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The contrasting chemical reactivity of potent isoelectronic iminopyridine and azopyridine osmium(ii) arene anticancer complexes
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Fu, Y. (Ying), Romero, Maria, Habtemariam, Abraha, Snowden, Michael E., Song, Lijiang, Clarkson, Guy J., Qamar, Bushra, Pizarro, Ana M., Unwin, Patrick R. and Sadler, P. J. (2012) The contrasting chemical reactivity of potent isoelectronic iminopyridine and azopyridine osmium(ii) arene anticancer complexes. Chemical Science, Vol.3 (No.8). pp. 2485-2494. doi:10.1039/c2sc20220d ISSN 2041-6520.
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WRAP_Romero_489_Chem Sci 2012_3_2485_Maria J Romero_deposit.pdf - Accepted Version Download (1151Kb) | Preview |
Official URL: http://dx.doi.org/10.1039/C2SC20220D
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.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QD Chemistry | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||
Library of Congress Subject Headings (LCSH): | Antineoplastic agents, Osmium -- Therapeutic use, Aromatic compounds -- Therapeutic use, Transition metal complexes -- Therapeutic use | ||||
Journal or Publication Title: | Chemical Science | ||||
Publisher: | Royal Society of Chemistry | ||||
ISSN: | 2041-6520 | ||||
Official Date: | 2012 | ||||
Dates: |
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Volume: | Vol.3 | ||||
Number: | No.8 | ||||
Page Range: | pp. 2485-2494 | ||||
DOI: | 10.1039/c2sc20220d | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access | ||||
Date of first compliant deposit: | 24 December 2015 | ||||
Date of first compliant Open Access: | 24 December 2015 | ||||
Funder: | European Research Council (ERC), Engineering and Physical Sciences Research Council (EPSRC), European Regional Development Fund (ERDF), Advantage West Midlands (AWM) | ||||
Grant number: | 247450 (ERC) |
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