Taotao Zou Libri

The thesis explores innovative gold- and platinum-based anti-cancer agents that operate through unique mechanisms distinct from cisplatin. It emphasizes the use of N-heterocyclic carbene (NHC) ligands, enhancing the stability and reactivity of metal complexes. Key findings include Au(III) complexes that serve as both fluorescent probes and anti-cancer agents, a dinuclear gold(I) complex that effectively inhibits tumor growth in mice without side effects, and luminescent platinum(II) complexes that target the endoplasmic reticulum, inducing cell apoptosis. The research underscores the clinical promise of these metal complexes in cancer therapy.

This thesis focuses on the development of gold- and non-classical platinum-based anti-cancer agents that display distinctively different anti-cancer mechanisms compared to the commonly used cisplatin. These metal complexes contain N-heterocyclic carbene (NHC) ligands which are able to form strong M-C(NHC) bonds, conferring high stability and favorable lipophilicity, reactivity and binding specificity of metal complexes on biomolecules. The author demonstrates significant advances made in anti-cancer gold(III), gold(I) and platinum(II) complexes. Detailed chemical synthesis, in vitro and/or in vivo anti-cancer activities are clearly presented including: (i) a class of Au(III) complexes containing a highly fluorescent N^N^N ligand and NHC ligand that simultaneously act as fluorescent thiol “switch-on” probes and anti-cancer agents; (ii) a dinuclear gold(I) complex with a mixed diphosphine and bis(NHC) ligand displaying favorable stability and showing significant inhibition of tumor growth in two independent mice models with no observable side effects; and (iii) a panel of stable luminescent cyclometalated platinum(II) complexes exhibiting high specificity to localize to the endoplasmic reticulum (ER) domain, inducing ER stress and cell apoptosis. These works highlight the clinical potential that gold and platinum complexes offer for cancer treatment.