The identification and quantification of toxic Hg2+ ions in biological fluids is significant due to its harmful effects. The ion is an exceptional contaminant due to its manifestation in the environment through anthropogenic emissions besides other industrial processes. The bioaccumulation of Hg2+ ions through water bodies, soil and food causes damage to the central nervous system and endocrine glands. This work describes the synthesis of Compd-2 (Compound 2), a thiocarbohydrazide-based UV-active sensor, that can detect Hg2+ and Cu2+ ions in the aqueous medium (HEPES buffer (3 mM) /acetonitrile = 99 : 1, v/v ). Compd-2 responds linearly to the varying concentrations of Hg2+ with a minimum detection limit of 27 nM and a 1 : 1 stoichiometry. H-1 NMR titration with increasing Hg2+ ion concentrations confirmed its interaction by shifting of the peak. In-silico modelling using Gaussian 16.0 and IR spectroscopy verified a single binding site for the Hg2+ ions. Aqueous solubility of Compd-2 was used as an advantage to develop a methodology for the detection and quantification of Hg2+ ions in the human urine sample. The work also demonstrates the nM quantification of Hg2+ ions in the urine sample by the standard addition method.

We present the first examples of CO2 electro-reduction catalysts that feature charged imidazolium groups in the secondary coordination sphere. The functionalized Lehn-type catalysts display significant differences in their redox properties and improved catalytic activities as compared to the conventional reference catalyst. Our results suggest that the incorporated imidazolium moieties do not solely function as a charged tag but also alter mechanistic aspects of catalysis.

A series of ruthenium(II) nitrile hydration catalysts based on the pentadentate ligand 4,7-bis(2′-methyl-2′-mercaptopropyl)-1-thia-4,7-diazacyclononane and its sulfur-oxidized derivatives has been oxidized at the metal center yielding their ruthenium(III) counterparts. Metal-centered oxidation results in complete loss of nitrile hydration activity for the dithiolato (RS−/RS−) parent complex. The sulfur-oxidized thiolato/sulfinato (RS−,RSO2−) derivative displays a decrease in turnover number from 238±23 to 3±1 upon oxidation of Ru(II) to Ru(III). A similar decrease in turnover number from 242±23 to 7±3 is observed upon metal-centered oxidation of the sulfenato/sulfinato (RSO−, RSO2−) derivative. The inactive complex [(4,7-bis(2′-methyl-2′-mercaptopropyl)-1-thia-4,7-diazacyclononane)(triphenyl-phosphine)ruthenium(III)]hexafluorophosphate has been synthesized and characterized by electronic spectroscopy, electron paramagnetic resonance, and single crystal X-ray diffraction studies.

The noninnocent coordinatively saturated mononuclear metal-thiolate complex ReL3 (L = diphenylphosphinobenzenethiolate) serves as an electrocatalyst for hydrogen evolution or hydrogen oxidation dependent on the presence of acid or base and the applied potential. ReL3 reduces acids to H2 in dichloromethane with an overpotential of 380 mV and a turnover frequency of 32 ± 3 s(-1). The rate law displays a second-order dependence on acid concentration and a first-order dependence on catalyst concentration with an overall third-order rate constant (k) of 184 ± 2 M(-2) s(-1). Reactions with deuterated acid display a kinetic isotope effect of 9 ± 1. In the presence of base, ReL3 oxidizes H2 with a turnover frequency of 4 ± 1 s(-1). The X-ray crystal structure of the monoprotonated species [Re(LH)L2](+), an intermediate in both catalytic H2 evolution and oxidation, has been determined. A ligand-centered mechanism, which does not require metal hydride intermediates, is suggested based on similarities to the redox-regulated, ligand-centered binding of ethylene to ReL3.

Kinetic investigations inspired by the metalloenzyme nitrile hydratase were performed on a series of ruthenium(II) complexes to determine the effect of sulfur oxidation on catalytic nitrile hydration. The rate of benzonitrile hydration was quantified as a function of catalyst, nitrile, and water concentrations. Precatalysts L(n)RuPPh3 (n = 1-3; L(1) = 4,7-bis(2'-methyl-2'-mercapto-propyl)-1-thia-4,7-diazacyclononane; L(2) = 4-(2'-methyl-2'-sulfinatopropyl)-7-(2'-methyl-2'-mercapto-propyl)-1-thia-4,7-diazacyclononane; L(3) = 4-(2'-methyl-2'-sulfinatopropyl)-7-(2'-methyl-2'-sulfenato-propyl)-1-thia-4,7-diazacyclononane) were activated by substitution of triphenylphosphine with substrate in hot dimethylformamide solution. Rate measurements are consistent with a dynamic equilibrium between inactive aqua (L(n)Ru-OH2) and active nitrile (L(n)Ru-NCR) derivatives with K = 21 ± 1, 9 ± 0.9, and 23 ± 3 for L(1) to L(3), respectively. Subsequent hydration of the L(n)Ru-NCR intermediate yields the amide product with measured hydration rate constants (k's) of 0.37 ± 0.01, 0.82 ± 0.07, and 1.59 ± 0.12 M(-1) h(-1) for L(1) to L(3), respectively. Temperature dependent studies reveal that sulfur oxidation lowers the enthalpic barrier by 27 kJ/mol, but increases the entropic barrier by 65 J/(mol K). Density functional theory (DFT) calculations (B3LYP/LanL2DZ (Ru); 6-31G(d) (all other atoms)) support a nitrile bound catalytic cycle with lowering of the reaction barrier as a consequence of sulfur oxidation through enhanced nitrile binding and attack of the water nucleophile through a highly organized transition state.

This chapter highlights selected complexes with tetra- and penta-dentate chelates that provide key insights into the oxidized sulfur environment at the enzyme active site. Small-molecule mimics with variable S-oxidation levels provide an attractive method to address these interactions. It discusses a brief history of metal-thiolate sulfur-oxygenation is provided, followed by selected S-oxygenation studies relevant to nitrile hydratase (NHase). The NHase are divided by metal type and organized according to the donor atoms of the chelates. Several ruthenium catalysts have been reported as nitrile hydration catalysts. Ruthenium is also a logical choice for oxidation studies as the second-row transition metal maintains a consistent low spin, which was found to promote S-oxygenation.

A series of Ru(II) catalysts inspired by the metalloenzyme nitrile hydratase catalyze the hydration of benzonitrile with up to 242 turnovers under neutral conditions with very low catalysts loading. Catalysts with an oxidized sulfur environment are less susceptible to product inhibition increasing the catalytic efficiency at low nitrile : water ratios.

The addition of polysubstituted alkenes, alkynes, and dienes to the metal-stabilized thiyl radical complex [Ru-1]+ was evaluated by electrochemical, chemical, and computational methods. The [Ru-1]+ radical complex was generated by two successive one-electron oxidations of the metal thiolate precursor PPN[Ru(DPPBT)3], PPN[Ru-1]−, (PPN=bis(triphenylphosphine)iminium; DPPBT=diphenylphosphinebenzenethiolato). Rate constants were experimentally determined by cyclic voltammetric methods over multiple scan rates using [Ru-1]− solutions containing unsaturated substrates. Rate constants for polysubstituted alkenes range from 1.1×101 to 8.8×102M−1s−1, which are at 3–5 orders of magnitude slower than their monosubstituted counterparts. Rate constants are slower for substituted alkynes varying from 2.3×102 to 1.2×104M−1s−1, which are ∼100 times slower than the corresponding alkenes. Selected complexes were spectroscopically characterized following synthesis by chemical oxidation methods. Addition of asymmetrically substituted alkenes and alkynes yield [Ru-1·substrate]+ products as a mixture of isomers, which were assigned based on 31P NMR and density functional theory calculations (B3LYP/LANL2DZ+6–31g). The solid state structure of [Ru-1·cyclohexene]PF6 was determined by single crystal X-ray diffraction.

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.