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

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    Publication date
    2016-09-07
    Author
    Lord, Rianne M.
    Allison, Simon J.
    Rafferty, K.
    Ghandhi, L.
    Pask, C.M.
    McGowan, P.C.
    Keyword
    p-cymene ruthenium quinaldamide complexes; Hydrogen bridged; Chemotherapy; Anti-cancer agents
    Rights
    © 2016 RSC. Reproduced with permission from the publisher in accordance with the publisher's self-archiving policy.
    Peer-Reviewed
    yes
    
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    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 cisplatinresistant 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
    URI
    http://hdl.handle.net/10454/9487
    Version
    Accepted manuscript
    Citation
    Lord RM, Allison SJ, Rafferty K, Ghandi L, Pask CM and McGowan PC (2016) Cytotoxic hydrogen bridged ruthenium quinaldamide complexes showing induced cancer cell death by apoptosis. Dalton Transactions. 45: 13196-13203.
    Link to publisher’s version
    http://dx.doi.org/10.1039/c6dt01464j
    Type
    Article
    Collections
    Life Sciences Publications

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