NDLI: Mitochondria-targeted spin-labelled luminescent iridium anticancer complexes† †Electronic supplementary information (ESI) available. CCDC 1522104. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc03216a

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Mitochondria-targeted spin-labelled luminescent iridium anticancer complexes† †Electronic supplementary information (ESI) available. CCDC 1522104. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc03216a

Content Provider	Semantic Scholar
Author	Venkatesh, V. Berrocal-Martin, Raul Wedge, Christopher J. Romero-Canelón, Isolda Sanchez-Cano, Carlos Song, Ji-Inn Coverdale, James P. C. Zhang, Pingyu Clarkson, Guy J. Habtemariam, Abraha Magennis, Steven W. Deeth, Robert J. Sadler, Peter J.
Copyright Year	2017
Abstract	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.
Starting Page	8271
Ending Page	8278
Page Count	8
File Format	PDF HTM / HTML
DOI	10.1039/c7sc03216a
PubMed reference number	29568475
Journal	Medline
Volume Number	8
Alternate Webpage(s)	https://research.birmingham.ac.uk/portal/files/48557047/C7SC03216A.pdf
Alternate Webpage(s)	http://eprints.hud.ac.uk/id/eprint/34086/1/c7sc03216a.pdf
Alternate Webpage(s)	http://eprints.gla.ac.uk/150228/7/150228.pdf
Alternate Webpage(s)	http://wrap.warwick.ac.uk/100785/1/WRAP-mitochondria-targeted%20spin-labelled-luminescent-iridium-anticancer-complexes-Sadler-2017.pdf
Alternate Webpage(s)	https://doi.org/10.1039/c7sc03216a
Journal	Chemical science
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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