Date on Master's Thesis/Doctoral Dissertation


Document Type

Doctoral Dissertation

Degree Name

Ph. D.



Committee Chair

Grapperhaus, Craig

Author's Keywords

Nitrile hydratase; Catalysis; Thiolate oxygenation; Sulfur oxygenation; Hydrolysis of nitriles; Amides


Nitriles; Catalysis


Nitrile hydratase (NHase) is a metalloenzyme that contains a non-heme iron (III) or non-corin cobalt (III) in a non-redox active role. NHase is used as biocatalyst in the industry for the hydrolysis of nitriles to arnides. The trivalent metal ions are six coordinate with the ligand sphere made up of three cysteines, two amide nitro gens, and a waterlhydroxide or nitrile substrate. Interestingly, the N2S3 active site contains two post-translationally modified cysteine residues, resulting in an unusual thiolato (RS-), sulfenate (RS(O)-), sulfinate (RS(Oh-) donor set. Synthetic work to mimic the unusual donor set by direct oxygenation of a metallodithiolate precursor with dioxygen has been reported by our research group. In this research we have investigated the N2S3 ligand 4,7-bis-methylmercaptopropyl-l-thia-4, 7 -diazacyclononane (brnrnp-TASNi- to systematically probe the metal's influence on sulfur reactivity. As result of this research the ruthenium complex (bmmp-TASN)RuPPh3 (1) reacts with dioxygen to yield (bmmpO2- TASN)RuPPh3 (2), (bmmp-O3-TASN)RuPPh3 (3) and (brnrnp-O4-TASN)RuPPh3 (4). By careful control and optimization of the reaction conditions, high yields and functional synthetic models are obtained. Catalytic activity is reported in 1, 2 and 3 with 85 ± 11 turnover in 18 hours for the formation of benzamide for compound 3.