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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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) 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 languageEnglish
Pages (from-to)13196-13203
Number of pages8
JournalDalton Transactions
Volume45
Issue number33
Early online date4 Jul 2016
DOIs
Publication statusPublished - 2016

Fingerprint

Ruthenium
Cell death
Hydrogen
Cells
Apoptosis
Ligands
Bromides
Chlorides
Cisplatin
Hydrogen bonds
Stabilization
X rays
Atoms

Cite this

Lord, Rianne M. ; Allison, Simon J. ; Rafferty, Karen ; Ghandhi, Laura ; Pask, Christopher M. ; McGowan, Patrick C. / Cytotoxic hydrogen bridged ruthenium quinaldamide complexes showing induced cancer cell death by apoptosis. In: Dalton Transactions. 2016 ; Vol. 45, No. 33. pp. 13196-13203.
@article{a8a8b9d5fd0443aab4077c0539b5a908,
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.}",
year = "2016",
doi = "10.1039/c6dt01464j",
language = "English",
volume = "45",
pages = "13196--13203",
journal = "Dalton Transactions",
issn = "1477-9226",
publisher = "Royal Society of Chemistry",
number = "33",

}

Cytotoxic hydrogen bridged ruthenium quinaldamide complexes showing induced cancer cell death by apoptosis. / Lord, Rianne M.; Allison, Simon J.; Rafferty, Karen; Ghandhi, Laura; Pask, Christopher M.; McGowan, Patrick C.

In: Dalton Transactions, Vol. 45, No. 33, 2016, p. 13196-13203.

Research output: Contribution to journalArticle

TY - JOUR

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

Y1 - 2016

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 - http://www.scopus.com/inward/record.url?scp=84983348582&partnerID=8YFLogxK

U2 - 10.1039/c6dt01464j

DO - 10.1039/c6dt01464j

M3 - Article

VL - 45

SP - 13196

EP - 13203

JO - Dalton Transactions

JF - Dalton Transactions

SN - 1477-9226

IS - 33

ER -