Differential anticancer activities of the geometric isomers of dinuclear iridium(III) complexes

Pandrala, Mallesh, Sundaraneedi, Madhu K., Ammit, Alaina J., Woodward, Clifford E., Wallace, Lynne, Keene, F. Richard, and Collins, J. Grant (2015) Differential anticancer activities of the geometric isomers of dinuclear iridium(III) complexes. European Journal of Inorganic Chemistry, 2015 (34). pp. 5694-5701.

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Abstract

The anticancer activities of dinuclear iridium(III) complexes [{Ir(tpy)Cl}2{μ-bbn}]4+ {Cl-Irbbn; tpy = 2,2':6',2"-terpyridine, bbn = bis[4(4'-methyl-2,2'-bipyridyl)]-1,n-alkane (n = 7, 12 and 16)} against MCF-7 and MDA-MB-231 breast cancer cell lines have been determined. The activities of the Cl-Irbbn complexes increased with increasing chain length, the Cl-Irbb16 complex showing the best anticancer properties. However, while Cl-Irbb16 was active against the metastatic MDA-MB-231 cells (3 μM), it was relatively inactive against the nonmetastatic MCF-7 line (29 μM). The three geometric isomers of Cl-Irbb16 were isolated and characterised by NMR spectroscopy and mass spectrometry, and their anticancer activities, lipophilicities (log P) and DNA-binding abilities were examined. The trans,trans (t,t) isomer (IC50 = 2 μM against MDA-MB-231) showed considerably greater anticancer activity than the cis,trans (c,t) and cis,cis (c,c) isomers (8 and 31 μM, respectively). From log P measurements, the t,t isomer of Cl-Irbb16 (log P = –0.62) was found to be slightly more lipophilic than the other geometric isomers (–0.95 and –0.98 for the c,c and c,t isomers, respectively). Calf-thymus (CT) DNA-binding experiments demonstrated that the t,t isomer did induce a different alteration to the helix conformation compared to the other isomers. The results of this study also highlight the significance of the differences in three-dimensional shape that can be obtained through geometric isomerism for octahedral coordination complexes.

Item ID: 41416
Item Type: Article (Research - C1)
ISSN: 1099-0682
Keywords: iridium; dinuclear complexes; anticancer activity; isomers; structure–activity relationships; stereochemistry
Funders: University of New South Wales, Canberra
Date Deposited: 26 Nov 2015 03:37
FoR Codes: 03 CHEMICAL SCIENCES > 0302 Inorganic Chemistry > 030201 Bioinorganic Chemistry @ 30%
11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110899 Medical Microbiology not elsewhere classified @ 30%
03 CHEMICAL SCIENCES > 0302 Inorganic Chemistry > 030207 Transition Metal Chemistry @ 40%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 70%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 30%
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