Synthesis and anticancer activity of ruthenium half-sandwich complexes comprising combined metal centrochirality and planar chirality

Reported herein is the synthesis and evaluation of anticancer properties of a well-established organometallic protein kinase inhibitor scaffold in which the stereochemical complexity is increased. The investigated ruthenium eta(5)-cyclopentadienyl half-sandwich complexes contain a bidentate pyridocarbazole and a monodentate CO ligand, thereby leading to four different stereoisomers due to the combined presence of ruthenium-centered chirality and planar chirality of the pi -coordinated trisubstituted cyclopentadienyl moiety (two diastereomers as mixtures of enantiomers). While one of the two racemic diastereomers turns out to be nontoxic towards cancer cells, the second racemic diastereomer displays high cytotoxicities towards different cancer cell lines in vitro, thus demonstrating the intertwining of organometallic stereochemistry and biological activity. (C) 2014 Elsevier B.V. All rights reserved.