Master of Science, The Ohio State University, 2021, Chemistry

Carbon-Carbon bond forming reactions are utilized extensively throughout medicinal chemistry. Cross-electrophile coupling (XEC) reactions offer a streamlined way to form C-C bonds avoiding the need to synthesize harsh organometallic reagents prior to their use in a reaction. Recently, out group developed a novel method of electrochemical XEC that utilizes redox mediators as overcharge protectors for Csp2-Csp3 bond formation. The key feature of this reaction is the utilization of redox shuttles as overcharge protectors to prevent the overreduction of metal catalysts in situ. In this work, we expand upon this methodology to include a much wider variety of pyridyl based ligands, including bipyridine, bisoxazoline, and pyridyloxazoline ligands. A variety of redox mediators were also synthesized and spanned across a range of redox potentials which allow for the protection of this new library of catalysts. Electrochemical analysis through cyclic voltammetry (CV) shows that a successful catalyst-shuttle pair can be predicted by matching the onset potentials of each complex. Adoption of these new ligand classes also provides new advantages in the reaction scope depending on the substrates used.

Committee: Christo Sevov (Advisor) Subjects: Chemistry

Doctor of Philosophy, The Ohio State University, 2017, Chemistry

The purpose of this dissertation is to highlight three unique approaches towards discovering a catalytic treatment towards organophosphorus (OP) poisoning. All three potential approaches focus on developing catalytic treatment methods that focus on hydrolyzing OP nerve agents before they can inhibit acetylcholinesterase (AChE). AChE is a serine hydrolase which is responsible for hydrolyzing the neurotransmitter acetylcholine (ACh). AChE operates near diffusion control and can hydrolyze upwards of 25,000 ACh molecules every second. However, when AChE is inhibited by a nerve agent, an excess amount of ACh will build up at neurosynaptic gaps, thereby causing a cholinergic crisis. Once this occurs, a person will start to develop symptoms of muscle contractions, blurry vision, seizures and/or respiratory failure. An OP nerve agent has this effect because it is a structural analog to ACh; however, phosphylation of the active site is more difficult to reverse. Reactivation of AChE can occur by hydrolyzing the phosphylated enzyme with a nucleophile such as 2-PAM (often administered after OP exposure has occurred). Unfortunately, if this reactivation does not occur, the phosphylated enzyme will undergo a spontaneous dealkylation step (termed aging) to give a “dead” enzyme, which to date cannot be reactivated. The first therapeutic design focuses on the research and development of phosphorane haptens. These haptens are conjugated to some mutagen and administered into mice. This causes an immune response and can generate catalytic antibodies which are capable of hydrolyzing the nerve agent VX. In total, ten different haptens were synthesized, mimicking the hydrolysis transition state of VX, and all generated specific antibodies. Each titer of antibodies were then tested against authentic VX samples. The second approach focuses on the development of a combinatorial approach to synthesizing a random library of cyclic peptides. These cyclic peptides are meant to model the activ (open full item for complete abstract)

Committee: Christopher Hadad (Advisor); Jon Parquette (Committee Member); Psaras McGrier (Committee Member) Subjects: Chemistry

Doctor of Philosophy, Case Western Reserve University, 2016, Chemistry

The formation of metal-carbon bonds is central to organometallic chemistry, but traditional procedures typically suffer from hazards or synthetic difficulties. The Gray laboratory has developed protocols for the transmetalation of aryl groups to metal centers from boron by mild methods. By forming s-bonds between metals such as gold to carbons in luminescent organic scaffolds, interesting changes to the photophysics can result, such as long-lived phosphorescence. These organometallics can be used to access other interesting species and have potential for use in light emitting devices and catalysis. Geminally diaurated arenes featuring gold(I)-gold(I) aurophilic interactions supported by semirigid phosphines were obtained from ligand redistribution reactions of digold dichlorides and digold diaryls in the presence of silver salts with weakly coordinating anions. The isolated complexes were characterized by multinuclear NMR spectroscopy, absorption and emission spectroscopies, combustion analysis, and 77 K emission lifetimes, as well as X-ray diffraction crystallography, when possible. Three complexes were crystallographically authenticated. Aromaticity of the geminally diaurated arenes was slightly disrupted. Metallaboroxines, unlike organic boroxines, are a seldom reported class of compounds and rational synthetic methodologies are lacking. Boroxinato gold(III) compounds were obtained in arrested transmetalation reactions of boronic acids and cyclometalated gold(III) trifluoroacetates. The boroxinato gold(III) complexes are the first metallaboroxines characterized by photophysical means, and they displayed phosphorescence with microsecond long lifetimes. Four complexes were crystallographically authenticated. All complexes were characterized by multinuclear NMR spectroscopy, absorption and emission spectroscopies, combustion analysis, 298 K and 77 K emission lifetimes, X-ray crystallography, and relative quantum yields. A silicon analogue was isolated by a simil (open full item for complete abstract)

Committee: Genevieve Sauve (Committee Chair); John Protasiewicz (Committee Member); Malcolm Kenney (Committee Member); Horst von Recum (Committee Member); Thomas Gray (Advisor) Subjects: Chemistry

Doctor of Philosophy, The Ohio State University, 2005, Chemistry

Density functional theory (DFT) calculations were performed to investigate the molecular orbital interactions and the bonding preferences of tris-Cp compounds of zirconium and hafnium. Calculations of the vertical ionization energies of Cp2MCl2 and Cp3MCl (M=Zr, Th) compounds mirror the experimental data observed by PES: Cp2ZrCl2 has a higher first ionization energy than Cp2ThCl2, which is consistent with electronegativity arguments, while Cp3ThCl has a larger first ionization energy than Cp3ZrCl, which is the result of f-orbital stabilization of the 5a2 HOMO in Cp3ThCl. In general, geometry optimizations of a large variety of Cp3MX (M=Zr, Hf; X=halide, H, alkyl, alkoxide, amido) compounds led to the location of two primary structures along the potential energy surface: a 3-5 structure, which exhibits three h5-C5H5 ligands, and a 2-5,1-1 structure, which exhibits two h5-C5H5 and one h1-C5H5 ligands. The binding preference of these structure types have been shown to be dependent upon the p-donor ability of the X ligands. When X has no p-donor ability as in the case of the hydride compounds, the 3-5 structure is more stable for both zirconium and hafnium. When X is a strong p-donor, the 2-5,1-1 structure is more stable for both zirconium and hafnium. When X is a weak p-donor as in the halide compounds, the zirconium complexes prefer the 3-5 geometry while the hafnium complexes prefer the 2-5,1-1 geometry. These structural preferences indicate a competition between the p-donation of the X lone pair and the tris-Cp ligand set. This competition leads to a destabilization of the 15e molecular orbital when X is a strong p-donor; this destabilization causes the 2-5,1-1 structure to be more stable than the 3-5 structure. (MeCp)3HfCl and (MeCp)4Zr were synthesized and fully characterized. Their crystal structures are discussed in light of our theoretical model presented. Solid state dynamics in these systems were also studied via variable-temperature CP-MAS NMR.

Committee: Bruce Bursten (Advisor) Subjects: Chemistry, Inorganic

Doctor of Philosophy, The Ohio State University, 2003, Chemistry

The reaction of open-chain alpha-diketones with omega-alkenyl organometallics, under the proper conditions, led to 1,2-diols bonded to terminal olefinic chains. Exemplified with biacetyl, allylindation in aqueous THF and application of Grignard reagents proceeded readily to give double addition at both adjacent carbonyls respectively. The subsequent ring closing metatheses have been examined. In case of larger ring formations, the diols reacted only if structurally preorganization, capable of facilitating mutual approach of the two double bonds, was present. For this purpose, the prior conversion of diol to a cyclic carbonate was applied. In the latter setting, saponification must precede the diol cleavage step. This chemistry conveniently lends itself to the controlled intercalation of multiple methylene groups between the carbonyl carbons of readily available alpha-diketones to deliver linear or cyclic products. Longithorones A-H, polycyclic natural products structurally expressed as prenylated quinones, were targeted for total synthesis. In the proposed scheme, the preparation of cyclohexene-based core structure via type II enantioselective intramolecular Diels-Alder reaction was anticipated to provide access to each individual target. In diene formation, Stille reaction was extensively studied, in which the organometallic partner was prepared via hydroalumination-transmetallation of alkyne. The oxazolidinone-based chiral auxiliary was attached to the dienophile for the proper stereochemical induction. This attractive approach, however, proved to be unsuccessful. A total synthesis of (+)-epiafricanol has been readily achieved from D-glucose. The tricyclic alcohol target was arrived at by first forming methyl 2-C-methyl-2,3,4-trideoxy-alpha-D-threo-hexopyranoside, followed by extension of the olefinic unit to give the isopropenyl pyranoside, which was subjected to zirconocene-promoted ring contraction to furnish enantiomerically pure substituted cyclopentanol. Upo (open full item for complete abstract)

Committee: Leo Paquette (Advisor) Subjects: Chemistry, Organic