Self-Assembly of Ambidentate Pyridyl-Carboxylate Ligands with Octahedral Ruthenium Metal Centers: Self-Selection for a Single-Linkage Isomer and Anticancer-Potency Studies

Abstract

The synthesis of six new [2+2] metallarectangles through the coordination-driven self-assembly of octahedral RuII-based acceptors with ambidentate pyridyl-carboxylate donors is described. These molecular rectangles are fully characterized by 1HNMR spectroscopy, high-resolution electrospray mass spectrometry, and single-crystal X-ray diffraction. In each case, despite the possible formation of multiple isomers, based on the relative orientation of the pyridyl and carboxylate groups (head-to-head versus head-to-tail), evidence for the formation of a single preferred ensemble (head-to-tail) was found in the 1HNMR spectra. Furthermore, the cytotoxicities of all of the rectangles were established against A549 (lung), AGS (gastric), HCT-15 (colon), and SK hep 1 (liver) human cancer cell lines. The cytotoxicities of rectangles that contained the 5,8-dihydroxy-1,4-naphthaquinonato bridging moiety between the Ru centers (911) were particularly high against AGS cancer cells, with IC50 values that were comparable to that of reference drug cisplatin.