Bis(dithiolene)molybdenum analogues relevant to the DMSO reductase enzyme family: Synthesis, structures, and oxygen atom transfer reactions and kinetics

A series of dithiolene complexes of the general type [Mo-IV(QR')(S2C2Me2)(2 )](1-) has been prepared and structurally characterized as possible structu ral and reactivity analogues of reduced sites of the enzymes DMSOR and TMAO R (QR' = PhO-, 2-AdO(-),-(PrO-)-O-i), dissimilatory nitrate reductase (QR' = 2-AdS(-)), and formate dehydrogenase (QR' = 2-AdSe(-)). The complexes are square pyramidal with the molybdenum atom positioned 0.74-0.80 Angstrom ab ove the S-4 mean plane toward axial ligand QR'. In part on the basis of a r ecent clarification of the active site of oxidized Rhodobacter sphaeroides DMSOR (Li, H.-K.; Temple, C.; Rajagopalan, K. V.; Schindelin, H. J. Am. Che m. Sac. 2000, 122, 7673), we have adopted the minimal reaction paradigm Mo- IV + XO reversible arrow (MoO)-O-VI + X involving desoxo Mo(IV), monooxo Mo (VI), and substrate/product XO/X for direct oxygen atom transfer of DMSOR a nd TMAOR enzymes. The [Mo(OR')(S2C2Me2)(2)](1-) species carry dithiolene an d anionic oxygen ligands intended to simulate cofactor ligand and serinate binding-in DMSOR and TMAOR catalytic sites. In systems with N-oxide and S-o xide substrates, the observed overall reaction sequence is [Mol(IV)(OR')(S2 C2Me2)](1-) + XO --> [(MoO)-O-VI(OR')(S2C2Me2)(1-) --> [(MoO)-O-V(S2C2Me2)( 2)](1-). Direct oxo transfer in the first step has been proven by isotope l abeling. The reactivity of [Mo(OPh)(S2C2Me2)(2)](1-) has been the most exte nsively studied. In second-order reactions, 1 reduces DMSO and (CH2)(4)SP ( k(2) approximate to 10(-6), 10(-4) M-1 s(-1); DeltaS(double dagger) = -36, -39 eu) and Me3NO (k(2) = 200 M-1 s(-1); DeltaS(double dagger) = -21 eu) in acetonitrile at 298 K. Activation entropies indicate an associative transi tion state, which from relative rates and substrate properties is inferred to be concerted with X-O bond weakening and Mo-O bond making. The (MoO)-O-V I product in the first step; Such as [(MoO)-O-VI(OR')(S2C2Me2)(2)](1-), is an intermediate in the overall reaction sequence, inasmuch as it is too uns table to isolate and decays by an internal redox process to a MoVO product, liberating an equimolar quantity of phenol. This research affords the firs t analogue reaction systems of biological N-oxide and S-oxide substrates th at are based on desoxo Mo(IV) complexes with biologically relevant coordina tion. Ore-transfer reactions in analogue systems are substantially slower t han enzyme systems based on a k(cat/)K(M) criterion. An interpretation of t his behavior requires more information on the rate-limiting step(s) in enzy me catalytic cycles. (2-Ad = 2-adamantyl, DMSOR = dimethyl sulfoxide reduct ase, TMAOR = trimethylamine N-oxide reductase).