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. 2011 Aug 15;50(16):7690-7.
doi: 10.1021/ic200728b. Epub 2011 Jul 8.

En route to osmium analogues of KP1019: synthesis, structure, spectroscopic properties and antiproliferative activity of trans-[Os(IV)Cl4(Hazole)2]

Gabriel E Büchel  1 , Iryna N Stepanenko, Michaela Hejl, Michael A Jakupec, Bernhard K Keppler, Vladimir B Arion
Affiliations
Free PMC article

En route to osmium analogues of KP1019: synthesis, structure, spectroscopic properties and antiproliferative activity of trans-[Os(IV)Cl4(Hazole)2]

Gabriel E Büchel et al. Inorg Chem. .
Free PMC article

Abstract

By controlled Anderson type rearrangement reactions complexes of the general formula trans-[Os(IV)Cl(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(IV)Cl(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(2)ind)[Ru(III)Cl(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(IV)Cl(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.

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Figures

Chart 1
Chart 1. Compounds Reported in This Work
Figure 1
Figure 1
ORTEP view of [OsIVCl4(Hpz)2] (1), [OsIVCl4(Hind)2] (2), [OsIVCl4(Him)2] in 3·2DMSO, and [OsIVCl4(Hbzim)2] (4). Thermal ellipsoids are drawn at 50% probability level.
Figure 2
Figure 2
ORTEP view of trans-[OsIVCl4(Hpz)2]·cucurbit[7]uril in 5·11.25H2O. Thermal ellipsoids are drawn at 50% probability level.
Figure 3
Figure 3
Cyclic voltammogram of 0.2 M solution of 3 in DMSO at a carbon disk working electrode at a scan rate of 0.2 V/s, starting the scan in cathodic direction.
Figure 4
Figure 4
UV–vis spectra of an aqueous solution (containing 1% DMSO) of 4, measured immediately after dissolution and 24 h thereafter.
Figure 5
Figure 5
Concentration–effect curves of compounds 1–4 in (A) A549, (B) CH1, and (C) SW480 cells, obtained by the MTT assay (96 h exposure).
See this image and copyright information in PMC

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