En Route to Osmium Analogues of KP1019: Synthesis, Structure, Spectroscopic Properties and Antiproliferative Activity of trans-[Os^IVCl₄(Hazole)₂]

By controlled Anderson type rearrangement reactions complexes of the general formula trans-[Os^IVCl₄(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^IVCl₄(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 (H₂ind)[Ru^IIICl₄(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^IVCl₄(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.