Fast Hydrolysis and Strongly Basic Water Adducts Lead to Potent Os(II) Half-Sandwich Anticancer Complexes

Abstract

Complexes of the formula [Os(η6-arene)(C,N-phenylpyridine)Z] (where Z is chlorido or a tethered oxygen) undergo very fast Os–Z hydrolysis (<5 min), and the high basicity of the coordinated water molecule of the aqua adducts (Os–OH2; pK a > 8) very much contrasts with previously reported Os-aqua adducts bearing NN- and NO-chelating ligands (pK a < 6). The Os–Cl bond is unreactive in pure DMSO, yet the complexes readily form DMSO adducts upon aquation when dimethyl sulfoxide is present. Such a peculiar aqueous behavior is directly related to the negatively charged CN ligand. Potent Os-CN compounds (but not their Os-NN analogues) are particularly reactive; they bind to cysteine in vitro and decrease the activity of thioredoxin reductase (TrxR) in living cancer cells. By revealing some interesting structure–activity relationship on Os-CN vs Os-NN complexes, we start uncovering the molecular rationale for the successful biological applications of osmium(II) half-sandwich compounds.

Cytotoxicity of osmium(ii) and cycloosmated half-sandwich complexes from 1-pyrenyl-containing phosphane ligands

“…aquation) of Os(II) complexes are slower than for the analogous Ru(II) complexes. [28][29][30][31] Hence, we prepared a series of [OsX 2 (η 6 -pcymene)(P(1-pyrenyl)R 2 R 3 )] complexes (Scheme 1a, M = Os) with diisopropyl-(1-pyrenyl)phosphane or diphenyl-(1-pyrenyl) phosphane as monodentate phosphane ligand (R 2 = R 3 = isopropyl or phenyl) and chloride or iodide as anions (X = Cl or I). Moreover, the corresponding cyclometalated complexes, namely [OsX(η 6 -p-cymene)(k 2 C-(P(1-pyrenyl)R 2 R 3 ))] and [Os(η 6 p-cymene)(k 2 C-(P(1-pyrenyl)R 2 R 3 ))(dmso)]PF 6 , were synthesized as well (Scheme 1b, M = Os).…”