Substitution Inert Platinum (II) Complexes and Their Non-covalent Interactions with Proteins
Author | : Thomas A. Wells |
Publisher | : |
Total Pages | : |
Release | : 2020 |
Genre | : Chemotherapy |
ISBN | : |
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Traditional platinum complexes are commonplace in chemotherapeutics. While effective, the toxicity of these complexes and development of resistance are inherent drawbacks that need to be addressed. This work focuses on the development of a new class of platinum (II) complexes designed for non-covalent, electrostatic interactions with proteins relevant to cancer and HIV-1. Chapter two focuses on mono and dinuclear substitution-inert platinum complexes and their selectivity for the N-terminal of the HIV-1 NCp7 protein. Chapters three and four investigate a second phenotype of mononuclear platinum complexes with bis conformations and their interactions with the p53-MDM2 interface. Chapter five provides insight into isoelectronic gold (III) complexes and an aryl-transfer mechanism to NCp7. Chapter six explains the recovery of platinum from laboratory wastes. Overall, the work presented in this dissertation expands on the class of substitution-inert platinum(II) complexes and assesses their viability to interact with specific active-site residues of the HIV-1 NCp7 protein and the p53-MDM2 interface.