Cytotoxic hydrogen bridged ruthenium quinaldamide complexes showing induced cancer cell death by apoptosis

Rianne M. Lord; Simon J. Allison; Karen Rafferty; Laura Ghandhi; Christopher M. Pask; Patrick C. McGowan

doi:10.1039/c6dt01464j

Cytotoxic hydrogen bridged ruthenium quinaldamide complexes showing induced cancer cell death by apoptosis

Rianne M. Lord, Simon J. Allison, Karen Rafferty, Laura Ghandhi, Christopher M. Pask, Patrick C. McGowan

University of Leeds

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

This report presents the first known p-cymene ruthenium quinaldamide complexes which are stabilised by a hydrogen-bridging atom, [{(p-cym)Ru^IIX(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 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. 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.

Original language	English
Pages (from-to)	13196-13203
Number of pages	8
Journal	Dalton Transactions
Volume	45
Issue number	33
Early online date	4 Jul 2016
DOIs	https://doi.org/10.1039/c6dt01464j
Publication status	Published - 7 Sept 2016

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title = "Cytotoxic hydrogen bridged ruthenium quinaldamide complexes showing 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)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(μ-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. X-ray crystallographic analysis is presented for six new structures with O⋯O distances of 2.420(4)-2.448(15) {\AA}, 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.",

author = "Lord, \{Rianne M.\} and Allison, \{Simon J.\} and Karen Rafferty and Laura Ghandhi and Pask, \{Christopher M.\} and McGowan, \{Patrick C.\}",

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T1 - Cytotoxic hydrogen bridged ruthenium quinaldamide complexes showing induced cancer cell death by apoptosis

AU - Lord, Rianne M.

AU - Allison, Simon J.

AU - Rafferty, Karen

AU - Ghandhi, Laura

AU - Pask, Christopher M.

AU - McGowan, Patrick C.

PY - 2016/9/7

Y1 - 2016/9/7

N2 - This report presents the first known p-cymene ruthenium quinaldamide complexes which are stabilised by a hydrogen-bridging 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(μ-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. 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.

AB - This report presents the first known p-cymene ruthenium quinaldamide complexes which are stabilised by a hydrogen-bridging 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(μ-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. 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.

UR - https://www.scopus.com/pages/publications/84983348582

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DO - 10.1039/c6dt01464j

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EP - 13203

JO - Dalton Transactions

JF - Dalton Transactions

IS - 33

ER -

Cytotoxic hydrogen bridged ruthenium quinaldamide complexes showing induced cancer cell death by apoptosis

Abstract

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