Issue 12, 2017

Mitochondria-targeted spin-labelled luminescent iridium anticancer complexes


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.

Graphical abstract: Mitochondria-targeted spin-labelled luminescent iridium anticancer complexes

Supplementary files

Article information

Article type
Edge Article
23 Jul 2017
11 Oct 2017
First published
20 Oct 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 8271-8278

Mitochondria-targeted spin-labelled luminescent iridium anticancer complexes

V. Venkatesh, R. Berrocal-Martin, C. J. Wedge, I. Romero-Canelón, C. Sanchez-Cano, J. Song, J. P. C. Coverdale, P. Zhang, G. J. Clarkson, A. Habtemariam, S. W. Magennis, R. J. Deeth and P. J. Sadler, Chem. Sci., 2017, 8, 8271 DOI: 10.1039/C7SC03216A

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