Date of Award

Summer 8-18-2023

Level of Access Assigned by Author

Open-Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Advisor

Mitchell R.M. Bruce

Second Committee Member

Alice E. Bruce

Third Committee Member

Matthew Brichacek

Additional Committee Members

Carl Tripp

William Gramlich

Abstract

Gold(I) thiolate complexes have received a lot of interest in drug development due to their promising antiarthritic, antimicrobial, and antitumor properties. Among them, auranofin [(tetra-O-acetyl-D-glucopyranosyl)-thio(triethyl phosphine)-gold(I)] which was approved for the treatment of rheumatoid arthritis in 1985, is an important, medicinally active compound. Recently, researchers have focused on repurposing auranofin for other medicinal applications, as well as developing alternative phosphine gold(I) thiolate complexes for medicinal purposes.

This thesis presents the synthesis and characterization of a series of twelve phosphine gold(I) thiolate complexes of the general formula, R3PAuSR’ where R= phenyl or tri(2-furyl) and SR’ = (2-pyridyl thiol, 2, 2’-mercaptopyrimidine thiol, 4-(methyl)pyrimidine-2-thiol, 4-(trifluoromethyl)pyrimidine-2-thiol, 4, 6-dimethyl-2-pyrimidinethiol, 4-(methyl)benzene-1-thiol, or , 4-(nitro)benzene-1-thiol. The complexes were characterized by elemental analysis, 1H, 13C, and 31P NMR, FT-IR, and ESI-MS. X-ray crystallographic structures were determined for eight of the complexes. Electrochemical data are presented to investigate the anodic process in the phosphine gold(I) thiolate complexes, and mediation studies were used to probe the barrier for electrochemical oxidation in selected complexes. The phosphine gold(I) thiolate complexes undergo a broad irreversible oxidation between +0.6 and +1.2 V vs. Ag/AgCl. It is notable that the slight variation in electronic properties of the thiolate ligands used in the series of complexes produces such a wide range of oxidation potential (ca. 600 mV). Cyclic voltammetry and bulk electrolysis experiments are consistent with an n = 0.5 process for the first oxidation wave in all the complexes, indicative of an EC mechanism. The Randles-Sevcik equation was used to fit cyclic voltammetry data and estimate the E1/2 values.

Ferrocene and 4-nitrophenylferrocene were studied as mediators of the oxidation of phosphine gold(I) thiolate complexes. The results indicate that all of the complexes can be meditated in solution to lower the overpotential that appears at an electrode. The results suggest possible ways that electrons may be ‘gated’ for metal-sulfur redox couples. Evaluation of the antimicrobial activities of the phosphine gold(I) thiolates was conducted in collaboration with CO-ADD (Community for Open Antimicrobial Drug Discovery), The University of Queensland, Australia. Cytotoxicity studies on several breast cancer cell lines were conducted in collaboration with scientists at Baylor University.

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