MONONUCLEAR ACTIVE SITES OF MOLYBDOENZYMES: CHEMICAL APPROACHES TO STRUCTURE AND REACTIVITY

Abstract — One of two general classes of molybdoenzymes contains mono— nuclear catalytic sites and effects oxidation or reduction of substrate x/x0 by oxygen atom transfer: X + (0)XO. The reaction LMoO2 + X —3LMo0 + X0 is well established in synthetic systems, and is fre-quently accompanied by dimerization of Mo(VI,IV) complexes to [LMo(V)-0320. A general kinetic analysis allowing determination of oxo-transfer rate constants in systems with p—oxo dimer formation is out— lined. EXAFS results for several enzymes indicate the minimal coordi— nation spheres Mo(VI)02(SR)2 and Mo(IV)0(SR)3 for oxidized and fully reduced forms, respecti'vely. In a synthetic approach to these sites, the ligand pyridine—2,6—bis(1, 1—diphenylethanethiol) (L-N(SH)2) was prepared. Reaction with MoO 2(acac)2 afforded the 5-coordinate trigonal bipyramidal complex Mo02(L-NS2), which was converted to MoO-(L-NS 2 (DMF) with Ph3 P in DMF • In this and other oxo-transfer reac-tions of these complexes, the gem—diphenyl groups sterically suppress dimerization to a OMo(V)-0-Mo(V)0 complex. This reaction is blocked in enzymes by protein structural constraints. MoO(L—NS2)(DMF) and Me2SO react to produce Mo02(L-NS2) and Me25. Substrate saturation kinetics are observed at sufficient Me2SO concentrations. The two reactions were coupled to generate a catalytic sulfoxide reduction/phosphine oxi-dation cycle. In a related reaction, d—biotin—d—sulfoxide is reduced by MoO(L-NS2)(DMF) to d-biotin. Inasmuch as d-biotin-d-sulfoxide reductase is a Mo cofactor—dependent enzyme, this reaction provides a meaningful model for an enzymatic oxo—transfer reaction • Kinetic data for various oxo—transfer reactions are presented and their relevance to enzymatic processes is discussed