Osmium NAMI-A analogues: synthesis, structural and spectroscopic characterization, and antiproliferative properties.

Abstract

The osmium(III) complex [(DMSO)2H][trans-OsIIICl4(DMSO)2] (1) has been prepared via stepwise reduction of OsO4 in concentrated HCl using N2H(4).2HCl and SnCl(2).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 organic solvents, affording novel complexes (H2ind)[OsIIICl4(Hind)(DMSO)] (2), (H2pz)[OsIIICl4(Hpz)(DMSO)] (3), (H2bzim)[OsIIICl4(Hbzim)(DMSO)] (4), (H2im)[OsIIICl4(Him)(DMSO)] (6), and (H2trz)[OsIIICl4(Htrz)(DMSO)] (7), which are close analogues of the antimetastatic complex NAMI-A. Metathesis reaction of 4 with benzyltriphenylphosphonium chloride in methanol led to the formation of (Ph3PCH2Ph)[OsIIICl4(Hbzim)(DMSO)] (5). The complexes were characterized by IR, UV-vis, ESI mass spectrometry, 1H NMR spectroscopy, cyclic voltammetry, and X-ray crystallography. In contrast 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 relationships and the potential of the prepared complexes for further development are discussed.

• Authors: Berta Cebrián-Losantos, Artem A Krokhin, Iryna N Stepanenko, Rene Eichinger, Michael A Jakupec, Vladimir B Arion, Bernhard K Keppler
• Journal: Inorganic chemistry (Inorg Chem) Vol. 46 Issue 12 Pg. 5023-33 (Jun 11 2007) ISSN: 0020-1669 [Print] United States
• PMID: 17497853 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Organometallic Compounds
• Osmium Compounds
• Ruthenium Compounds
• imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III)
• Dimethyl Sulfoxide

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dimethyl Sulfoxide (analogs & derivatives, chemistry, pharmacology)
• Drug Stability
• Humans
• Molecular Structure
• Organometallic Compounds (chemistry, pharmacology)
• Osmium Compounds (chemical synthesis, chemistry, pharmacology)
• Ruthenium Compounds
• Spectrum Analysis
• Structure-Activity Relationship