| Post-translationally modified cysteinesulfinate (Cys-SO2 -) and cysteinesulfenic acid (Cys-SOH) are known to play important roles in the catalytic mechanism and activity regulation of the enzyme nitrile hydratase (NHase), a bacterial non-heme iron or non-corrin cobalt enzyme that catalyzes the hydration of nitriles to amides. The coordination environments around the iron type and the cobalt type-NHases centers are identical on the basis of X-ray crystallography studies. The sites are composed of two deprotonated carboxamido nitrogen atoms, from peptide bonds of the protein, and three cysteine sulfur atoms, two of them post-translationally modified to incorporate oxygens. So far no mechanism has been proposed for Fe- and/or Co-NHases that accounts for such post-translational modification. In addition, the activity of the Fe type-NHase shuts down upon nitric oxide binding to its substrate-binding site. In the work presented herein, a previously characterized five coordinate Fe-NHase model, [FeIII(S2Me2N 3(Pr,Pr))]+ (1), will be studied in a effort to understand how an open site influences sulfur oxidation. Its reaction with oxidants such as H2O2 will be shown to lead to the formation of an Fe-sulfenate complex. Its characterization, and relevance to NHase as well as comparisons with its amide analogue [FeIIIS2 Me2NMeN2amide(Pr,Pr)] 2- (3), will also be discussed. Furthermore, the novel Co-NHase model complex [CoIII(N2S2 Me2)tame(S)]2(Et4N)2 (11), that has been synthesized from a ligand that provides an electron rich coordination sphere similar to that in the NHase active site, will be presented. Its unusual coordination environment, reactivity and implications towards understanding how the cobalt vs. iron metal ions influence the post-translational modification of the equatorial cysteines in NHase will also be discussed.;Finally, in order to better understand the possible intermediates and inhibition mechanism of NO-Fe-NHase, iron-nitrosyl chemistry will be explored using a five coordinate Fe(II) model complex. This complex will be shown to react with NO(g) to form an [FeNO]7 type complex, according to the formalism introduced by Enemark and Feltham. Several spectroscopic techniques will be employed to study this novel Fe-nitrosyl complex in an effort to assign formal oxidation states of both the iron center and the NO ligand. Studies regarding the reactivity of this [FeNO]7 complex will be also presented. |
