Author ORCID Identifier

Date Available


Year of Publication


Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation


Arts and Sciences



First Advisor

Dr. Samuel G. Awuah


Development of stable gold-based complexes has been a rapidly advancing field due to the popularity of gold complexes, particularly for use in biomedical research and catalytic transformations. Given that auranofin, a gold(I) complex with FDA approval for the treatment of rheumatoid arthritis is used in the clinic, the development of stable gold-based molecules of clinical relevance is urgently needed. Herein are reported, synthetic strategies used for the development of new classes of gold(I) and gold(III) complexes for advancement in mitochondrial modulation for use as chemotherapeutics as well as application to gold catalysis due to the unique geometry of complexes presented within. Mitochondrial structure and function are integral to maintaining mitochondrial homeostasis and are emerging biological targets in aging, inflammation, neurodegeneration, and cancer. Meanwhile, targeting cellular metabolism has emerged as a key cancer hallmark that has led to the therapeutic targeting of glycolysis. The study of mitochondrial structure and its functional implications remain challenging partially because of the lack of available tools for direct engagement, particularly in a disease setting. Furthermore, agents that target dysfunctional mitochondrial respiration for targeted therapy remain underexplored. Both the synthesis and characterization of highly potent organometallic gold(III) complexes supported by dithiocarbamate ligands as selective inhibitors of mitochondrial respiration and a gold-based approach using tricoordinate gold(I) complexes to perturb mitochondrial structure and function for selective inhibition of cancer cells have been elucidated. Mitochondrial targeting and inhibitory effects are characterized using a plethora of both in vitro and in vivo experiments. While developing the tricoordinate framework, the unique geometry led to the pursuit of identifying other applications for these distinct gold(I) complexes. The development of oxidant-free, gold-catalyzed, cross-coupling reactions involving aryl halides have been hampered by the lack of gold catalysts capable of performing oxidative addition at Au(I) centers under mild conditions or without some external oxidant. Expanding gold-catalyzed C-H functionalization with readily available aryl halides complements widely used Pd-catalysis in the construction of complex organic structures containing biaryl scaffolds. Herein, is reported the development of novel tricoordinate gold(I) catalysts, which are supported by N,N-bidentate ligands and ligated by phosphine or arsine ligands for C-H functionalization without external oxidants to form biaryls without homocoupling. The catalytic method is insensitive to air or moisture. Computational investigation into the mechanism suggests an oxidative addition step followed by a C(sp2) – H auration and reductive elimination to afford C – H functionalized products in high yields. The asymmetrical character of the air-stable gold(I) catalyst is critical to facilitating this necessary orthogonal transformation. This study unveils another potential of Au(I) catalysis in biaryl synthesis.

Digital Object Identifier (DOI)

Funding Information

The work was supported by the Center for Pharmaceutical Research and Innovation (National Institutes of Health P20GM130456) from 2020 through 2025, Oberlin College Office of Foundation, Government and Corporate Grants (Grant-in-Aid to Gunnar F. Kwakye) from 2019-2021, University of Kentucky Nuclear Magnetic Resonance Center supported by National Science Foundation (Division of Chemistry-9977388) from 1999 to 2001, University of Kentucky X-ray crystallography facility supported by the Major Research Instrumentation program from National Science Foundation (Division of Chemistry-1625732) from 2016 through 2019, National Cancer Institute Center Core Support Grant (P30CA177558) from 2016 through 2021, and the University of Kentucky Markey Cancer Center (P30CA177558) from 2017 through 2021.