Date on Master's Thesis/Doctoral Dissertation


Document Type

Doctoral Dissertation

Degree Name

Ph. D.



Degree Program

Chemistry, PhD

Committee Chair

Grapperhaus, Craig

Committee Co-Chair (if applicable)

Buchanan, Robert

Committee Member

Baldwin, Richard

Committee Member

Kozlowski, Pawel

Committee Member

Willing, Gerold


Oxidation; Sulfur


The current dissertation focuses on the effects of sulfur‒oxidation on nitrile hydration activity of a series of ruthenium(II) complexes inspired by nitrile hydratase (NHase). NHase catalytically hydrates nitriles to amides at a low spin non‒heme Fe(III) or non‒corrin Co(III) metal center. The active‒site employs a N2S3X type donor set using two carboxamido nitrogens and three cofacial cysteinic sulfurs that are present in distinct oxidation states as sulfinate (RSO2¯), sulfenate (RSO¯), and thiolate (RS¯). The apical site is occupied by substrate or solvent. A lack of sulfur‒oxidation renders the enzyme inactive. Three precatalysts, LnRuPPh3 (n = 1‒3), are employed to assess S-oxidation effects on benzonitrile hydration that are derived from pentadentate ligand 4,7-bis(2ʹ- methyl-2ʹ -mercaptopropyl)-1-thia-4,7-diazacyclononane. Catalytic assays were performed in biphasic, pH neutral conditions. For L1RuPPh3 188 ± 32 TONs are observed with an associated TOF of 10 ± 2 h-1. On S-oxidation to L2RuPPh3, TON increases to 238 ± 23 with TOF reaching to 13 ± 1 h-1. Further S-oxidation to L3RuPPh3 results in statistically similar TON (242 ± 23) and TOF (13 ± 1 h-1). The results suggest that S-oxidation enhances nitrile hydration at low nitrile:water ratio and also reduces inhibition offered by the product benzamide. Homogeneous kinetic studies were conducted using DMF as the solvent. The kinetic results suggest that S‒oxidation enhances the nitrile hydration rate constant (k3) by four‒folds from 0.37 ± 0.01 to 1.59 ± 0.12 M-1h-1 for L1RuPPh3 to L3RuPPh3, whereas the water‒nitrile exchange equilibrium constant (K2) exhibits an alternating behavior with values of 21 ± 1, 9.0 ± 0.9, and 23 ± 3 for L1RuPPh3, L2RuPPh3, and L3RuPPh3. The enthalpy of activation (ΔH‡) decreases by 26.8 kJ/mol concomitant with S‒oxidation from L1RuPPh3 to L2RuPPh3. The ΔH‡ for precatalyst L3RuPPh3 is statistically same as that of L2RuPPh3. Interestingly, S‒ oxidation increases the entropic barrier (ΔS‡) by 65 J/(mol.K) from L1RuPPh3 to L2-3RuPPh3. DFT calculations predict a similar decrease in the enthalpic barrier with S-oxidation as observed experimentally. As suggested by DFT studies, Soxidation switches the ligand affinity from water to nitrile, and a nitrile-bound mechanism is proposed for L1-3RuPPh3 complexes as corresponding water-bound intermediate is catalytically inactive.

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