Publication Date

2024

Document Type

Dissertation

Committee Members

Kuppuswamy Arumugam, Ph.D. (Advisor); Steven R. Higgins, Ph.D. (Committee Member); Jeremy Erb, Ph.D. (Committee Member); Ravi P. Sahu, Ph.D. (Committee Member); Ioana E. Pavel, Ph.D. (Committee Member)

Degree Name

Doctor of Philosophy (PhD)

Abstract

Gold has long been recognized for its medicinal applications, dating back centuries. The use of N-heterocyclic carbenes (NHCs), stable, tunable ligands, has revolutionized the development of metal complexes, particularly those involving gold. Among these, Au-NHC complexes have shown significant promise in treating various diseases, especially arthritis and cancer. More recently, our research has focused on synthesizing dual-targeting naphthoquinone-annulated NHC-based gold(I) complexes, which have demonstrated impressive therapeutic potential in cancer treatment. This emphasizes the growing importance of gold-based complexes in developing more selective and effective cancer therapies. By strategically tuning the electronic and steric properties of these complexes, we have explored a variety of functionalized naphthoquinone-annulated NHCs. In Chapter 1, we detail the synthesis of two isomers of nitro-functionalized naphthoquinone-annulated NHC precursors (imidazolium salts). The successful synthesis of these compounds was confirmed through various characterization techniques, including 1H and 13C NMR and FT-IR spectroscopy. We also investigated the electrochemical properties of these NHC precursors (imidazolium salts), to better understand their redox chemistry. In Chapter 2, we expanded our study by complexing the newly generated NHCs with iridium metal centers to examine their electronic and electrochemical properties. NHC-iridium cyclooctadiene (Ir-COD) and NHC-iridium carbonyl complexes were synthesized for this purpose. The introduction of nitro groups at two distinct positions on the ligands led to noticeable variations in their electrochemical behavior. Additionally, FT-IR spectroscopy was used to examine the carbonyl stretching frequencies of the Ir(CO)₂Cl complexes. The values obtained from IR provided significant insights into the donating abilities of newly generated NHCs. This was further quantified through Tolman Electronic Parameter (TEP) value calculations. Building on these findings, we synthesized a new class of gold complexes featuring a nitro-functionalized naphthoquinone annulated NHC ligand. These complexes are expected to exhibit potent anticancer activity and may be advantageous for potential post-functionalization studies, allowing further modifications to optimize their therapeutic effects. To evaluate their structural and electronic properties, single crystals of the gold complexes were grown, enabling detailed analysis through techniques such as X-ray diffraction. The complexes were comprehensively characterized using various methods, including 1H, 13C NMR, HR-mass spectrometry, X-ray diffraction, cyclic voltammetry, differential pulse voltammetry, and FT-IR spectroscopy. These studies highlight the potential of gold-based NHC complexes as a promising avenue for developing advanced cancer treatments, offering therapeutic efficacy and flexibility for future modifications.

Page Count

168

Department or Program

Department of Earth and Environmental Sciences

Year Degree Awarded

2024

ORCID ID

0009-0002-4229-9680


Share

COinS