En route to osmium analogues of KP1019: Synthesis, structure, spectroscopic properties and antiproliferative activity of trans -[Os IVCl 4(Hazole) 2]

Abstract

By controlled Anderson type rearrangement reactions complexes of the general formula trans-[Os IVCl 4(Hazole) 2], where Hazole = 1H-pyrazole, 2H-indazole, 1H-imidazole, and 1H-benzimidazole, have been synthesized. Note that 2H-indazole tautomer stabilization in trans-[Os IVCl 4(2H-indazole) 2] is unprecedented in coordination chemistry of indazole. The metal ion in these compounds possesses the same coordination environment as ruthenium(III) in (H 2ind) [Ru IIICl 4(Hind) 2], where Hind = 1H-indazole, (KP1019), an investigational anticancer drug in phase I clinical trials. These osmium(IV) complexes are appropriate precursors for the synthesis of osmium(III) analogues of KP1019. In addition the formation of an adduct of trans-[Os IVCl 4(Hpz) 2] with cucurbit[7]uril is described. The compounds have been comprehensively characterized by elemental analysis, EI and ESI mass spectrometry, spectroscopy (IR, UV-vis, 1D and 2D NMR), cyclic voltammetry, and X-ray crystallography. Their antiproliferative acitivity in the human cancer cell lines CH1 (ovarian carcinoma), A549 (nonsmall cell lung carcinoma), and SW480 (colon carcinoma) is reported. © 2011 American Chemical Society.