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    Phosphate diester cleavage, dna interaction and cytotoxic activity of a bimetallic bis(1,4,7-triazacyclononane) zinc complex

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    Date
    2014-06-24
    Author
    Montagner, Diego
    Gandin, Valentina
    Marzano, Cristina
    Erxleben, Andrea
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    Cited 12 times in Scopus (view citations)
    
    Recommended Citation
    Montagner, Diego; Gandin, Valentina; Marzano, Cristina; Erxleben, Andrea (2014). Phosphate diester cleavage, dna interaction and cytotoxic activity of a bimetallic bis(1,4,7-triazacyclononane) zinc complex. European Journal of Inorganic Chemistry (25), 4084-4092
    Published Version
    http://eprints.maynoothuniversity.ie/7816/1/DM-Phosphate-2014.pdf
    Abstract
    The dinuclear zinc complex [Zn-2{bcmp(-H)}(mu-Cl)](ClO4)(2)center dot H2O {bcmp = 2,6-bis(1,4,7-triazacyclonon-1-ylmethyl)-4-methylphenol} has been synthesized and structurally characterized. The DNA binding affinity was assessed by ethidium bromide fluorescence quenching experiments. The complex relaxes supercoiled pUC19 DNA into the nicked form at low micromolar concentration. Mechanistic studies were carried out using the DNA and RNA models bis(2,4-dinitrophenyl) phosphate (BDNPP) and 2-hydroxypropyl p-nitrophenyl phosphate (HPNP). A detailed kinetic analysis suggested that the bridging OH group of the solution species [Zn-2{bcmp(-H)}(mu-OH)](2+) acts as the nucleophile in the hydrolysis of BDNPP, while in the case of HPNP, the bridging OH group acts as a general base and seems to shift to a terminal position upon substrate coordination. Finally, the cytotoxicity profile of the dinuclear zinc(II) complex was assessed. The complex showed promising in vitro antitumour activity against pancreatic and lung cancers cell lines.
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    http://hdl.handle.net/10379/12949
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