Cytotoxic hydrogen bridged ruthenium quinaldamide complexes showing induced cancer cell death by apoptosis. Issue 33 (15th July 2016)

• Record Type: Journal Article
• Authors: Lord, Rianne M.; Allison, Simon J.; Rafferty, Karen; Ghandhi, Laura; Pask, Christopher M.; McGowan, Patrick C.
• Is Part Of: Dalton transactions. Volume 45:Issue 33(2016)
• Page Start: 13196
• Page End: 13203
• Publication Date: 2016-07-15
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/c6dt01464j
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : This report presents the first known p -cymene ruthenium quinaldamide complexes stabilised by a hydrogen-bridging atom, which are cytotoxic and show induced cancer cell death by apoptosis. Abstract : This report presents the first known p -cymene ruthenium quinaldamide complexes which are stabilised by a hydrogen-bridging atom, [{( p -cym)Ru II X( N, N )}{H + }{( N, N )XRu II ( p -cym)}][PF6 ] ( N, N = functionalised quinaldamide and X = Cl or Br). These complexes are formed by a reaction of [ p -cymRu(μ-X)2 ]2 with a functionalised quinaldamide ligand. When filtered over NH4 PF6, and under aerobic conditions the equilibrium of NH4 PF6 ⇔ 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. X-ray crystallographic analysis is presented for six new structures with O⋯O distances of 2.420(4)–2.448(15) 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.