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

作者：Pandrala Mallesh; Sundaraneedi Madhu K; Ammit Alaina J; Woodward Clifford E; Wallace Lynne^*; Keene F Richard; Collins J Grant

来源：European Journal of Inorganic Chemistry, 2015, 2015(34): 5694-5701.

DOI：10.1002/ejic.201501069

• Iridium
• Dinuclear complexes
• Anticancer activity
• Isomers
• Structure-activity relationships
• Stereochemistry

The anticancer activities of dinuclear iridium(III) complexes [{Ir(tpy)Cl}(2){mu-bb(n)}](4+) {Cl-Irbb(n); tpy = 2,2 ':6 ',2 ''-terpyridine, bb(n) = 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-Irbb(n) complexes increased with increasing chain length, the Cl-Irbb(16) complex showing the best anticancer properties. However, while Cl-Irbb(16) was active against the metastatic MDA-MB-231 cells (3 mu M), it was relatively inactive against the nonmetastatic MCF-7 line (29 mu M). The three geometric isomers of Cl-Irbb(16) were isolated and characterised by NMR spectroscopy and mass spectrometry, and their anticancer activities, lipophilicities (logP) and DNA-binding abilities were examined. The trans, trans (t,t) isomer (IC50 = 2 mu M against MDA-MB-231) showed considerably greater anticancer activity than the cis, trans (c,t) and cis, cis (c, c) isomers (8 and 31 mu M, respectively). From logP measurements, the t, t isomer of Cl-Irbb(16) (logP = -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 high-light the significance of the differences in three-dimensional shape that can be obtained through geometric isomerism for octahedral coordination complexes.

• 出版日期2015-12