Tuning the Reactivity of Osmium(II) and Ruthenium(II) Arene Complexes under Physiological Conditions Anna F. A. Peacock Abraha Habtemariam Rafael Fernández Victoria Walland Francesca P. A. Fabbiani Simon Parsons Rhona E. Aird Duncan I. Jodrell Peter J. Sadler 10.1021/ja055886r.s003 https://acs.figshare.com/articles/dataset/Tuning_the_Reactivity_of_Osmium_II_and_Ruthenium_II_Arene_Complexes_under_Physiological_Conditions/3239014 The Os<sup>II</sup> arene ethylenediamine (en) complexes [(η<sup>6</sup>-biphenyl)Os(en)Cl][Z], Z = BPh<sub>4</sub> (<b>4</b>) and BF<sub>4</sub> (<b>5</b>), are inactive toward A2780 ovarian cancer cells despite <b>4</b> being isostructural with an active Ru<sup>II</sup> analogue, <b>4R</b>. Hydrolysis of <b>5 </b>occurred 40 times more slowly than <b>4R</b>. The aqua adduct <b>5A</b> has a low p<i>K</i><sub>a</sub> (6.3) compared to that of [(η<sup>6</sup>-biphenyl)Ru(en)(OH<sub>2</sub>)]<sup>2+</sup> (7.7) and is therefore largely in the hydroxo form at physiological pH. The rate and extent of reaction of <b>5 </b>with 9-ethylguanine were also less than those of <b>4R</b>. We replaced the neutral en ligand by anionic acetylacetonate (acac). The complexes [(η<sup>6</sup>-arene)Os(acac)Cl], arene = biphenyl (<b>6</b>), benzene (<b>7</b>), and <i>p-</i>cymene (<b>8</b>), adopt piano-stool structures similar to those of the Ru<sup>II</sup> analogues and form weak dimers through intermolecular (arene)CH···O(acac) H-bonds. Remarkably, these Os<sup>II</sup> acac complexes undergo rapid hydrolysis to produce not only the aqua adduct, [(η<sup>6</sup>-arene)Os(acac)(OH<sub>2</sub>)]<sup>+</sup>, but also the hydroxo-bridged dimer, [(η<sup>6</sup>-arene)Os(μ<sup>2</sup>-OH)<sub>3</sub>Os(η<sup>6</sup>-arene)]<sup>+</sup>. The p<i>K</i><sub>a</sub> values for the aqua adducts <b>6A</b>, <b>7A</b>, and <b>8A</b> (7.1, 7.3, and 7.6, respectively) are lower than that for [(η<sup>6</sup>-<i>p</i>-cymene)Ru(acac)(OH<sub>2</sub>)]<sup>+</sup> (9.4). Complex <b>8A</b> rapidly forms adducts with 9-ethylguanine and adenosine, but not with cytidine or thymidine. Despite their reactivity toward nucleobases, complexes <b>6</b>−<b>8</b> 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 Os<sup>II</sup> (and Ru<sup>II</sup>) 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. 2006-02-08 00:00:00 BF p K 549 lung cancer cells 4 R OH Os II acac complexes aqua adduct 5 aqua adducts 6 biphenyl hydrolysis Ru II analogues Ru II analogue Os II arene ethylenediamine