Reactions of potent antitumor complex trans-[RuIIICl 4(indazole)2]- with a DNA-relevant nucleobase and thioethers: Insight into biological action

Alexander Egger, Vladimir B. Arion, Erwin Reisner, Berta Cebrián-Losantos, Sergiu Shova, Günter Trettenhahn, Bernhard K. Keppler

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Reactions of the complex trans-[RuCl4(Hipd)2] - (Hind = indazole), which is of clinical relevance today, with both the DNA model nucleobase 9-methyladenine (made) and the thioethers R 2S (R = Me, Et), as models of the methionine residue in biological molecules possibly acting as nitrogen-competing sulfur-donor ligands for ruthenium atom, have been investigated to get insight into details of mechanism leading to antitumor activity. Three novel ruthenium complexes, viz., [Ru IIICl3(Hind)2(made)], 1, [Ru IIICl2(Hind)2(Me2S)2], 2, and [RuIICl2(Hind)2(Et2S) 2], 3, have been isolated as solids. Oxidation of 2 and 3 with hydrogen peroxide in the presence of 12 M HCl in chloroform afforded the monothioether adducts, viz., [RuIIICl3(Hind) 2(Me2S)], 4, and [RuIIICl3(Hind) 2(Et2S)], 5. By dissolution of 2 or 3 in DMSO, replacemept of both R2S ligapds by DMSO molecules occurred with isolatiop of trans,trans,trans-[RuIICl2(Hind)2(DMSO) 2], 6. The products were characterized by elemeptal apalysis, IR, UV-vis, electrospray mass spectrometry, cyclic voltammetry, and X-ray crystallography (1·CH2Cl2·CH3OH apd 1·1.1 H2O·0..9H3OH, 2, and 5). The first crystallographic evidence for the mopofunctional coordination of the 9-methyladenine ligand to ruthenium via N7 and the self-pairing of the complex molecules via H-bonding, using the usual Watson-Crick pairing donor and acceptor sites of two adjacent 9-methyladenine ligands, is reported. The electrochemical behavior of 1-5 has beep studied in DMF and DMSO by cyclic voltammetry. The redox potential values have been interpreted on the basis of the Lever's parametrization method. The EL parameter was estimated for 9-methyladenine at 0.18 V, showing that this ligand behaves as a weaker net electron donor than imidazole (EL = 0.12 V). The kinetics of the reductively induced stepwise replacement of chlorides by DMF in 4 and 5 were studied by digital simulation of the cyclic voltammograms. The rate constant k1 has been determined as 0.9 ± 0.1 s-1, which obeys the first-order rate law, while k2 is concentration dependent (0.2 ± 0.1 M1-n·S-1 with n > 1 for 4 mM solutions of 4 and 5), indicating higher-order reactions mechanism.
    Original languageEnglish
    Pages (from-to)122-132
    Number of pages10
    JournalInorganic Chemistry: including bioinorganic chemistry
    Volume44
    Issue number1
    DOIs
    Publication statusPublished - 10 Jan 2005

    Keywords

    • Substitution reaction kinetics (coordinative
    • of ruthenium indazole thioether complexes with DMF)
    • Crystal structure
    • Molecular structure
    • Oxidation
    • Redox potential
    • Reduction (of ruthenium indazole complexes with methyladenine and thioethers)
    • Antitumor agents (reactions of potent antitumor complex trans-[RuIIICl4(indazole)2]- with DNA-relevant methyladenine and thioethers)
    • ruthenium indazole methyladenine thioether prepn electrochem
    • crystal structure ruthenium indazole methyladenine thioether
    • antitumor ruthenium indazole complex reaction methyladenine thioether
    • coordinative DMF substitution chloro kinetic ruthenium indazole complex

    Fingerprint

    Dive into the research topics of 'Reactions of potent antitumor complex trans-[RuIIICl 4(indazole)2]- with a DNA-relevant nucleobase and thioethers: Insight into biological action'. Together they form a unique fingerprint.

    Cite this