Differential Anticancer Activities of the Geometric Isomers of Dinuclear Iridium(III) Complexes

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.