Electronic structure studies of the cis-MOS center of model compounds representative of molybdenum hydroxylase active sites.

摘要

The xanthine oxidase (XO) family of mononuclear molybdenum enzymes catalyzes the oxidative hydroxylation of anti-viral guanine based pro-drugs, aromatic heterocycles such as purines and pteridines, as well as a wide range of simple organics that include both aromatic and aliphatic aldehydes and amides. Unlike other hydroxylases, the XO family of enzymes utilizes water as the sole source of oxygen incorporated into substrate and produce, rather than consume, reducing equivalents. In its fully oxidized form, the XO active site possesses a catalytically essential terminal sulfido ligand oriented cis to a strong field terminal oxo ligand. A combined spectroscopic approach has provided insight into the unique electronic structure of the cis [MOS] 2+ (M = Mo or W) and [MoOs]1+ unit in the model compounds CoCp2[TpPrMoVOS(OPh)], CoCp 2[TpPrMoVOS(OPh-(3,5-di-tert-butyl)], TpPrMoVIOS(OPh), TpPrMo VIOS(OPh-(3,5-di-tert-butyl), TpprMov O-S(OPh-(2-sec-butyl)), TpprMo VO-S(OPh-(p-tert-butyl)), TpPrMo VO-S(naphthalate) where (TpPr = hydrotris(3,5-diisopropylpyrazol-1-yl)borate), and Tp*WVIOS(OPh), Tp*WVIOS(SPh) and Tp*W VIOS(SePh) where (Tp* = hydrotris (3,5-dimethylpyrazol-1-yl) borate). The room temperature electronic absorption spectra of CoCp2[Tp PrMoVOS(OPh)], CoCp2[TpPrMo VOS(OPh-(3,5-di-tert-butyl)], TpPrMo VIOS(OPh), TpPrMoVIOS(OPh-(3,5-di- tert-butyl) are very similar, and the low energy region (<26,000 cm-1) consists of several low intensity bands, which were resolved in the MCD spectra and assigned as Ssigma, v, pi + Ov, sigma→ Mo dxy LMCT transitions. The room temperature electronic absorption spectra of Tp*WVIOS(OPh), Tp*WVIOS(SPh) and Tp*WVIOS(SePh) also consist of Ssigma, v, pi +Ev sigma→ W dxy LMCT transitions (E = ancillary ligand chalcogen). Ligand K-edge X-ray absorption spectroscopy of the oxidized model compounds has shown the average ligand field splitting of the dxy and nearly degenerate dxz,yz orbitals to be approximately 10--12,000 cm-1, with the greater splitting displayed in the tungsten compounds. Ligand field transitions observed in the electronic absorption spectra of the paramagnetic compounds reveal that the Mo dxy-dxz,yz splitting is ∼8,000cm -1 for CoCp2[TpPrMoVOS(OPh)] and CoCp2[TpPrMoVOS(OPh-(3,5-di- tert-butyl)], and ∼11,000 cm-1 for Tp PrMoVOS(OPh-(2-sec-butyl)), Tp prMoVOS(OPh-(p-tert-butyl)), Tp prMoVOS(naphthalate). During the synthesis of the latter compounds, the sulfido inserts at the ortho position of the ancillary ligand ring. Density functional (DFT) calculations of the [MOS]2+ compounds show the &phis;xy orbitals to be composed of ∼30--35% sulfido character, which is in excellent agreement with the calculated and experimentally determined Value for the XO "very rapid" intermediate. The unique electronic structure of the cis-MoOS, as well as the closely related cis-WOS unit, has led to the formulation of a mechanism of hydroxylation in which the substrate need not bind to the molybdenum center, and it is proposed that the reaction is "orbitally" controlled and the substrate activated by overlap of the XO LUMO and substrate HOMO.