NMR studies of group 8 metallodrugs: (187)Os-enriched organo-osmium half-sandwich anticancer complex

We report the synthesis of the organo-osmium anticancer complex [Os(η(6)-p-cym)(N,N-azpy-NMe(2))Br]PF(6) (1) containing natural abundance (187)Os (1.96%), and isotopically-enriched (98%) [(187)Os]-1. Complex 1 and [(187)Os]-1 contain a π-bonded para-cymene (p-cym), a chelated 4-(2-pyridylazo)-N,N-dimethylaniline (azpy-NMe(2)), and a monodentate bromide as ligands. The X-ray crystal structure of 1 confirmed its half-sandwich ‘piano-stool’ configuration. Complex 1 is a member of a family of potent anticancer complexes, and exhibits sub-micromolar activity against A2780 human ovarian cancer cells (IC(50) = 0.40 μM). Complex [(187)Os]-1 was analysed by high-resolution ESI-MS, 1D (1)H and (13)C NMR, and 2D (1)H COSY, (13)C–(1)H HMQC, and (1)H–(187)Os HMBC NMR spectroscopy. Couplings of (1)H and (13)C nuclei from the azpy/p-cym ligands to (187)Os were observed with J-couplings ((1)J to (4)J) ranging between 0.6–8.0 Hz. The (187)Os chemical shift of [(187)Os]-1 (−4671.3 ppm, determined by 2D (1)H–(187)Os HMBC NMR) is discussed in relation to the range of values reported for related Os(ii) arene and cyclopentadienyl complexes (−2000 to −5200 ppm).