A Biomimetic Approach to Oxidized Sites in the Xanthine Oxidoreductase Family: Synthesis and Stereochemistry of Tungsten(VI) Analogue Complexes

摘要

Two series of square pyramidal (SP) monodithiolene complexes, [M~(VI)O_(3-n)S_n(bdt)]~(2-) and their silylated derivatives [M~(VI)O_(2-n)S_n(OSiR_3)(bdt)]~- (n = 0, M = Mo or W; n = 1, 2, M = W), synthesized in this and previous work, constitute the basic molecules in a biomimetic approach to structural analogues of the oxidized sites in the xanthine oxidoreductase enzyme family. Benzene-1,2-dithiolate (bdt) simulates native pyranopterindithiolene chelation in the basal plane, tungsten instead of the native metal molybdenum was employed in sulfido complexes to avoid autoreduction, and silylation models protonation. The complexes [MO_3(bdt)]~(2-) and [MO_2(OSiR_3)(bdt)]~- represent inactive sites, while [MO_2S(bdt)]~(2-) and [MOS(OSiR_3)(bdt)]~-, with basal sulfido and silyloxo ligands, are the first analogues of the catalytic sites. Also prepared were [MOS_2(bdt)]~(2-) and [MS_2(OSiR_3)(bdt)]~-, with basal sulfido and silyloxo ligands. Complexes are described by angular parameters which reveal occasional distortions from idealized SP toward a trigonal bipyramidal (TBP) structure arising from crystal packing forces in crystalline Et_4N~+ salts. Miminized energy structures from DFT calculations are uniformly SP and reproduce experimental structures. For example, the correct structure is predicted for [WO_2S(bdt)]~(2-), whose basal and apical sulfido diastereomers are potentially interconvertible through a low-lying TBP transition state for pseudorotation. The lowest energy tautomer of the protonated form is calculated to be [WOS(OH)(bdt)]~-, with basal sulfido and hydroxo ligands. Computational and experimental structures indicate that protein sites adopt intrinsic coordination geometries rather than those dictated by protein structure and environment.