Mitochondria-targeted spin-labelled luminescent iridium anticancer complexes

Venkatesh, V. et al. (2017) Mitochondria-targeted spin-labelled luminescent iridium anticancer complexes. Chemical Science, 8(12), pp. 8271-8278. (doi: 10.1039/C7SC03216A)

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Mitochondria generate energy but malfunction in many cancer cells, hence targeting mitochondrial metabolism is a promising approach for cancer therapy. Here we have designed cyclometallated iridium(III) complexes, containing one TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) spin label [C43H43N6O2Ir1·PF6]˙ (Ir-TEMPO1) and two TEMPO spin labels [C52H58N8O4Ir1·PF6]˙ (Ir-TEMPO2). Electron paramagnetic resonance (EPR) spectroscopy revealed spin–spin interactions between the TEMPO units in Ir-TEMPO2. Both Ir-TEMPO1 and Ir-TEMPO2 showed bright luminescence with long lifetimes (ca. 35–160 ns); while Ir-TEMPO1 displayed monoexponential decay kinetics, the biexponential decays measured for Ir-TEMPO2 indicated the presence of more than one energetically-accessible conformation. This observation was further supported by density functional theory (DFT) calculations. The antiproliferative activity of Ir-TEMPO2 towards a range of cancer cells was much greater than that of Ir-TEMPO1, and also the antioxidant activity of Ir-TEMPO2 is much higher against A2780 ovarian cancer cells when compared with Ir-TEMPO1. Most notably Ir-TEMPO2 was particularly potent towards PC3 human prostate cancer cells (IC50 = 0.53 μM), being ca. 8× more active than the clinical drug cisplatin, and ca. 15× more selective towards cancer cells versus normal cells. Confocal microscopy showed that both Ir-TEMPO1 and Ir-TEMPO2 localise in the mitochondria of cancer cells.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Magennis, Dr Steven
Authors: Venkatesh, V., Berrocal-Martin, R., Wedge, C. J., Romero-Canelón, I., Sanchez-Cano, C., Song, J.-I., Coverdale, J. P.C., Zhang, P., Clarkson, G. J., Habtemariam, A., Magennis, S. W., Deeth, R. J., and Sadler, P. J.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Chemical Science
Publisher:Royal Society of Chemistry
ISSN (Online):2041-6539
Published Online:20 October 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Chemical Science 8(12):8271-8278
Publisher Policy:Reproduced under a Creative Commons License

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