Synthesis and reactivity of the aquation product of the antitumor complex trans-[RuIIICl4(indazole)2]-

Berta Cebrián-Losantos, Erwin Reisner, Christian R. Kowol, Alexander Roller, Sergiu Shova, Vladimir B. Arion, Bernhard K. Keppler

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Aquation of the investigational anticancer drug trans-[Ru IIICl4(Hind)2]- (1, KP1019) results in the formation of mer,trans-[RuIIICl3(Hind) 2(H2O)] (2), which was isolated in high yield (85%) and characterized by spectroscopic methods and X-ray crystallography. Dissolution of 2 in acetone, led to its dimerization into [RuIII 2(μ-Cl)2Cl4(Hind)4]·2(Me) 2CO (3) in 79% yield, with release of two water molecules. Complex 2 reacts readily with nucleophilic organic molecules, viz., methanol or dimethyl sulfide, at room temperature by replacement of the aqua ligand to give mer,trans-[RuIIICl3(Hind)2(MeOH)] (4) and mer,trans-[RuIIICl3(Hind)2(Me2S)] (5) in 58 and 64% yield, respectively. By reaction of 2 with DMSO at room temperature or dimethyl sulfide at elevated temperatures trans,trans,trans- [RuIICl2(Hind)2(Me2S)2] (6) and trans,trans,trans-[RuIICl2(Hind) 2(S-DMSO)2] (7) were prepared in 64 and 75% yield, respectively. Dissolution of 2 in acetonitrile or benzonitrile gave rise to mer,trans-[RuIIICl3(Hind)(HN=C(Me)ind)] (8a), mer,trans-[RuIIICl3(Hind)(HN=C(Ph)ind)] (8b), and trans,trans-[RuIIICl2(HN=C(Me)ind)2]Cl (9) in 67, 50, and 23% yield, respectively, upon metal-assisted iminoacylation of indazole, which is unprecedented for ruthenium(III). Furthermore, complex 2 reacts with the DNA-model bases 9-methyladenine (9-meade) and N6,N6-dimethyladenine (6-me2ade) to yield mer,trans-[Ru IIICl3(Hind)2(9-meade)] (10) and mer,trans-[RuIIICl3(Hind)2(6-me 2ade)] (11) with the purine bases bound to the Ru(III) center via N7 and N3, respectively. Complex 11 represents the first ruthenium complex in which the coordination of the purine ligand N6,N6-dimethyladenine occurs via N3. In addition, the polymer [Na(EtOAc)2RuIII(μ-Cl) 4(Hind)2]n (12) was crystallized from ethyl acetate/diethyl ether solutions of Na[trans-RuIIICl 4(Hind)2]·1.5H2O (1a). The reported complexes were characterized by elemental analysis, IR and UV-vis spectroscopy, ESI mass spectrometry, cyclic voltammetry, and X-ray crystallography. Electrochemical investigations give insight into the mechanistic details of the solvolytic behavior of complex 2. The lability of the aqua ligand in 2 suggests that this complex is a potential active species responsible for the high antitumor activity of trans-[RuIIICl4(Hind) 2]-. © 2008 American Chemical Society.
    Original languageEnglish
    Pages (from-to)6513-6523
    Number of pages10
    JournalInorganic Chemistry: including bioinorganic chemistry
    Volume47
    Issue number14
    DOIs
    Publication statusPublished - 21 Jul 2008

    Keywords

    • Solvolysis kinetics (of aquation product of ruthenium indazole chloro antitumor complex)
    • Reduction
    • Reduction potential (of aquation product of ruthenium indazole chloro antitumor complex and its iminoacylation products and dimethyladenine complex)
    • Crystal structure
    • Molecular structure (of ruthenium chloro complexes with indazole and its iminoacylation products and dimethyladenine)
    • Amidation (prepn. and reactivity and iminoacylation of aquation product of ruthenium indazole chloro antitumor complex)
    • ruthenium indazole adenine complex prepn structure reactivity iminoacylation
    • crystal structure ruthenium indazole adenine complex
    • electrochem redn ruthenium indazole adenine complex

    Fingerprint

    Dive into the research topics of 'Synthesis and reactivity of the aquation product of the antitumor complex trans-[RuIIICl4(indazole)2]-'. Together they form a unique fingerprint.

    Cite this