Premium
Differential Anticancer Activities of the Geometric Isomers of Dinuclear Iridium(III) Complexes
Author(s) -
Pandrala Mallesh,
Sundaraneedi Madhu K.,
Ammit Alaina J.,
Woodward Clifford E.,
Wallace Lynne,
Keene F. Richard,
Collins J. Grant
Publication year - 2015
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.201501069
Subject(s) - chemistry , cis–trans isomerism , stereochemistry , iridium , nuclear magnetic resonance spectroscopy , dna , medicinal chemistry , biochemistry , catalysis
Abstract The anticancer activities of dinuclear iridium(III) complexes [{Ir(tpy)Cl} 2 {μ‐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 μ M ), it was relatively inactive against the nonmetastatic MCF‐7 line (29 μ M ). The three geometric isomers of Cl‐Irbb 16 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 (IC 50 = 2 μ 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 μ M , respectively). From log P measurements, the t,t isomer of Cl‐Irbb 16 (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.