Dalton Transactions (Print Edition) 2009-02-21

Structural features and oxidative stress towards plasmid DNA of apramycin copper complex.

D Balenci, G Bonechi, N D'Amelio, E Gaggelli, N Gaggelli, E Molteni, G Valensin, W Szczepanik, M Dziuba, G Swiecicki, M Jezowska-Bojczuk

Index: Dalton Trans. (7) , 1123-30, (2009)

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Abstract

The interaction of apramycin with copper at different pH values was investigated by potentiometric titrations and EPR, UV-vis and CD spectroscopic techniques. The Cu(II)-apramycin complex prevailing at pH 6.5 was further characterized by NMR spectroscopy. Metal-proton distances derived from paramagnetic relaxation enhancements were used as restraints in a conformational search procedure in order to define the structure of the complex. Longitudinal relaxation rates were measured with the IR-COSY pulse sequence, thus solving the problems due to signal overlap. At pH 6.5 apramycin binds copper(II) with a 2 : 1 stoichiometry, through the vicinal hydroxyl and deprotonated amino groups of ring III. Plasmid DNA electrophoresis showed that the Cu(II)-apramycin complex is more active than free Cu(II) in generating strand breakages. Interestingly, this complex in the presence of ascorbic acid damages DNA with a higher yield than in the presence of H(2)O(2).