DNA interaction with palladium chelates of biogenic polyamines using atomic force microscopy and voltammetric characterization.

The interaction of double-stranded DNA with two polynuclear Pd(II) chelates with the biogenic polyamines spermidine (Spd) and spermine (Spm), Pd(II)-Spd and Pd(II)-Spm, as well as with the free ligands Spd and Spm, was studied using atomic force microscopy (AFM) at a highly oriented pyrolytic graphite (HOPG) surface, voltammetry at a glassy carbon (GC) electrode, and gel electrophoresis. The AFM and voltammetric results showed that the interaction of Spd and Spm with DNA occurred even for a low concentration of polyamines and caused no oxidative damage to DNA. The Pd(II)-Spd and Pd(II)-Spm complexes were found to induce greater morphological changes in the dsDNA conformation, when compared with their ligands. The interaction was specific, inducing distortion and local denaturation of the B-DNA structure with release of some guanine bases. The DNA strands partially opened give rise to palladium intra- and interstrand cross-links, leading to the formation of DNA adducts and aggregates, particularly in the case of the Pd(II)-Spd complex.

Polynuclear palladium complexes with biogenic polyamines: AFM and voltammetric characterization.

Polynuclear Pd(II) complexes with biogenic polyamines present great potential clinical importance, due to their antiproliferative and cytotoxic activity coupled to less severe side-effects. The adsorption process and the redox behaviour of two polynuclear palladium chelates with spermine (Spm) and spermidine (Spd), Pd(II)-Spm and Pd(II)-Spd, as well as of their ligands Spm and Spd, were studied using atomic force microscopy (AFM) and voltammetry at highly oriented pyrolytic graphite and glassy carbon electrodes. AFM revealed different adsorption patterns and degree of surface coverage, correlated with the chelate structure, concentration of the solution, applied potential and voltammetric behaviour of the Spm, Spd, Pd(II)-Spm and Pd(II)-Spd systems. The voltammetric study of Spm and Spd showed that these biogenic polyamines undergo an irreversible and pH-dependent oxidation. In acid medium the polyamines are fully protonated, rendering their oxidation more difficult. With increasing pH the oxidation potential for both Spm and Spd is shifted to less positive values, indicating a greater ease of oxidation in alkaline medium. The Pd(II)-Spm and Pd(II)-Spd complexes dissociate at high negative or high positive potentials. The application of a positive potential induced the oxidation of these Pd complexes and the formation of mixed layers of palladium oxides, Spm/Spd and Pd(II)-Spm/Pd(II)-Spd.

In situ evaluation of heavy metal-DNA interactions using an electrochemical DNA biosensor.

Heavy metal ions, lead, cadmium and nickel, are well known carcinogens with natural different origins and their direct mode of action is still not fully understood. A dsDNA-electrochemical biosensor, employing differential pulse voltammetry, was used for the in situ evaluation of Pb2+, Cd2+ and Ni2+ interaction with dsDNA. The results confirm that Pb2+, Cd2+ and Ni2+ bind to dsDNA, and that this interaction leads to different modifications in the dsDNA structure. These modifications were electrochemically recognized as changes in the oxidation peaks of guanosine and adenosine bases. Using homopolynucleotides of guanine and adenine it has been proved that the interaction between Pb2+ and DNA causes oxidative damage and preferentially takes place at adenine-containing segments, with the formation of 2,8-dihydroxyadenine, the oxidation product of adenine residues and a biomarker of DNA oxidative damage. The Pb2+ bound to dsDNA can still undergo oxidation. The interaction of Cd2+ and Ni2+ causes conformational changes, destabilizing the double helix, which can enable the action of other oxidative agents on DNA.