Curran, DanielleDanielleCurran2022-05-052022-05-052021 the A2021http://hdl.handle.net/10197/12851We present herein, a series of N-heterocyclic carbene gold(I) complexes derived from (1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene)gold(I) chloride. Ligand substitution of this NHC-gold(I) chloride complex allowed the coordination of a variety of ligands to the gold(I) centre. These complexes were designed to create a structure-activity-relationship for NHC-gold(I) complexes. Chapter 1 introduces N-heterocyclic carbenes and highlights the importance of metal-based drug design. Chapter 2 describes the synthesis of NHC-gold(I) complexes with halide, carbene and phosphine ligands. In vitro MTT-based proliferation assays against the human colon carcinoma HCT-116 and the multidrug-resistant breast cancer cell line MCF-7 show the effect that ligand modification has on the antiproliferative properties of these gold(I) complexes. We found the cationic gold(I) complexes to be promising anticancer drug candidates. Chapter 3 discusses NHC-gold(I) acetylides which did not exhibit great cytotoxicity but presented interesting aurophilic interactions in the solid state. Chapter 4 presents optimised NHC-gold(I) complexes with the introduction of dithiocarbamate ligands. In vitro cell tests reported the highest activity observed with an IC50 value of 0.28 µM against the breast cancer cell line MCF-7. An in vivo xenograft mouse model experiment was carried out with the dimethyldithiocarbamate complex against the human prostate cancer PC-3 which showed the NHC-gold(I) complex had a strong chemotherapeutic properties. Chapter 5 describes the synthesis of NHC-gold(I) cysteine derivatives. Solid-phase peptide synthesis is used to prepare a series of cysteine-based dipeptides which were coordinated to the NHC-gold(I) complex.enGoldN-Heterocyclic CarbeneAnticancerDoctoral Thesis2021-12-08https://creativecommons.org/licenses/by-nc-nd/3.0/ie/