Synthesis of nitrogen,sulfur(thiolate) ligands and their metal complexes as models of the active sites of (nitrogen,sulfur)M(II) metalloenzymes

This thesis concerns the synthesis of mixed nitrogen,sulfur(thiolate) NxSy ligands and their FeII, Co II and ZnII metal complexes as models of the active sites of nitrogen, sulfur containing metalloenzymes. Mixed nitrogen/thiolate donor sets are found in the active sites of mononuclear iron enzymes peptide deformylase (PDF) and superoxide reductase (SOR). In order to synthesize structural and functional models of these systems, polydentate NxSy (thiolate) ligands need to be developed. New FeII and Zn II complexes have been prepared using tetradentate N3S(thiolate) and tridentate N2S(thiolate) ligands, and their structural and spectroscopic properties are described. In particular, synthetic efforts have been directed towards metal-hydroxide species with the goal of preparing models of PDF, which employs an MII-OH unit as the active nucleophile in the hydrolysis of formylated substrates. SOR utilizes a novel N4S(thiolate) donor set to catalyze the one-electron reduction of superoxide in anaerobes. The mechanism, number and character of the intermediates formed during this reaction have been the focus of much attention recently. A new synthetic model that mimics the active site of SOR is described, along with its reactivity towards alkylhydroperoxides. Spectroscopic characterization of the transient intermediates thus obtained is also presented. These data provide interesting implications for the intermediate(s) formed during O2- reduction by SOR.; Chapter 1 reviews the active sites of various metalloenzymes, with particular emphasis on nitrogen, sulfur(thiolate) containing enzymes PDF and SOR. The active site structure, catalytically important residues, mechanism and metal ion dependence of PDF and SOR are examined in combination with the current literature on structural and functional model complexes of the enzyme active sites.; The preparation of a series of N2S(thiolate) ligands (L Im2SH, LOMe2SH, and L Dipp2SH) is the focus of Chapter 2. The ligands L IM2SH and LOMe2SH were obtained following similar synthetic procedures and are tripodal in nature. Sterically encumbered LIm2SH was employed in the synthesis of the ZnII complexes (LIm2S)ZnMe and [(LIm2S)2Zn2(mu-OH)(CH 3CN)2](CF3SO3)3. The latter complex was obtained by the reaction of (LIm2S)ZnMe with CF3SO3H. The ligand LDipp2SH was prepared by means of a straightforward one-step synthesis. The reactions of LOMe2SH and LDipp2SH with FeII CoII and ZnII are also discussed providing new insights to rational ligand design.; Chapter 3 describes the chemistry of a tetradentate, mixed nitrogen/alkylthiolate ligand, Py2SH with FeII and CoII. The new mononuclear complexes (Py2S)FeIICl and (Py 2S)FeIIBr were prepared and their structural and spectroscopic properties are presented. The hydroxide-bridged dinuclear and pentanuclear complexes [(Py2S)2Fe2II(mu-OH)](BF 4) and [(Py2S)4FeII5(mu-OH) 2](BF4)4 have been synthesized via aprotic reaction conditions and careful control of L:M stoichiometry. These complexes are rare examples of thiolate-containing iron(II)-hydroxide species. The magnetic behavior of the latter complexes was determined and successfully modeled by a combination of theoretical treatments. In addition, the synthesis and structure of a thiolate-bridged dinuclear CoII complex is shown.; Chapter 4 details the synthesis of a N4S(thiolate)-ligated FeII complex, [([15)aneN4)FeII(SPh)](BF 4), which is a biomimetic model of the N4S(thiolate)-ligated non-heme iron center of SOR. The complex [([15)aneN4)Fe II(SPh)](BF4) reacts with alkylhydroperoxides at low temperatures producing metastable intermediates that were characterized by UV-vis, EPR and resonance Raman spectroscopy. These data show that the intermediates are low-spin FeIII-OOR species with weak Fe-O bonds, in contrast to the existing data for low-spin FeIII-OOR species, which exhibit relatively strong Fe-O bonds. These results suggest that a low-spin FeIII-OO(H) intermediate may occur in SOR, as opposed to previous pr...