Osmium Carbonyl Clusters Containing Labile Ligands Hyperstabilize Microtubules

Abstract

A study into the possible molecular targets of the osmium carbonyl cluster Os₃(CO)₁₀(NCCH₃)₂ (<b>2</b>) in the ER− breast carcinoma (MDA-MB-231) cell line was carried out. Infrared and ¹H NMR analyses of cells treated with <b>2</b> showed the formation of carboxylato- and thiolato-bridged clusters from the interaction with intracellular carboxylic acid and sulfhydryl residues. The cytotoxicity of <b>2</b> was reduced in the presence of fetal bovine serum, and measurement with Ellman’s reagent as well as fluorescence confocal microscopy with tetramethylrhodamine-5-maleimide staining all demonstrated binding to intracellular sulfhydryl groups leading up to cell disruption. Tubulin-FITC antibody staining of treated cells showed disruption of the microtubules, and a tubulin polmerization assay showed that <b>2</b> induced hyperstabilization of the microtubules.