Pyridylphosphinate Metal Complexes: Synthesis, Structural Characterisation and Biological Activity

Cross, J.M.; Gallagher, N.; Gill, J.H.; Jain, M.; McNeillis, A.W.; Rockley, K.L.; Tscherny, F.H.; Wirszycz, N.J.; Yufit, D.S.; Walton, J.W.

doi:10.1039/c6dt01264g

Pyridylphosphinate Metal Complexes: Synthesis, Structural Characterisation and Biological Activity

Cross, J.M.; Gallagher, N.; Gill, J.H.; Jain, M.; McNeillis, A.W.; Rockley, K.L.; Tscherny, F.H.; Wirszycz, N.J.; Yufit, D.S.; Walton, J.W.

Authors

J.M. Cross

N. Gallagher

J.H. Gill

M. Jain

A.W. McNeillis

K.L. Rockley

F.H. Tscherny

N.J. Wirszycz

Dr Dmitry Yufit d.s.yufit@durham.ac.uk
Academic Visitor

Dr James Walton james.walton@durham.ac.uk
Associate Professor

Abstract

For the first time, a series of 25 pseudo-octahedral pyridylphosphinate metal complexes (Ru, Os, Rh, Ir) has been synthesised and assessed in biological systems. Each metal complex incorporates a pyridylphosphinate ligand, a monodentate halide and a capping η6-bound aromatic ligand. Solid- and solution-state analyses of two complexes reveal a structural preference for one of a possible two diastereomers. The metal chlorides hydrolyse rapidly in D2O to form a 1:1 equilibrium ratio between the aqua and chloride adducts. The pKa of the aqua adduct depends upon the pyridyl substituent and the metal but has little dependence upon the phosphinate R’ group. Toxicity was measured in vitro against non-small cell lung carcinoma H460 cells, with the most potent complexes reporting IC50 values around 50 μM. Binding studies with selected amino acids and nucleobases provide a rationale for the variation in toxicity observed within the series. Finally, an investigation into the ability of the chelating amino acid L-His to displace the phosphinate O‒metal bond shows the potential for phosphinate complexes to act as prodrugs that can be activated in the intracellular environment.

Citation

Cross, J., Gallagher, N., Gill, J., Jain, M., McNeillis, A., Rockley, K., …Walton, J. (2016). Pyridylphosphinate Metal Complexes: Synthesis, Structural Characterisation and Biological Activity. Dalton Transactions, 45(32), 12807-12813. https://doi.org/10.1039/c6dt01264g

Journal Article Type	Article
Acceptance Date	Jul 9, 2016
Online Publication Date	Jul 11, 2016
Publication Date	Aug 28, 2016
Deposit Date	Jul 11, 2016
Publicly Available Date	Jul 9, 2017
Journal	Dalton Transactions
Print ISSN	1477-9226
Electronic ISSN	1477-9234
Publisher	Royal Society of Chemistry
Peer Reviewed	Peer Reviewed
Volume	45
Issue	32
Pages	12807-12813
DOI	https://doi.org/10.1039/c6dt01264g