Issue 37, 2021

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

Abstract

We report the synthesis of the organo-osmium anticancer complex [Os(η6-p-cym)(N,N-azpy-NMe2)Br]PF6 (1) containing natural abundance 187Os (1.96%), and isotopically-enriched (98%) [187Os]-1. Complex 1 and [187Os]-1 contain a π-bonded para-cymene (p-cym), a chelated 4-(2-pyridylazo)-N,N-dimethylaniline (azpy-NMe2), 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 (IC50 = 0.40 μM). Complex [187Os]-1 was analysed by high-resolution ESI-MS, 1D 1H and 13C NMR, and 2D 1H COSY, 13C–1H HMQC, and 1H–187Os HMBC NMR spectroscopy. Couplings of 1H and 13C nuclei from the azpy/p-cym ligands to 187Os were observed with J-couplings (1J to 4J) ranging between 0.6–8.0 Hz. The 187Os chemical shift of [187Os]-1 (−4671.3 ppm, determined by 2D 1H–187Os HMBC NMR) is discussed in relation to the range of values reported for related Os(II) arene and cyclopentadienyl complexes (−2000 to −5200 ppm).

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

Supplementary files

Article information

Article type
Paper
Submitted
03 Jūl. 2021
Accepted
07 Aug. 2021
First published
24 Aug. 2021
This article is Open Access
Creative Commons BY license

Dalton Trans., 2021,50, 12970-12981

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

R. J. Needham, I. Prokes, A. Habtemariam, I. Romero-Canelón, G. J. Clarkson and P. J. Sadler, Dalton Trans., 2021, 50, 12970 DOI: 10.1039/D1DT02213J

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