Theses and Dissertations from UMD
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Item Trapping Labile Adducts Formed Between an ortho-Quinone Methide and DNA(2012) McCrane, Michael Patrick; Rokita, Steven E; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Exogenously generated electrophiles are capable of alkylating DNA. If not repaired, the resulting DNA adducts can lead to mutations and either cancer or cell death. Electrophilic ortho-quinone methides (o-QM) are reactive intermediates that alkylate DNA and are generated during xenobiotic metabolism of a variety of compounds including environmental toxins and therapeutic agents. Identifying the full alkylation profile of o-QM towards DNA would allow for the genotoxicity of o-QM precursors to be better understood. From model studies based on nucleosides, o-QMs react most readily, but reversibly with the strong nucleophiles 2'-deoxycytidine (dC) N3, 2'-deoxyguanosine (dG) N7, and 2'-deoxyadenosine (dA) N1 and less efficiently, but irreversibly with the weak nucleophiles dG N1, dG N2, and dA N6. The reverse reactions complicate analysis of their products in DNA, which requires enzymatic digestion and chromatographic separation. Selective oxidation by bis[(trifluoroacetoxy)iodo]benzene (BTI) can transform the reversible o-QM-DNA adducts into irreversible derivatives capable of surviving such analysis. To facilitate this analysis, a series of oxidized o-QM-dN adducts were synthesized as analytical standards. Initial oxidative trapping studies with an unsubstituted o-QM and dC demonstrated the necessity of an alkyl substituent para to the phenolic oxygen to block over-oxidation. A novel o-QM included a methyl group para to the phenolic oxygen that successfully blocked the over-oxidation allowing for generation of a stable MeQM-dC N3 oxidized product. Further oxidative trapping studies with MeQM and dG resulted in the formation of three stable MeQM-dG oxidized products (guanine N7, dG N1, and dG N2). Initial studies with duplex DNA optimized the enzymatic digestion and confirmed that the assay conditions were compatible with oxidative trapping. The low yielding MeQM alkylation of duplex DNA needs to be scaled up prior to the oxidative trapping studies. Alternative studies quantified the release of MeQM from DNA with the use of 2-mercaptoethanol as a nucleophilic trap. These studies revealed single stranded DNA as a superior carrier of MeQM than duplex DNA and, therefore, a better target DNA for the oxidative trapping studies due to increased yield of MeQM adducts. With the increased MeQM-DNA yield, the intrinsic selectivity and reactivity of MeQM towards DNA can be determined.Item Synthesis and Reactivity of Monohydrocarbyl Palladium(IV) Complexes Using Hydrogen Peroxide as Oxidant in Protic Solvents(2011) Oloo, Williamson Njoroge; Vedernikov, Andrei N; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Mild, and selective transition metal catalyzed processes for the functionalization of C-H bonds utilizing environmentally benign and inexpensive dioxygen and/ or HOOH oxidants are extremely attractive, as they render these transformations more atom economical and practical for large-scale syntheses. Our approach towards this end involves optimizing the oxidation and C-X reductive elimination steps of the proposed catalytic cycle using tridentate facially chelating ligands, which include 1-hydroxy-1,1-di(2-pyridyl)methoxide, a derivative of di(2-pyridyl)ketone (dpk) and 6-(2-pyridinoyl)pyridine-2-carboxylic acid (ppc). Oxidation of the dpk- and the ppc-ligated palladacycles with HOOH in water and acetic acid solvents produces the corresponding monohydrocarbyl Pd(IV) complexes quantitatively. The mechanism of oxidation of these complexes was investigated, and was proposed to involve addition of HOOH across the C=O bond of the ligand, followed by heterolytic cleavage of the O-O bond via nucleophilic attack of Pd(II) onto the hydroperoxo adduct. The dpk- and ppc-ligated monohydrocarbyl Pd(IV) complexes undergo C-O reductive elimination at room temperature in acetic acid and/ or water to produce the corresponding phenols and/ or aryl acetates quantitatively. Mechanistic studies led us to propose a C-O reductive elimination reaction that proceeds either from a 5-coordinate intermediate, produced upon dissociation of the pyridine group of the dpk chelate or from a 6-coordinate Pd(IV) species. Addition of HX (X=Cl, Br, and I) to aqueous solutions of the dpk-supported hydroxo-ligated monohydrocarbyl Pd(IV) complexes leads to quantitative formation of C-X bond-coupling products. Some of the corresponding X-ligated monohydrocarbyl Pd(IV) complexes were isolated from these solutions (X=Cl and Br), and could be independently prepared by oxidation of the hydrocarbyl Pd(II) precursors with the corresponding N-halogenosuccinimides (NXS). Palladium catalyzed C-H functionalization reactions were performed in the presence of tridentate, facially chelating bis(6-methyl-2-pyridyl)methanesulfonate ligand. Substituted 2-phenylpyridine substrates underwent predominantly C-C coupling reactions with minor C-O coupling products produced, while 2-benzyl- and 2-phenoxypyridine substrates that form 6-membered palladacycles produced the corresponding C-O coupling products selectively in high yields. These reactions were significantly slower in the absence of the ligand, and no reactions took place in the absence of palladium acetate.Item LIGAND-ENABLED PLATINUM--CARBON BOND FUNCTIONALIZATION UTILIZING DIOXYGEN AS THE TERMINAL OXIDANT(2009) Khusnutdinova, Julia; Vedernikov, Andrei N.; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The use of organotransition metal complexes for selective functionalization of hydrocarbons is of great importance. Dioxygen is the most practical oxidant for large-scale applications in the petroleum industry. The focus of this work is the development of ligand-modulated platinum-based systems that can utilize O2 or air for selective transformation of organoplatinum(II) derivatives into alcohols, diols, aminoalcohols and epoxides in aqueous media. We found that the hemilabile tripod ligand dipyridylmethanesulfonate (dpms) enables facile aerobic functionalization of various PtIIMe complexes and some olefin hydroxo PtII complexes in hydroxylic solvents such as water and alcohols. Complexes LPtII(R)(HX) (L = dpms; R = Me, Ph; HX = H2O, MeOH, PhNH2) are oxidized by O2 to yield virtually quantitatively LPtIV(R)(X)(OH). Some of the derived PtIV alkyls LPtIV(Alk)(X)(OH) (X = OH, OMe) can reductively eliminate methanol in high yield. The mechanism of C-O elimination from LPtIV(Me)(X)(OH) (X = OH, OMe) in acidic aqueous media involves two concurrent pathways: an SN2 attack by water and an SN2 attack by a hydroxo or methoxo ligand of another PtIV species. In the latter case dimethyl ether is produced. The complex (dpms)Pt(ethylene)(OH) is oxidized by O2 in water to give a PtIV hydroxyethyl derivative that reductively eliminates ethylene oxide and ethylene glycol in aqueous solutions. The complexes derived from cyclic alkenes, cis-cyclooctene, norbornene, benzonorbornadiene, (dpms)PtII(cy-alkene)(OH), undergo olefin oxoplatination to give 1,2-oxaplatinacyclobutanes (PtII oxetanes). The derived PtII oxetanes are easily oxidized by O2 to produce PtIV oxetanes. The latter eliminate cleanly the corresponding epoxides by the mechanism of direct C(sp3)-O reductive eliminations, unprecedented in organoplatinum chemistry. The 1,2-azaplatinacyclobutanes (PtII azetidines) LPtII(CH2CH2NHR-&kappaC,&kappaN) (R = t-Bu, Me) are oxidized by O2 in the presence of acids to give PtIV azetidine complexes, [LPt(CH2CH2NHR-&kappaC,&kappaN)(OH)]+. The latter undergo reductive elimination of N-alkyl ethanolammonium salts, HOCH2CH2NH2R+, in acidic aqueous solutions at elevated temperatures. Efficient catalytic systems based on palladium acetate, di(6-pyridyl)ketone and 6-methyldi(2-pyridyl)methanesulfonate ligands, suitable for selective oxidation of ethylene with H2O2 to glycol acetates were developed. Glycol acetates were obtained in high selectivity and high yield on H2O2 under mild reaction conditions.Item The Redox Chemistry of Dirhodium Carboxamidates: From Fundamental Structures to Catalytic Functions.(2008-03-24) Nichols, Jason M.; Doyle, Michael P.; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Redox chemistry is the study of molecular structure and function associated with changes in oxidation state. In this manuscript, the structures and functions of dinuclear rhodium complexes in various oxidation states are investigated. In Chapter 1, probing the structural chemistry of dirhodium(II) carboxamidates reveals that an unprecedented, stable, dirhodium(III) complex can be synthesized and characterized. Bis(σ-phenyl)-tetrakis(μ-caprolactamato)dirhodium(III) [Rh2(cap)4Ph2] was prepared from Rh2(cap)4 by a copper catalyzed, aerobic oxidation with aryl transfer from sodium tetraphenylborate. Structural data was obtained by single crystal X-ray diffraction (XRD) of Rh2(cap)4Ph2 and related structures with systematic changes in oxidation state. X-ray photoelectron spectroscopy (XPS) was used to determine binding energies for the rhodium electrons in the complexes. The structural data and XPS binding energies indicate that the Rh-Rh bonding interaction does not exist in Rh2(cap)4Ph2. In Chapter 2, the synthesis of Rh2(cap)4Ph2 was made general by using aryl-boronic acids as the aryl transfer agent. The synthesis provided access to an array of bis(σ-aryl)-Rh2L4 complexes with varying substitution of the aryl ligands. X-ray structures, electrochemical, and computational analysis of complexes with substituents of varying electron-deficiency confirm the Rh Rh bond cleavage. A second-order Jahn-Teller effect is proposed as the basis for the observed Rh-Rh-C bond angle distortions in the X-ray crystal structures. The delocalization of the aromatic π-system through the Rh2-core was investigated and found to be absent, consistent with the calculated electronic structure. The final chapter explores the catalytic redox chemistry of Rh2(cap)4. The mechanism for the oxidative Mannich reaction catalyzed by Rh2(cap)4 in conjunction with tert-butyl hydroperoxide was investigated. This study revealed that iminium ions were formed by the oxidation of N,N-dialkylanilines with the Rh2(cap)4/TBHP system. Rh2(cap)4 was found to be a catalyst for the homolytic decomposition of TBHP to yield the tert-butylperoxyl radical (t BuOO) in a one-electron redox couple. Iminium ions were formed in a stepwise process from N,N-dialkylaniline via rate-limiting, hydrogen atom transfer to t-BuOO followed by rapid electron transfer to excess oxidant in situ. The net hydrogen atom transfer was found to be a step-wise electron transfer/proton transfer between the N,N-dialkylaniline and t BuOO providing evidence for a novel reactivity mode for peroxyl radicals. Nucleophilic capture of the iminium ion to complete the Mannich process was found to occur without association to Rh2(cap)4 under thermodynamic control.Item THE INVESTIGATION OF MERCURY REDOX CHEMISTRY IN NATURAL WATERS AND THE DEVELOPMENT OF A NEW METHOD FOR INCUBATION EXPERIMENTS(2005-04-26) Whalin, Lindsay; Mason, Robert P; Marine-Estuarine-Environmental Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The redox processes that control Hg speciation in natural waters are poorly understood and study results often disagree, primarily a consequence of varied and often flawed methodologies. An incubation method was developed utilizing PFA Teflon® bag reaction vessels to reduce sources of error, and additions of isotopically labeled Hg to quantify rate constants. With low measures of error and duplicate bag reproducibility, this method was applied via incubations of natural waters in ambient sunlight to test three theories; 1) Hg oxidation and reduction are photochemically mediated, 2) Hg reduction is correlated to [DOC], and 3) Hg oxidation is enhanced by halides. The former was proven through the detection of redox chemistry during daylight and its absence in the dark. Results indicate the importance of both redox processes in natural waters, but failed to prove the latter two theories, potentially due to greater than expected [DOC] in one experiment.