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Title: Ruthenium(II) cis-triaminocyclohexane complexes as anti-cancer compounds
Author: Gamble, Aimee J.
ISNI:       0000 0004 2723 2178
Awarding Body: University of York
Current Institution: University of York
Date of Award: 2012
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Ruthenium complexes are promising candidates for the treatment of cancers. Two ruthenium(III) complexes have previously completed phase I clinical trials and half-sandwich ruthenium(II) η6-arene complexes are receiving much interest as anti-cancer agents. A range of new ruthenium(II) complexes have been prepared with a κ3-N fac-coordinating six electron donor, cis-1,3,5-triaminocyclohexane (cis-tach), replacing the η6-arene ligand. It is hypothesised that the cis-tach ligand will allow highly active complexes with good water solubility. Initial access to ruthenium(II) cis-tach complexes was established with triphenylphosphane ligands, yielding the complexes [RuCl(cis-tach)(PPh3)2]Cl and [RuCl2(cis-tach)(PPh3)]. The complexes adopt a piano-stool type structure, similar to η6-arene complexes. Use of labile dmso ligands in [RuCl(dmso-S)2(cis-tach)]Cl permitted the preparation of a range of complexes. Those with N–N and P–P bidentate chelating ligands, following the formula [Ru(dmso-S)(N–N)(cis-tach)]2+ and [RuCl(P–P)(cis-tach)]+ were studied. Complexes with N–N chelating ligands were found to be inert to substitution in aqueous solution compared to the bis-dmso complex, and were inactive in tumour growth inhibition. The complexes with chelating diphosphane ligands are highly water-soluble, with excellent in vitro activity in the inhibition of tumor cell growth; two of which were found to exceed that of cisplatin. A structure-activity relationship is discussed, and two compounds were selected for further study for their good water solubility and high activity respectively. The aqueous chemistry and the interaction of two of these complexes with small models of biomolecules and DNA was also investigated.
Supervisor: Lynam, Jason M. ; Walton, Paul H. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available