Osmium(II)--versus ruthenium(II)--arene carbohydrate-based anticancer compounds: similarities and differences

The synthesis and in vitro anticancer activity of Os(II)-arene complexes with carbohydrate-derived phosphite co-ligands are reported. The compounds were characterized by standard methods and the molecular structure of dichlorido(eta(6)-p-cymene)(3,5,6-bicyclophosphite-1,2-O-isopropylidene-alpha-D-glucofuranoside)osmium(II) was determined by X-ray diffraction analysis. Complexes with chlorido leaving groups undergo hydrolysis by consecutive formation of aqua compounds, followed by cleavage of a P-O bond of sugar phosphite ligands, as demonstrated by NMR studies. These observations are similar to those of analogous Ru(II)-arene complexes; however the rate of hydrolysis is very slow for osmium compounds. The complexes with oxalato leaving groups resist hydrolysis; no hydrolytic species were detected by (31)P{(1)H} NMR spectroscopy over several days. Within this series of Os compounds, in vitro anticancer activity is highest for the most lipophilic chlorido complex dichlorido(eta(6)-p-cymene)(3,5,6-bicyclophosphite-1,2-O-cyclohexylidene-alpha-D-glucofuranoside)osmium(II).