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Half‐sandwich ruthenium, rhodium and iridium complexes featuring oxime ligands: Structural studies and preliminary investigation of in vitro and in vivo anti‐tumour activities

Palepu, Narasinga Rao, Adhikari, Sanjay, Premkumar, Richard J, Verma, Akalesh K, Shepherd, Samantha L, Phillips, Roger M, Kaminsky, Werner and Kollipara, Mohan Rao (2016) Half‐sandwich ruthenium, rhodium and iridium complexes featuring oxime ligands: Structural studies and preliminary investigation of in vitro and in vivo anti‐tumour activities. Applied Organometallic Chemistry. ISSN 0268-2605

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Abstract

Half‐sandwich ruthenium, rhodium and iridium complexes (1–12) were synthesised with aldoxime (L1), ketoxime (L2) and amidoxime (L3) ligands. Ligands have the general formula [PyC(R)NOH], where R = H (L1), R = CH3 (L2) and R = NH2 (L3). Reaction of [{(arene)MCl2}2] (arene = p‐cymene, benzene, Cp*; M = Ru, Rh, Ir) with ligands L1–L3 in 1:2 metal precursor‐to‐ligand ratio yielded complexes such as [{(arena)MLκ2(N∩N)Cl}]PF6. All the ligands act as bidentate chelating nitrogen donors in κ2 (N∩N) fashion while forming complexes. In vitro anti‐tumour activity of complexes 2 and 10 against HT‐29 (human colorectal cancer), BE (human colorectal cancer) and MIA PaCa‐2 (human pancreatic cancer) cell lines and non‐cancer cell line ARPE‐19 (human retinal epithelial cells) revealed a comparable activity although complex 2 demonstrated greater selectivity for MIA PaCa‐2 cells than cisplatin. Further studies demonstrated that complexes 3, 6, 9 and 12 induced significant apoptosis in Dalton's ascites lymphoma (DL) cells. In vivo anti‐tumour activity of complex 2 on DL‐bearing mice revealed a statistically significant anti tumour activity (P = 0.0052). Complexes 1–12 exhibit HOMO–LUMO energy gaps from 3.31 to 3.68 eV. Time‐dependent density functional theory calculations explain the nature of electronic transitions and were in good agreement with experiments.

Item Type: Article
Subjects: R Medicine > RM Therapeutics. Pharmacology
Schools: School of Applied Sciences
Related URLs:
Depositing User: Roger Phillips
Date Deposited: 08 Nov 2016 12:53
Last Modified: 23 Nov 2016 11:13
URI: http://eprints.hud.ac.uk/id/eprint/29834

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