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Cytotoxic Hydrogen Bridged Ruthenium Quinaldamide Complexes Showing Induced Cancer Cell Death by Apoptosis

Lord, Rianne Michaela, Allison, Simon J., Rafferty, Karen, Ghandhi, Laura, Pask, Christopher M. and McGowan, Patrick C. (2016) Cytotoxic Hydrogen Bridged Ruthenium Quinaldamide Complexes Showing Induced Cancer Cell Death by Apoptosis. Dalton Trans.. ISSN 1477-9226

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Abstract

This report presents the first known p-cymene ruthenium quinaldamide complexes which are stablized by a hydrogenbridging atom, [[{(p-cym)RuIIX(N,N)}{H+ }{(N,N)XRuII(p-cym)}][PF6] (N,N = functionalised quinaldamide and X = Cl or Br).
These complexes are formed by a reaction of [p-cymRu(-X)2]2 with a functionalised quinaldamide ligand. When filtered over NH4PF6, and under aerobic conditions the equilibrium of NH4PF6  NH3 + HPF6 enables incorporation of HPF6 and the stabilisation of two monomeric ruthenium complexes by a bridging H+
, which are counter-balanced by a PF6 counterion. Xray crystallographic analysis is presented for six new structures with O···O distances of 2.430(3)-2.444(17) Å, which is significant for strong hydrogen bonds. Chemosensitivity studies against HCT116, A2780 and cisplatin-resistant A2780cis human cancer cells showed the ruthenium complexes with a bromide ancillary ligand to be more potent than those with a chloride ligand. The 4'-fluoro compounds show a reduction in potency for both chloride and bromide complexes against all cell lines, but an increase in selectivity towards cancer cells compared to non-cancer ARPE-19 cells, with a selectivity index > 1. Mechanistic studies showed a clear correlation between IC50 values and induction of cell death by apoptosis.

Item Type: Article
Subjects: Q Science > QD Chemistry
Schools: School of Applied Sciences
Related URLs:
Depositing User: Elizabeth Boulton
Date Deposited: 12 Jul 2016 10:59
Last Modified: 13 Nov 2016 15:16
URI: http://eprints.hud.ac.uk/id/eprint/28983

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