A series of bi- and tri-dentate amido phosphine ligands H[Ph-PNP] (bis(2-diphenylphosphinophenyl)amine), H[iPr-PNP] (bis(2-diisopropylphosphino- phenyl)amine), H[Cy-PNP] (bis(2-dicyclohexylphosphinophenyl)amine), H[iPr-NP] (N-(2-diphenylphosphinophenyl)-2,6-diisopropylaniline), and H[Me-NP] (N-(2-diphenylphosphinophenyl)-2,6-dimethylaniline) have been synthesized in high yield. Lithiation of these compounds with n-BuLi in ethereal solutions afforded the corresponding lithium complexes. The metathetical reactions of MCl4(THF)2 (M = Zr, Hf) with [iPr-NP]Li(THF)2 or [Me-NP]Li(THF)2 in toluene produced the corresponding [iPr-NP]MCl3(THF) and [Me-NP]2MCl2, respectively, in high yield. In contrast, attempts to prepare [Me-NP]MCl3(THF) and [iPr-NP]2MCl2 led to the concomitant formation of mono- and bis-ligated complexes, from which purification proved rather ineffective. The solution and solid-state structures of [iPr-NP]MCl3(THF) and [Me-NP]2MCl2 were studied by multinuclear NMR spectroscopy and X-ray crystallography. Treatment of PdCl2(PhCN)2 with [iPr-NP]Li(THF)2 in THF afforded dimeric {[iPr- NP]PdCl}2, which was reacted with tricyclohexylphosphine to produce [iPr-NP]PdCl(PCy3). The two phosphorus donors in [iPr-NP]PdCl(PCy3) are mutually cis as indicated by the solution NMR and X-ray crystallographic studies. Both {[iPr-NP]PdCl}2 and [iPr-NP]PdCl(PCy3) are highly active catalyst precursors for Suzuki coupling reactions of a wide array of aryl halides, including those featuring electronically deactivated and sterically hindered characteristics. The metathetical reaction of NiCl2(DME) (DME = dimethoxyethane) with [iPr-PNP]Li(THF) and [Cy-PNP]Li(THF), respectively, produced the diamagnetic nickel complexes [iPr-PNP]NiCl and [Cy-PNP]NiCl. These nickel chloride complexes were reacted with Grignard reagents to afford thermally stable nickel alkyl and aryl complexes [iPr-PNP]NiR and [Cy-PNP]NiR (R = Me, Et, n-Bu, Ph). A series of divalent nickel alkoxo, amido, thiolate complexes [iPr-PNP]NiX and [Cy-PNP]NiX (X = OPh, NHPh, SPh) were also easily prepared. Reaction of H[Ph-PNP] with Ni(COD)2 (COD = cycloocta-1,5-diene) produced the transient [Ph-PNP]NiH, which underwent COD insertion to give [Ph-PNP]Ni(£b1- cyclooctenyl). Instead, reactions of Ni(COD)2 with H[iPr-PNP] and H[Cy-PNP], respectively, afforded isolable diamagnetic complexes [iPr-PNP]NiH and [Cy-PNP]NiH without alkene insertion. The reactivity of these nickel hydride complexes was investigated.

The degradation of phosphate triesters is efficiently catalyzed by organophosphate hydrolases (OPH). While a number of recent studies have focused on optimizing the rate of hydrolysis observed with the native enzyme, no dinuclear complexes that mimic the function of OPH have been reported or investigated. Our present research focuses on the synthesis of dinuclear metal complexes and on the study of their catalytic abilities. An important aspect of this research concerns the investigation of the coordination chemistry of dinuclear ligands designed to hold two metal cations in well defined positions. The ability of the different complexes to catalyze the degradation of thiophosphate triester is presented. Out of several complexes studied, ortho-metallated Pd (II) complexes have been found to display the highest catalytic activity for the hydrolysis of parathion.

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Thesis (Ph. D.)--University of Toledo, 2009. / Typescript. "Submitted as partial fulfillment of the requirements for the Doctor of Philosophy in Chemistry." Includes bibliographical references (leaves 183-217).

Thesis (Ph. D.)--West Virginia University, 2001. / Title from document title page. Document formatted into pages; contains x, 83 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 75-78).

Computational methods have become an integral part of drug development and can help bring new and better drugs to the market faster. The process of predicting the biological activity of large compound collections is known as virtual screening, and has been instrumental in the development of several drugs today in the market. Computational methods can also be used to elucidate the energies associated with chemical reactivity and predict how to improve a synthetic protocol. These two applications of computational medicinal chemistry is the focus of this thesis. In the first part of this work, quantum mechanics has been used to probe the energy surface of palladium(II)-catalyzed decarboxylative reactions in order to gain a better understating of these systems (paper I-III). These studies have mapped the reaction pathways and been able to make accurate predictions that were verified experimentally. The other focus of this work has been to develop virtual screening methodology. Our first study in the area (paper IV) investigated if the results from several virtual screening methods could be combined using data fusion techniques in order to get a more consistent result and better performance. The study showed that the results obtained from data fusion were more consistent than the results from any single method. The data fusion methods also for several target had a better performance than any of the included single methods. Next, we developed a dataset suitable for evaluating the performance of virtual screening methods when applied to large compound collection as a replacement or complement for high throughput screening (paper V). This is the first benchmark dataset of its kind. Finally, a method for using computationally derived reaction coordinates as basis for virtual screening was developed. The aim was to find inhibitors that resemble key steps in the mechanism (paper VI). This initial proof of concept study managed to locate several known and one previously not reported reaction mimetics against insulin regulated amino peptidase.

 A palladium-catalyzed oxidative cascade cyclization reaction has been developed to prepare pyrrolizidine and indolizidine derivatives from simple aliphatic alkenyl amides 2.1ak in one step in moderate to good yields, using Pd(TFA)2 as the catalyst and molecular oxygen (1 atm) as a green oxidant. This cascade cyclization can also proceed for ring-containing unsaturated amides 2.1ln to afford azatricyclic systems. Palladium(II)-catalyzed dehydrohalogenation cascade cyclization reactions have been developed to synthesize polycyclic pyrrolizidine derivatives from iodoalkenylanilides 4.1ai in satisfactory to excellent yields under mild conditions. This reaction produces two stereocenters in one step and only one single diastereomer was obtained in the cyclization of 4.1. The reaction is proposed to proceed through an organopalladium(IV) species, formed by oxidative addition after the aminopalladation. This organopalladium(IV) species then undergoes reductive elimination to give the cyclized product. This cyclization is a fast and efficient way to construct natural alkaloids that contain pyrrolizidine or indolizidine cores. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

Catalyst development is important to the contemporary world as suitable catalysts can allow chemical processes to proceed with reduced energy consumption and waste production. In order to design catalysts with improved performance, the fundamental studies that correlate catalytic properties with surface structures are essential as they can provide mechanistic insights into the reaction mechanism. Pd−Au bimetallic catalysts have shown exceptional performance for a number of chemical reactions, however, the interplay between the reactive species and surface properties are still unclear at the molecular level. In this dissertation, the catalytic chemistry of Pd−Au surfaces was investigated via model catalyst studies under ultrahigh vacuum conditions. A range of Pd−Au model surfaces were generated by annealing Pd/Au(111) surfaces and characterized/tested by surface science techniques. The findings in this dissertation may prove useful to enhance the fundamental understanding of structure-reactivity relation of Pd−Au catalysts in associated reactions.

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Proton exchange membrane fuel cells (PEMFC) are attractive power sources as they offer high conversion efficiencies with low or no pollution. However, several challenges, especially the sluggish oxygen reduction reaction (ORR) and the high cost of Pt catalysts, impede their commercialization. With an aim to search for more active, less expensive, and more stable ORR catalysts than Pt, this dissertation focuses on the development of non-platinum or low-platinum Pd-based nanostructured electrocatalysts and a fundamental understanding of their structure-property-performance relationships. Carbon-supported Pd–Ni nanoalloy electrocatalysts with different Pd/Ni atomic ratios have been synthesized by a modified polyol reduction method, followed by heat treatment in a reducing atmosphere at 500–900 oC. The Pd–Ni sample with a Pd:Ni atomic ratio of 4:1 after heat treatment at 500 °C exhibits the highest electrochemical surface area and catalytic activity. The enhanced activity of Pd80Ni20 compared to that of Pd is attributed to Pd enrichment on the surface and the consequent lattice-strain effects. To improve the catalytic activity and long-term durability of the Pd–Ni catalysts, Pd–Pt–Ni nanoalloys have been synthesized by the same method and evaluated in PEMFC. The Pt-based mass activity of the Pd–Pt–Ni catalysts exceeds that of commercial Pt by a factor of 2, and its long-term durability is comparable to commercial Pt within the testing duration of 180 h. Both the favorable and detrimental effects of Pd and Ni dissolution on the performance of the membrane-electrode assembly (MEA) have been investigated by compositional analysis by transmission electron microscopy (TEM) of the MEAs before and after the fuel cell test. The MEAs of the Pd–Pt–Ni catalyst have then been characterized in-situ by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) to better understand the performance changes during cell operation. The surface state change from Pd-enrichment to Pt-enrichment and the consequent decrease in the charge transfer resistance during cell operation is believed to contribute to the activity enhancement. To further improve the MEA performance and durability, the as-synthesized Pd–Pt–Ni catalysts have been pre-leached in acid and Pd–Pt alloy catalysts have been synthesized to alleviate contamination from dissolved metal ions. Compared to the pristine Pd–Pt–Ni catalyst, the preleached catalyst shows improved performance and the Pd–Pt catalyst exhibits similar performance in the entire current density range. Finally, the catalytic activities for ORR obtained from the rotating disk electrode (RDE) and PEMFC single-cell measurements of all the catalysts are compared. The improvement in the activities of the Pd-Pt-based catalysts compared to that of Pt measured by the RDE experiments is much lower than that obtained in single cell test. In other words, RDE tests underestimate the value of the Pd-Pt-based electrocatalysts for real fuel cell applications. Also, based on the RDE data, the Pd–Pt–Cu catalyst exhibits the highest catalytic activity among all the Pd–Pt–M (M = Fe, Ni, Cu) catalysts studied. / text