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DNA Phosphodiester Bond Hydrolysis Mediated by Cu(II) and Zn(II) Complexes of 1,3,5,-Triamino-cyclohexane Derivatives
Authors:Claudia Sissi  Fabrizio Mancin  Manlio Palumbo  Paolo Scrimin  Paolo Tecilla  Umberto Tonellato
Affiliation:1. University of Padova, Department of Pharmaceutical Sciences , via Marzolo, 5-35131, Padova, Italy;2. University of Padova, Department of Organic Chemistry and Centro CNR Meccanismi di Reazioni Organiche , via Marzolo 1, 35131, Padova, Italy;3. University of Trieste, Department of Chemical Sciences , via Giorgeri 1, 34127, Trieste, Italy
Abstract:
Abstract

The hydrolytic activity of the 1,3,5-triaminocycloxexane derivatives TACH, TACI and TMCA complexed to Zn(II) and Cu(II) towards a model phosphoric ester and plasmid DNA has been evaluated by means of spectroscopic and gel-electrophoresis techniques. At conditions close to physiological, a prominent cleavage effect mediated by the nature of the ligand and metal ion was generally observed. TACI complexes are the most active in relaxing supercoiled DNA, the effect being explained by the affinity of the hydroxylated ligand for the nucleic acid. As indicated by the dependence of cleavage efficiency upon pH, Zn(II)-complexes act by a purely hydrolytic mechanism. In the case of Cu(II)-complexes, although hydrolysis should be prominent, involvement of an oxidative pathway cannot be completely ruled out.
Keywords:Acyclonucleosides  Pyridothienopyrimidines  Alkylation
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