Notes Computer Modeling of the Oxygen-atom Transfer Reaction between Hydrogen Sulfite and a Molybdenum(VI) Dioxo Complex Anders Thapper, ² Robert J. Deeth,* ,‡ and Ebbe Nordlander* ,² Inorganic Chemistry 1, Chemical Center, Lund University, Box 124, S-221 00 Lund, Sweden, and Inorganic Computational Chemistry Group, Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K. ReceiVed June 9, 1998 Introduction The molybdenum-containing oxotransferase enzymes catalyze oxygen atom transfer to/from biological substrates in the nitrogen, sulfur and carbon cycles. 1 The active sites of these enzymes contain a dissociable cofactor known as Moco 2 consisting of a molybdenum atom coordinated to a pterin derivative called molybdopterin. The oxidized forms of the enzymes have been shown to contain cis-molybdenum(VI) dioxo units bound to one 3 or two 4 molybdopterins through dithiolene moieties of the pterins. Model studies 5 and 18 O labeling 6 experiments indicate that the molybdenum-containing cofactor mediates the oxygen-atom transfer according to eq 1 where X ) arbitrary substrate and L ) ligand(s). Some hyperthermophilic bacteria contain related tungsten enzymes with similar metal- oxo/pterin cofactors. 7 The sulfite oxidase family consists of sulfite oxidase and assimilatory nitrate reductase. 1 Sulfite oxidase catalyzes the last step in the degradation of sulfur-containing amino acids, the oxidation of sulfite to sulfate. The human, 8 rat, 9 and chicken liver 10 enzymes have been sequenced, and the chicken liver enzyme has been structurally characterized at 1.9 Å resolution. 11 In this structure, the coordination environment of the molyb- denum atom is approximately square pyramidal with an oxo ligand in the axial position at an Mo-O distance of 1.75 Å. The equatorial positions are occupied by the two dithiolene sulfurs of one pterin ligand at Mo-S distances of 2.4 Å, one sulfur from a cysteine residue at 2.5 Å from the molybdenum atom and one water/hydroxide ion with an Mo-O distance of 2.2 Å. 11 Extended X-ray absorption fine structure experiments at the Mo K edge of the oxidized enzyme indicate that the molybdenum is coordinated to two oxo ligands at 1.71 Å and three sulfur atoms at 2.41 Å. 12-14 In the reduced form of the enzyme, only one oxo ligand at 1.69 Å from the metal was detected, while the same number of sulfurs were present at a distance of 2.38 Å. 12-14 This suggests that the enzyme is in the reduced form in the crystal structure. Several complexes have been studied as structural and/or functional models of molybdenum-containing oxotransferases. One of these models, [MoO 2 (mnt) 2 ] 2- [mnt 2- ) 1,2-dicyano- ethylenedithiolate], has been found to be able to perform the biologically relevant reaction of oxidizing hydrogen sulfite to HSO 4 - . 15-17 This reaction has been shown to exhibit a Michae- lis-Menten type of kinetic behavior in an acetonitrile/water mixture. Different mechanisms have been suggested for the reaction. 15-17 Sarkar and co-workers 15,16 have proposed two possible ways that the sulfur atom of hydrogen sulfite may attack the metal atom to form an intermediate formulated as “[MoO 2 (HSO 3 )(mnt) 2 ] 3- ”. The first proposal is an attack in a preequilibrium reaction forming a seven-coordinate intermediate. While the authors do not explicitly state the proposed structure of the seven-coordinate intermediate, we interpret this to be that depicted in Figure 1a. The other proposed pathway 15 involves ² Lund University. ‡ University of Warwick. (1) Hille, R. Chem. ReV. 1996, 96, 2757. (2) Collison, D.; Garner, C. 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N.; Kipke, C. A.; Prince, R. C.; Suede, R. A.; Enemark, J. H.; Cramer, S. P. Biochemistry 1989, 28, 5075. (14) George, G. N.; Garrett, R. M.; Prince, R. C.; Rajagopalan, K. V. J. Am. Chem. Soc. 1996, 118, 8588. (15) Das, S. K.; Chaudhury, P. K.; Biswas, D.; Sarkar, S. J. Am. Chem. Soc. 1994, 116, 9061. (16) Chaudhury, P. K.; Das, S. K.; Sarkar, S. Biochem. J 1996, 319, 953. (17) Lorber, C.; Plutino, M. R.; Elding, L. I.; Nordlander, E. J. Chem. Soc., Dalton Trans. 1997, 3997. Mo VI O 2 L n + X h Mo IV OL n + XO (1) Figure 1. Some possible intermediates for the reaction between [MoO2(mnt)2] 2- and HSO3 - . 1015 Inorg. Chem. 1999, 38, 1015-1018 10.1021/ic980646g CCC: $18.00 © 1999 American Chemical Society Published on Web 02/11/1999