-CODH . The most difficult proposal to be incorporated into the catalytic cycle was the presence of a thiocarbonate intermediate, IntD , in the reaction path.…”

“…Only the large subunit of one dimer ( coxL ), containing the active site, was considered. The setup of the protein was the same as in our previously published works. ,,, This process concerns a detailed analysis of all the protonable residues, studies of the hydrogen-bond pattern, the solvent accessibility, and the possible formation of ionic pairs. The protein was solvated in a sphere of water molecules (with a radius of 60 Å), and a 1 ns simulated-annealing molecular dynamics simulation followed by minimization were run to optimize the added protons and water molecules.…”

Molybdenum‐Copper Antagonism In Metalloenzymes And Anti‐Copper Therapy

“…[46][47][48][49][50] On the basis of the structure of inhibitor n-butyl isocyanide (t-BuNC or CNÀ R) bound CODH complex and in addition to computational studies, the proposed reaction mechanism of oxidation of CO by cofactor is shown in Figure 2. [43,44,46,[48][49][50][51][52][53][54] The bridged sulfide ligand directly participates in the formation of thiocarbonate and is proposed to be an intermediate state for the oxidation of CO in the catalytic cycle. [5,48] In CNÀ R bound structure, no MoÀ SÀ Cu link is observed but thiocarbamate ligand coordinates to Mo by S and O sites and to Cu by N site, thereby Cu site is moving away from the Mo site (Figure 2; A-Cycle).…”

How general is the effect of the bulkiness of organic ligands on the basicity of metal–organic catalysts? H2-evolving Mo oxides/sulphides as case studies

“…All calculations were performed within the framework of density functional theory (DFT) at the BP86-D3(BJ)/def2-TZVP level, [15][16][17][18] an approach which already proved successful for the modelling of Mo complexes in the presence of oxo and sulphide ligands. [19][20][21][22] Calibration of the method employed was also assessed by testing different DFT functionals and basis sets as reported in Table S2 in the Supplementary Information. Geometry optimizations of all models were carried out both in a vacuum and in a water-like solvent, described by the conductor-like polarizable continuum model (C-PCM).…”