The activated cluster Os3(CO)10(CH3CN)2 (1) reacts readily with a number of carboxylated chalcones and benzaldehydes (2a−j) to afford products with the general formula Os3(CO)10(µ-H)(µ-O2CR) (3a–j). The structures of all the novel clusters have been characterized by IR and 1H NMR spectroscopy, as well as mass spectrometry and elemental analysis. Single-crystal X-ray diffraction analysis has also been carried out for one of the carboxylated chalcones and two of the derivatized clusters. The activity of some of the derivatized clusters against the ER+ breast carcinoma MCF-7 cancer cell line has also been evaluated. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.