From hydrolytically labile to hydrolytically stable Ru(II)-arene anticancer complexes with carbohydrate-derived co-ligands

The synthesis, characterization, reactivity and in vitro anticancer activity of a series of Ru-II-arene complexes with carbohydrate-derived phosphite and biscarboxylato co-ligands are reported. The compounds were characterized by NMR spectroscopy and electrospray ionization (ESI) mass spectrometry, and the molecular structures of oxalato(eta(6)-p-cymene)(3,5,6-bicyclophosphite-1,2-O-isopropylidene-alpha-D-glucofuranoside)ruthenium(II) and oxalato(eta(6)-p-cymene)(3,5,6-bicyclophosphite-1,2-O-cyclohexylidene-alpha-D-glucofuranoside)ruthenium(II) were determined by X-ray diffraction analysis. In contrast to their dichlorido counterparts, the biscarboxylato complexes did not exhibit significant reactivity towards biomolecules, such as cysteine, methionine, ubiquitin or the DNA model 5'-GMP, and resist hydrolysis; no hydrolytic species were detected by H-1 and P-31(H-1) NMR spectroscopy over several days. These structural alterations led to a decrease in the tumor-inhibiting potency of the compounds in human cancer cell lines. (C) 2010 Elsevier Inc. All rights reserved.