Date of Award

Fall 12-16-2022

Level of Access Assigned by Author

Open-Access Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Advisor

Alice E. Bruce

Second Committee Member

Mitchell R. M. Bruce

Third Committee Member

Touradj Solouki

Additional Committee Members

Matthew Brichacek

Michael Kienzler

Abstract

This thesis describes the synthesis and reactivity of heterometallic complexes containing medicinally active Au(I) and tetrathiomolybdate, [MoS4]2-. The research is motivated by the idea of multifunctional drugs, which are designed to treat diseases through two or more mechanisms of action. Five clusters of the general form, [MoS4(AuL)2] were prepared: C-1 (L=IPr), C-2 (L=IBzMe), C-3 (L=IMes), C-4 (L=PPh3), and C-5 (L=PEt3). The clusters with NHC ligands, C-1, C-2, and C-3 were prepared for the first time and thoroughly characterized by 1H NMR,13C{1H} NMR, UV-vis, cyclic voltammetry, SCXRD, elemental analysis and mass spectrometry. C-4 and C-5, which were reported previously, were prepared to compare the effect of phosphine and NHC ligands on the cluster reactivity.

Percent buried volume (% Vbur) calculations show that the steric bulkiness of the ligands increases in the order, C-5 > C-2 > C-4 > C-3 > C-1. A DFT calculation carried out on C-1 suggests the presence of Au-Mo interactions, which could contribute to stabilization of the clusters in addition to the bridging sulfides. The TDDFT study showed that the lowest energy transitions are primarily υ((Au, S) to Mo) and υ(S to Mo) charge transfer. This is consistent with the experimental UV-vis spectra of all five clusters which have lambda max = 487-491 nm.

Clusters C-1 – C-5 were screened for antimicrobial activity by CO-ADD lab at the University of Queensland, Australia. C-2 showed notable activity against one fungal strain, Candida albicans, and C-5 showed notable activity against the gram-positive bacteria, methicillin-resistant Staphylococcus aureus and one fungal strain, Cryptococcus neoformans.

The reactivity of [MoS4(AuL)2] clusters with PhSH and PhSeH in DMSO-d6 was investigated as a model for thiol- and selenol nucleophiles present in cysteine and selenocysteine proteins. In general, the clusters react with PhSH to a greater extent than with PhSeH. Cluster C-3 was the most reactive with PhSH and PhSeH but this complex was inactive in antimicrobial cytotoxicity testing. Cluster C-4 was not reactive with PhSH or PhSeH and it was completely inactive in cytotoxicity testing. Additional experiments are proposed as future work to better understand the complex interplay of steric and electronic effects in the [MoS4(AuL)2] clusters.

Download

Files over 10MB may be slow to open. For best results, right-click and select "save as..."

Share