The synthesis, characterisation, and biological properties of tetradentate ligands and their ruthenium(ii) complexes

Abstract

Cancer continues to be an ongoing global health concern placing a considerable burden on the health system. Similarly, antibiotic resistant microbial infections are increasing with projections for both illnesses becoming the leading cause of death worldwide. The outstanding success of platinum-based chemotherapeutics such as cisplatin and the promising results of ruthenium anticancer drugs such as NAMI-A and KP1019, supports further investigation into transition metals as anticancer drugs. However, problems that are associated with platinum-based drugs include toxicity, resistance, selectivity, or limitations concerning the degree of activity. This has prompted investigation into optimisation strategies based on different transition metals and ligands. While the metal complexes previously investigated for biological activity have demonstrated anticancer activity, synthetic advances have also contributed to the development of antibacterial activity. Ruthenium(II) based complexes are of particular interest, as they are versatile, stable and commonly bio-active, suggesting that further research in this field would be advantageous. Ligands play a significant role in coordination chemistry, both independently and when coordinated to transition metals. The study of multidentate ligands, has contributed profoundly to the understanding of coordinated structures, the development of compounds displaying biological activity, and their influence on compound stereochemistry. The research presented in this thesis focuses on synthetic techniques to expand the utility of N4-tetradentate ligands (N4-TLs); it includes the synthesis of N4-TLs, the coordination of N4-TLs and bidentate ligands to ruthenium(II), and the assessment of their biological activity against cancer and bacterial cells. A series of N4-TLs (1 "" 33) with the general name N,Nʹ-bis(2-pyridylmethyl)-1,2-diaminoethane (picen, N4-TL-1) and its analogues with varying length of achiral and chiral diamine chains and their methylated nitrogens have been synthesised. The N4-TLs were successfully synthesised and characterised. All structures were confirmed using NMR, ESI-MS, HPLC, UV-Vis and where appropriate CD spectroscopy. Throughout this thesis several N4-TLs together with their respective ruthenium(II) complexes were successfully synthesised and characterised in detail. The N4-TLs and ruthenium(II) complexes also revealed varying levels of anticancer and antimicrobial properties.

Date of Award	2020
Original language	English