Publication Date
2018
Document Type
Thesis
Committee Members
Kuppuswamy Arumugam (Advisor), Eric Fossum (Committee Member), Ioana Pavel (Committee Member)
Degree Name
Master of Science (MS)
Abstract
Bacterial resistance to current [beta]-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 activity attributed to the presence of ferrocene and naphthoquinone moiety. Their antibacterial properties were tested against gram-negative bacterial strains (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) and showed excellent antibacterial properties that are comparable to previously reported silver-NHC complexes. All silver-NHC complexes detailed in this report exhibit MIC and MBC values in the range of 2-12.5 [micro]g/mL. Further mechanistic studies are necessary to elucidate the manner in which these complexes affect bacterial cells.
Page Count
68
Department or Program
Department of Chemistry
Year Degree Awarded
2018
Copyright
Copyright 2018, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.
