Experimental and theoretical studies of TAMLRTM Activators: Pharmaceuticals Degradation, Nuclear Tunneling and Electronic Structure Analysis

My Ph.D. can be summarized as a research journey of combating persistent organic pollutants, characterizing the electronic signature of catalysts for renewable energy generation and catalytically oxidizing active pharmaceutical ingredients and hydrocarbons via a combinatorial avenues of computation, analysis and scientific inference.;The study of eliminating persistent organic pollutants showed hydrocarbons and their halogenated derivatives are very resistant to natural attenuation. Comparing theoretical with experimental studies, the reaction rates of [Fe v(O)(B*)]--1 with ethylbenzene (EtBZ) and its isotope labeled species EtBZ-d10 differ in three respects: (i) the initial [Fev(O)(B*)]--1 decay rate for the substrate EtBZ-d10 is slower than that for EtBZ, (ii) the slope of the In ( k/T) vs. 1/T plot of EtBZ-d10 is smaller than that for EtBZ over the experimental temperature range, and (iii) the extrapolated tan- gents of the kinetic curves give a large, negative intercept difference, Int(EtBZ) - Int(EtBZ-d10) < 0 at the limit 1/T → 0. Theoretical analysis, based on density functional theory calculations of thermodynamic parameters of the reaction species and Bell's model for tunneling through quadratic barriers, shows that (i) and (ii) result from isotope-induced changes in both the zero-point energies and nuclear tunneling, whereas (iii) is exclusively an isotope mass effect on tunneling. The research result points out nuclear tunneling has a significant contribution to the hydrocarbon hydroxylation process. A theoretical model was proposed that can be used to predict absolute rate constants outside the experimental fathomable range.;In the sertraline degradation study, I demonstrated that TAML activators at nanomolar concentrations in water activate hydrogen peroxide to rapidly degrade this persistent API. While all the API is readily consumed, degradation slows significantly at one intermediate, sertraline ketone. The process occurs from neutral to basic pH. The pathway has been characterized through four early intermediates which reflect the metabolism of sertraline, providing further evidence that TAML activator/peroxide reactive intermediates mimic those of cytochrome P450 enzymes. TAML catalysts have been designed to exhibit considerable variability in reactivity and this provides an excellent tool for observing degradation intermediates of widely differing stabilities. Two elusive, hydrolytically sensitive intermediates and likely human metabolites, sertraline imine and N-desmethylsertraline imine, could be identified only by using a fast-acting catalyst. The more stable intermediates and known human metabolites, desmethylsertraline and sertraline ketone, were most easily detected and studied using a slow-acting catalyst. The resistance of sertraline ketone to aggressive TAML activator/peroxide treatment marks it as likely to be environmentally persistent and signals that its environmental effects are important components of the full implications of sertraline use.;Fluoxetine, represents the first member of the serotonin receptor reuptake inhibitors (SSRIs) family and is one of the most successful among all members. Its top prescription record among SSRIs and extra stability leads to prevalent occurrence in the environment. Environmental studies showed that FLX can be toxic to aquatic species at trace level of exposure and disruptive to their neurosystems. Therefore, it is urgent to seek an environmentally friendly solution to diminish the harm FLX can potentially bring to the environment. Treatment with TAML activators and hydrogen peroxide, fluoxetine was shown to be rapidly degraded to harmless endpoints. An elusive intermediate along the degradation pathway was proposed and its fleet fate was studied using DFT calculations. The cascade breakdown feature of FLX under TAMLRTM /H202 treatment inspires green pharmaceutical design. (Abstract shortened by UMI.).