Doctor of Philosophy, University of Akron, 2006, Chemistry

The introduction of N-heterocyclic carbenes (NHCs) to organometallic and inorganic chemistry was achieved by the synthesis and isolation of chromium and mercury NHC complexes by Ofele and Wanzlick in 1968. The synthesis and characterization of numerous carbene metal complexes by Lappert et al were a significant contribution to this area of chemistry. NHCs have become an important area of research after the isolation of the first stable carbene by Arduengo in 1991. In chapter 1, the synthesis and biological activities of NHCs and their silver(I) and gold(I) derivatives are discussed. In chapter 2, the synthesis and characterization of an imidazolium-linked cyclophane is discussed as well as its potential use as a medicinal agent. In chapter 3, the synthesis and characterization of a silver(I) NHC complex is reported. The antimicrobial activity of the silver(I) NHC complex is also reported against clinically important bacteria. In chapter 4, the synthesis of a variety of silver(I) NHC complexes and their carbene transfer reactions to gold(I) reagents are reported. The gold(I) NHC complexes are also investigated for their anticancer properties. In chapter 5, the use of urocanic acid as NHC precursor is reported. The synthesis and characterization of the first silver(I) NHC complex derived from biological molecule urocanic acid is discussed as well as its antimicrobial activity.

Committee: Wiley Youngs (Advisor) Subjects: Chemistry, Inorganic

Master of Science (MS), Wright State University, 2020, Chemistry

Separately, N-Heterocyclic carbene and Tetrathiafulvalene compounds show great promise for a variety of applications. N-heterocyclic carbenes exhibit desirable metal bonding characteristics which allow for modulation of the metal center via back-bonding interactions. Additionally, this creates a system of increased bonding strength creating stable complexes. Tetrathiafulvalene exhibits strong redox-active and optical characteristics. These are owed to an increased aromaticity as oxidation of the compound occurs and thus, is stable through a multitude of oxidative states. The marriage of these two functionalization creates a unique opportunity for a “cure-all” compound, able to address many problems the world faces today including, but not limited to, battery energy storage, semiconductor fabrication and even photonic applications. This work successfully synthesized and characterized precursor compounds for a ligand that could fuse these two functionalizations. The most promising, a TTF-BTD styled compound was tested for the redox activity as well as optical absorption characteristics of the compound. Other precursors synthesized, mainly compound 11, 12, 15, and 16 do not yet exhibit these characteristics and thus, both 1H-NMR and 13C-NMR were utilized for characterization of these precursor compounds. More testing in the final proposed synthetic route must be achieved in order to determine its efficacy. However, marriage of these moieties as well as subsequent testing must occur to prove these methods synthetically useful.

Committee: Kuppuswamy Arumugam Ph.D. (Advisor); Eric Fossum Ph.D. (Committee Member); David Dolson Ph.D. (Committee Member) Subjects: Chemistry

Master of Science (MS), Wright State University, 2018, Chemistry

Metal N-heterocyclic carbene (NHC) complexes have recently gained much popularity due to their tunable, steric, and electronic properties. Applications for such versatile molecules include organocatalysis, olefin metathesis, sundry cyclization reactions, and materials chemistry. Redox active NHCs are of special interest due to their ability to alter the electronic properties of the metal centers they are ligated to. In the first chapter, Au(I)-NHC complexes were synthesized and tested for biological activity in human cancer cell lines. Increasing reactive oxygen species (ROS) in cellular systems has proven to be a successful pathway for treating cancer. The redox active group in this case was naphthoquinone which contributed to the oxidative stress applied to the tumor cells. Three Au(I)-NHC complexes were synthesized and analyzed structurally utilizing 1H NMR, 13C NMR, and X-ray crystallography. Biological studies including IC50 cell culture lines and cell proliferation analyses were performed to determine the complexes' efficiency and success as a cancer treatment drug. The second chapter describes a theoretical approach to synthesize a redox active tetrathiafulvalene (TTF) fused with an iridium-NHC complex to serve as a redox switchable catalyst. The first compound in this synthetic route was successfully synthesized and analyzed structurally with 1H and 13C NMR, UV-Vis spectroscopy, and IR spectroscopy. The electrochemical properties were also investigated. Tetrathiafulvalene possesses the ability to undergo multiple one electron reversible redox transformations. This unique characteristic paired with the catalytic properties of iridium-NHC could produce a catalyst capable of accessing three or more catalytic species based upon the oxidation state of TTF.

Committee: Kuppuswamy Arumugam Ph.D. (Advisor); Daniel Ketcha Ph.D. (Committee Member); David Turner Ph.D. (Committee Member) Subjects: Biochemistry; Chemistry; Inorganic Chemistry; Organic Chemistry

Master of Science (MS), Wright State University, 2018, Chemistry

Bacterial resistance to current ß-lactam antibiotics necessitates new therapeutic approaches. Silver-based drugs offer a promising alternative because of their antibacterial properties and minimal bacterial resistance. However, many silver-based antibacterial drugs rapidly release silver ions, limiting the bioavailability of silver ions for a longer period of time. Recently, N-heterocyclic carbenes (NHC) containing silver complexes have become a popular subject of research due to their versatility and the slow release of silver ions under biological conditions. To further enhance the efficacy of silver-NHC drugs, we fused redox-active substituents such as naphthoquinone and ferrocenes to NHCs. Both naphthoquinone and ferrocenes have been shown to increase reactive oxygen species (ROS) under biological conditions that may augment the antibacterial action of redox-active silver-NHC complexes. Herein, we report synthesis and characterization of several redox-active silver-NHC complexes, 1-(ferrocenylmethyl)-3-mesityl-imidazol-2-ylidene silver chloride [(2)AgCl] (compound 6), 1,3-di (ferrocenylmethyl)imidazol-2-ylidene silver chloride [(3)AgCl] (compound 7), bis (1-benzyl-3-mesitylimidazol-2-ylidene) silver chloride [(1)2Ag][Cl], (compound 9), Bis (1-(ferrocenylmethyl)-3-mesityl-imidazol-2-ylidene) silver chloride [(2)2Ag][Cl] (compound 10), Bis (1,3 di(ferrocenylmethyl)imidazole-2-ylidene) silver chloride [(3)2Ag][Cl] (compound 11), and bis (1,3-dimesityl-4,5-naphthoquino-imidazol-2-ylidene) silver chloride [(4)2Ag][Cl] (compound 12). Complexes were identified and confirmed via various analytical techniques, including 1H NMR, 13C NMR, infrared spectroscopy, UV-vis spectroscopy, and single crystal X-ray crystallography. A series of cyclic and differential pulse voltammetry experiments were conducted on the complexes to investigate their electrochemical properties. Complexes [(2)AgCl], [(3)AgCl], [(2)2Ag][Cl], [(2)2Ag][Cl], [(3)2Ag][Cl], and [(4)2Ag][Cl] exhibited redox (open full item for complete abstract)

Committee: Kuppuswamy Arumugam Ph.D. (Advisor); Eric Fossum Ph.D. (Committee Member); Ioana Pavel Ph.D. (Committee Member) Subjects: Chemistry

Master of Gerontological Studies, Miami University, 2017, Gerontology

Ohio has an older population who are more likely to live alone than other states. Older Ohioans are at higher risk of nursing home admission. Additionally, a recent study shows that nursing homes in Ohio have lower quality compared to the rest of the United States. Hence, improving nursing home quality in Ohio is paramount in the field of aging services. The goal of this current study was to identify factors that affect nursing home quality in Ohio using data from the 2013 Biennial Survey of Long-Term Care Facilities in Ohio for Nursing Facilities and 2013 fourth-quarter archived data from the Centers for Medicare and Medicaid Services Five-Star Rating System. Not-for-profit facilities with a low proportion of Medicaid days were more likely to be high performers in Health Inspection, Staffing, and Overall domains. Small facilities were more likely to be high performers in Staffing and Overall domains. Facilities that had no administrator turnover were more likely to be high performers in Health Inspection. Non-chain affiliated facilities performed better in the Staffing domain. Facilities with low STNA retention rates were at higher risk of receiving one- or two- star ratings in Overall. Implications for consumers, policy makers, and providers are discussed.

Committee: Jennifer Kinney (Committee Chair); Jane Straker (Committee Member); Robert Applebaum (Committee Member) Subjects: Gerontology

Master of Gerontological Studies, Miami University, 2012, Gerontology

In 2008, the Centers for Medicare and Medicaid Services (CMS) implemented a five-star rating system of nursing homes in the United States. These star ratings have been widely publicized both by CMS and in the national and state media. Although the components of the star rating system take into account various dimensions of quality, the satisfaction of nursing home residents and their families are not taken into consideration. The current study compares the CMS star rating system to the satisfaction ratings of nursing homes provided by residents and their families throughout the state of Ohio. Findings indicate that the star rating system does not adequately reflect consumer satisfaction and recommend that the star rating system be refined to include a consumer component.

Committee: Robert Applebaum PhD (Committee Chair); Jane Straker PhD (Committee Member); Douglas Noe PhD (Committee Member) Subjects: Aging; Health Care; Public Policy

Doctor of Philosophy, University of Akron, 2012, Chemistry

Since the discovery of the first stable silver N-heterocyclic carbene complex by Arduengo in 1991, the field of silver N-heterocyclic carbene complexes has expanded greatly. These complexes have been studied extensively for use in catalysis, as transmetallation agents, and more recently for pharmaceutical applications. Silver has been used for centuries as an anti-microbial agent, and more recently has been shown to have anti-tumor activity as well. Combination with the easily modified N-heterocyclic carbene ligand yields a drug that can be rationally designed for increased water solubility, increased lipophilicity, or to increase activity. These complexes have shown great results, and will be the main focus of this dissertation. Chapter 1 of this dissertation reviews silver N-heterocyclic carbene complexes as promising antimicrobial agents and the evolution of the field over the past two decades. Chapter 2 discusses the synthesis of a new N-heterocyclic carbene backbone, 4,5,6,7-tetrachlorobenzimidazole, and the corresponding silver complexes for antimicrobial use. These complexes were then examined in vitro against a panel of clinical bacteria, displaying inhibitory concentrations between 0.25-4 µg/mL. Additionally, two of the silver complexes displayed antimicrobial activity against a silver-resistant E. coli strain. Chapter 3 discusses the rational design of several new naphthalene containing imidazolium cations, the precursors to silver N-heterocyclic carbene complexes, for the use as anti-tumor drugs. These new imidazolium cations have been designed to increase water solubility, anti-tumor activity, and encapsulation efficiency into biodegradable delivery devices through modification of the substituents. These cations have demonstrated in vitro anti-tumor activity comparable to cisplatin against three types of lung cancer. The anti-tumor activity increased with the increase in the length of the alkyl chain substituent. Additionally, it was noted that the pos (open full item for complete abstract)

Committee: Wiley Youngs Dr. (Advisor); Claire Tessier Dr. (Committee Member); Michael Taschner Dr. (Committee Member); Peter Rinaldi Dr. (Committee Member); Gerald Young Dr. (Committee Member) Subjects: Chemistry

Doctor of Philosophy, University of Akron, 2007, Chemistry

This dissertation discusses a newly growing area of the synthesis from xanthine ligands of new silver(I) N- heterocyclic carbene (NHC) complexes and their potential antimicrobial use in cystic fibrosis lung infections. In chapter I, the ligand properties of NHCs and the synthetic methods for the formation of silver(I) NHC complexes are outlined. An overview of silver antimicrobials and previously synthesized silver(I) NHC complexes from pyridine linked and tripodal imidazolium salts for the topical applications is discussed. Furthermore, a brief summary of cystic fibrosis is given. Chapter II presents the introductory studies to explore the NHC silver(I) chemistry of caffeine. Formation and characterization of mono and dinuclear bis(NHC) silver(I) complexes from different methylated caffeine salts are given. Chapter III focuses on the formation of an NHC-silver(I) acetate complex from the iodide salt of methylated caffeine. This complex demonstrates a promising antimicrobial activity against numerous resistant respiratory pathogens including members of the Burkholderia cepacia complex which causes a high rate of mortality in patients with cystic fibrosis. Synthesis of NHC silver(I) complexes from theophylline derivatives is given in chapter IV. The antimicrobial activity of these complexes against the same pathogens used in chapter III is presented. In chapter V, the use of a bis(NHC) silver(I) complex from methylated caffeine as a carbene transfer agent is demonstrated and formation of a Rh(I) NHC complex is outlined. Furthermore, the synthesis and characterization of Pt(II) and Pd(II) NHC complexes of methylated caffeine are presented.

Committee: Wiley Youngs (Advisor) Subjects:

Doctor of Philosophy, University of Akron, 2005, Chemistry

The original reports of metal complexes of N-heterocyclic carbenes (NHCs) by Ofele and Wanzlick, the continuing investigations by Lappert, and the isolation of free carbenes by Arduengo provided the foundation to a growing area of chemistry. A recent advance in the area is the use of silver NHC complexes as carbene transfer reagents. The use of silver NHCs as transfer reagents has allowed for the exploration of other less accessible metal NHC systems. To date, metal NHC complexes have primarily been synthesized and used for catalytic functions; however, N-heterocyclic carbenes have begun to be investigated for medicinal use by our group, as well as others. This dissertation discusses the syntheses of imidazolium salts, which are precursors to N-heterocyclic carbenes, as well as the syntheses of a variety of silver NHC complexes. Chapter 1, the introduction, gives an overview of silver NHC chemistry and reports the current syntheses, properties and application of silver NHCs. Chapter 2 focuses on the synthesis and characterization of an imidazolium linked cyclophane and the synthesis of the corresponding silver NHC complex. Chapters 3 and 4 involve the isolation of cationic tetranuclear silver clusters that are stabilized by N-heterocyclic carbenes that have been incorporated into macrocyclic ligands. These complexes are the first examples of N-heterocyclic carbenes bridging two metals. Chapter 5 focuses on the syntheses of imidazolium linked cyclophanes that incorporate other donor groups into the macrocyclic ligands. Also, reported is the synthesis of a cyclophane that has an expanded cavity size that could accommodate larger metals. Also, discussed in Chapter 3 is the beginning of our investigation of silver N-heterocyclic carbenes as potentially useful medicinal reagents. The synthesis of silver NHCs from water is ideal for their application for medicinal use. In chapter 6, we explored the use of silver NHCs in the synthesis of a radiopharmaceutical. The design a (open full item for complete abstract)

Committee: Wiley Youngs (Advisor) Subjects: