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Issue 8, 2012
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The contrasting chemical reactivity of potent isoelectronic iminopyridine and azopyridine osmium(II) arene anticancer complexes

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Abstract

A wide variety of steric and electronic features can be incorporated into transition metal coordination complexes, offering the prospect of rationally-designed therapeutic agents with novel mechanisms of action. Here we compare the chemical reactivity and anticancer activity of organometallic OsII complexes [Os(η6-arene)(XY)Z]PF6 where arene = p-cymene or biphenyl, XY = N,N′-chelated phenyliminopyridine or phenylazopyridine derivatives, and Z = Cl or I. The X-ray crystal structure of [Os(η6-p-cym)(Impy-OH)I]PF6·0.5CH2Cl2·H2O (Impy-OH = 4-[(2-pyridinylmethylene)amino]-phenol) is reported. Like the azopyridine complexes we reported recently (Dalton Trans., 2011, 40, 10553–10562), some iminopyridine complexes are also potently active towards cancer cells (nanomolar IC50 values). However we show that, unlike the azopyridine complexes, the iminopyridine complexes can undergo aquation, bind to the nucleobase guanine, and oxidize coenzyme nicotine adenine dinucleotide (NADH). We report the first detection of an Os-hydride adduct in aqueous solution by 1H NMR (−4.2 ppm). Active iminopyridine complexes induced a dramatic increase in the levels of reactive oxygen species (ROS) in A549 lung cancer cells. The anticancer activity may therefore involve interference in the redox signalling pathways in cancer cells by a novel mechanism.

Graphical abstract: The contrasting chemical reactivity of potent isoelectronic iminopyridine and azopyridine osmium(ii) arene anticancer complexes

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Publication details

The article was received on 22 Feb 2012, accepted on 23 May 2012 and first published on 12 Jun 2012


Article type: Edge Article
DOI: 10.1039/C2SC20220D
Citation: Chem. Sci., 2012,3, 2485-2494
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    The contrasting chemical reactivity of potent isoelectronic iminopyridine and azopyridine osmium(II) arene anticancer complexes

    Y. Fu, M. J. Romero, A. Habtemariam, M. E. Snowden, L. Song, G. J. Clarkson, B. Qamar, A. M. Pizarro, P. R. Unwin and P. J. Sadler, Chem. Sci., 2012, 3, 2485
    DOI: 10.1039/C2SC20220D

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