DNA biding with metallocomplexes of lanthanide (lll) in solution

Abstract

The drugs based on the coordination compounds of metals are constantly developing in the medicinal inorganic chemistry since the discovery of the first platinum anticancer agent cisplatin. Among biologically active metal complexes, lanthanide coordination compounds occupy a special place due to their luminescence properties, as well as antibacterial and anticancer activity. The interaction of metallocomplexes with DNA in solutions is the first and very important step, since DNA is the main target for antitumor drugs of this class.

Four new compounds of different metals with phenanthroline ligands [Tb2(tph)4(OAc)2(phen)2], [Sm2((tph)4(OAc)2(phen)2], [Eu2(tph)4(OAc)2(phen)2] and [Gd2(tph)4(OAc)2(phen)2] and a commercial sample of high molecular calf thymus DNA from Sigma Aldrich Company were used in our research. Phenanthroline can be distinguished among the ligands used in a synthesis of new coordination compounds due to its biological activity itself, and its ability to modify the therapeutic effect of metallocomplexes. The comparison of DNA interaction with free 1,10-phenanthroline and 1,10-phenanthroline in metallocomplexes was performed. The experiments for the detection of the binding of DNA with small compounds were carried out using methods: UV-Vis and fluorescent spectroscopy, low-gradient viscosity, dynamic light scattering and DNA melting. It was shown that all compounds under study can interact with DNA in water-salt solutions. The formation of DNA complexes with compounds is accomplished by direct binding of the phenanthroline ligand to DNA. The equilibrium binding constants were determined. The melting temperature of DNA increases in complexes, and demonstrates the stability of DNA secondary structure. The models of binding are discussed.

Speaker

Komolkina Natalia
Saint Petersburg State University
Russia

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