Osmium NAMI-A Analogues: Synthesis, Structural and Spectroscopic Characterization, and Antiproliferative Properties

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• 作者：Berta Cebriá ; n-Losantos ; Artem A. Krokhin ; Iryna N. Stepanenko ; Rene Eichinger ; Michael A. Jakupec ; Vladimir B. Arion ; Bernhard K. Keppler
• 刊名：Inorganic Chemistry
• 出版年：2007
• 出版时间：June 11, 2007
• 年：2007
• 卷：46
• 期：12
• 页码：5023 - 5033
• 全文大小：378K
• 年卷期：v.46,no.12(June 11, 2007)
• ISSN：1520-510X

文摘

The osmium(III) complex [(DMSO)₂H][trans-Os^IIICl₄(DMSO)₂] (1) has been prepared via stepwise reduction of OsO₄in concentrated HCl using N₂H₄·2HCl and SnCl₂·2H₂O in DMSO. 1 reacts with a number of azole ligands, namely,indazole (Hind), pyrazole (Hpz), benzimidazole (Hbzim), imidazole (Him), and 1H-1,2,4-triazole (Htrz), in organicsolvents, affording novel complexes (H₂ind)[Os^IIICl₄(Hind)(DMSO)] (2), (H₂pz)[Os^IIICl₄(Hpz)(DMSO)] (3), (H₂bzim)[Os^IIICl₄(Hbzim)(DMSO)] (4), (H₂im)[Os^IIICl₄(Him)(DMSO)] (6), and (H₂trz)[Os^IIICl₄(Htrz)(DMSO)] (7), which are closeanalogues of the antimetastatic complex NAMI-A. Metathesis reaction of 4 with benzyltriphenylphosphonium chloridein methanol led to the formation of (Ph₃PCH₂Ph)[Os^IIICl₄(Hbzim)(DMSO)] (5). The complexes were characterizedby IR, UV-vis, ESI mass spectrometry, ¹H NMR spectroscopy, cyclic voltammetry, and X-ray crystallography. Incontrast to NAMI-A, 2-4, 6, and 7 are kinetically stable in aqueous solution and resistant to hydrolysis. Surprisingly,they show reasonable antiproliferative activity in vitro in two human cell lines, HT-29 (colon carcinoma) and SK-BR-3 (mammary carcinoma), when compared with analogous ruthenium compounds. Structure-activity relationshipsand the potential of the prepared complexes for further development are discussed.