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The OsII arene ethylenediamine (en) complexes (η6-biphenyl)Os(en)ClZ, Z = BPh4 (4) and BF4 (5), are inactive toward A2780 ovarian cancer cells despite 4 being isostructural with an active RuII analogue, 4R. Hydrolysis of 5 occurred 40 times more slowly than 4R. The aqua adduct 5A has a low pKa (6.3) compared to that of (η6-biphenyl)Ru(en)(OH2)2+ (7.7) and is therefore largely in the hydroxo form at physiological pH. The rate and extent of reaction of 5 with 9-ethylguanine were also less than those of 4R. We replaced the neutral en ligand by anionic acetylacetonate (acac). The complexes (η6-arene)Os(acac)Cl, arene = biphenyl (6), benzene (7), and p-cymene (8), adopt piano-stool structures similar to those of the RuII analogues and form weak dimers through intermolecular (arene)CH···O(acac) H-bonds. Remarkably, these OsII acac complexes undergo rapid hydrolysis to produce not only the aqua adduct, (η6-arene)Os(acac)(OH2)+, but also the hydroxo-bridged dimer, (η6-arene)Os(μ2-OH)3Os(η6-arene)+. The pKa values for the aqua adducts 6A, 7A, and 8A (7.1, 7.3, and 7.6, respectively) are lower than that for (η6-p-cymene)Ru(acac)(OH2)+ (9.4). Complex 8A rapidly forms adducts with 9-ethylguanine and adenosine, but not with cytidine or thymidine. Despite their reactivity toward nucleobases, complexes 6−8 were inactive toward A549 lung cancer cells. This is attributable to rapid hydrolysis and formation of unreactive hydroxo-bridged dimers which, surprisingly, were the only species present in aqueous solution at biologically relevant concentrations. Hence, the choice of chelating ligand in OsII (and RuII) arene complexes can have a dramatic effect on hydrolysis behavior and nucleobase binding and provides a means of tuning the reactivity and the potential for discovery of anticancer complexes.
Peacock et al. (Thu,) studied this question.