Functional Analogue Reaction Systems of the DMSO Reductase Isoenzyme Family:  Probable Mechanism of S-Oxide Reduction in Oxo Transfer Reactions Mediated by Bis(dithiolene)−Tungsten(IV,VI) Complexes

Abstract

The recent development of structural and functional analogues of the DMSO reductase family of isoenzymes allows mechanistic examination of the minimal oxygen atom transfer paradigm M(IV) + QO M(VI) O + Q with the biological metals M = Mo and W. Systematic variation of the electronic environment at the WIV center of desoxo bis(dithiolene) complexes is enabled by introduction of para-substituted phenyl groups in the equatorial (eq) dithiolene ligand and the axial (ax) phenolate ligand. The compounds [W(CO)2(S2C2(C6H4-p-X)2)2] (54-60%) have been prepared by ligand transfer from [Ni(S2C2(C6H4-p-X)2)2] to [W(CO)3(MeCN)3]. A series of 25 complexes [W(IV)(OC6H4-p-X')(S2C2(C6H4-p-X)2)2]1- ([X4,X'], X = Br, F, H, Me, OMe; X' = CN, Br, H, Me, NH2; 41-53%) has been obtained by ligand substitution of five dicarbonyl complexes with five phenolate ligands. Linear free energy relationships between E1/2 and Hammett constant p for the electron-transfer series [Ni(S2C2(C6H4-p-X)2)2]0,1-,2- and [W(CO)2(S2C2(C6H4-p-X)2)2]0,1-,2- demonstrate a substituent influence on electron density distribution at the metal center. The reactions [WIV(OC6H4-p-X')(S2C2(C6H4-p-X)2)2]1- + (CH2)4SO [W(VI)O(OC6H4-p-X')(S2C2(C6H4-p-X)2)2]1- + (CH2)4S with constant substrate are second order with large negative activation entropies indicative of an associative transition state. Rate constants at 298 K adhere to the Hammett equations log(k([X4,X']/k[X4,H]) = rho(ax)sigma(p) and log(k[X4,X']/k([H4,X']) = 4rho(eq)sigma(p). Electron-withdrawing groups (EWG) and electron-donating groups (EDG) have opposite effects on the rate such that k(EWG) > k(EDG). The effects of X' on reactivity are found to be approximately 5 times greater than that of X (rho(ax) = 2.1, rho(eq) = 0.44) in the Hammett equation. Using these and other findings, a stepwise oxo transfer reaction pathway is proposed in which an early transition state, of primary W(IV)-O(substrate) bond-making character, is rate-limiting. This is followed by a six-coordinate substrate complex and a second transition state proposed to involve atom and electron transfer leading to the development of the W(VI)=O group. This work is the most detailed mechanistic investigation of oxo transfer mediated by a biological metal.

Electronic Fine‐Tuning of Oxygen Atom Transfer Reactivity of cis‐Dioxomolybdenum(VI) Complexes with Thiosemicarbazone Ligands

“…In addition, if EWGs lower the energy of the transition state by ameliorating negative charge build-up, they give rise to faster reaction rates. Similar observations have previously been made with other ligands, including other tridentate Schiff base ligands, such as those obtained by condensation of substituted salicylaldehydes with ortho-aminobenzenethiol, [17] substituted thiophenolate, [44] substituted dithiolenes, [45] and salan-type ligands. [21,41] A particularly pronounced effect of the NO 2 substituent was also observed by Britovsek and Gibson et al with dioxomolybdenum complexes with para-substituted salan-type ligands.…”

Large Density-Functional and Basis-Set Effects for the DMSO Reductase Catalyzed Oxo-Transfer Reaction

“…The latter two groups have also explained the apparent conflict between theoretical calculations and kinetic experiments regarding the rate-limiting step of the reaction. 16 Hofmann demonstrated that density functional theory (DFT) methods and especially the B3LYP functional performed quite well for this reaction 17 and that all reactive species along the reaction coordinate were most stable in the singlet state. 18 However, they reported an activation barrier of only ~40 kJ/mol.…”

Chiral, Neutral, and Paramagnetic Gold Dithiolene Complexes Derived from Camphorquinone

“…[c] [40] [Ni(Et 2 timdt) 2 ] -0.56 -0.11 +0.78 [41] [Ni(S 2 C 2 Me 2 ) 2 ] -1.16 -0.15 - [42] [Ni(S 2 C 2 Ph 2 ) 2 ] -0.87 -0.045 - [43] [(-bordt) UV/Vis/NIR absorption spectra of the nickel and gold complexes exhibit a strong NIR absorption, characteristic of such complexes ( Table 3). Note that this absorption is observed in the nickel complexes at a longer wavelength than in aryl-substituted complexes, indicating that the latter possess a smaller HOMO-LUMO gap, probably due to an increased delocalization on the aryl moieties.…”