Synthesis of Structural Analogues of the Oxidized Sites in the Xanthine Oxidoreductase Enzyme Family

The oxidized active site of members of the xanthine oxidoreductase enzyme family consists of a pyranopterindithiolene ligand chelated to square pyramidal (SP) Mo(VI) with an apical oxo ligand and basal sulfido and oxo or hydroxo ligands. The first structural analogues of this sites have been synthesized and structurally characterized as [WVIO2S (bdt)]2- for the unprotonated site and [WVIOS(OSiPri3)(bdt)]- for the protonated site in which the silyloxide simulates protonation. Complexes were isolated as Et4N+ salts. The bdt and sulfido ligands occupy basal positions. In addition, (Et4N)2[WVIOS2(S2C2Me2)] was prepared. Density functional theory calculations predict small structural preferences (<1 kcal/mol) for SP structures with basal versus apical sulfido ligands and for SP versus trigonal bipyramidal (TBP) structures (<2 kcal/mol). In the crystalline state, [WVIOS2(S2C2Me2)]- occurs in both (distorted) SP and TBP configurations, presumably stabilized by weak lattice forces (bdt = benzene-1,2-dithiolate(2-)).