DNA binding properties of combination Co3+, Cu2+, Zn2+ and Pd2+ complexes

Combination therapies are quite common.as anti-cancers, anti-microbials and etc... For instance cisplatin,([PtCl2(NH3)2] or CDDP), is frequently used in combination with one, two, three, or even four otherdrugs, with positive results.[1] Also, kinetic studies of the interaction between DNA and combinations ofthe metal complexes under physiological condition are important for the development of combinationsbased new metallo-pharmaceuticals.[2] Therefore four Co3+, Cu2+, Zn2+ and Pd2+ complexes of formulaK3[Co(ox)3].3H2O (I) (ox=oxalate), [Cu(phen)2Cl]Cl (II), [Zn(phen)3]Cl2 (III), [Pd(phen)2](NO3)2 (IV)(phen=1,10-phenanthroline) were synthesized and characterized analytically and spectroscopically byelemental analysis (C, H, N), FT-IR, UV-Vis, resonance signals in the 1H-NMR and conductivitymeasurements. The interaction each of four series of the metal complexes with calf thymus DNA (CTDNA)were investigated under physiological condition in Tris-HCl buffer using spectroscopic methodsincluding UV-Vis absorption spectroscopy, ethidium bromide displacement and fluorescence titrationspectra. The results obtained from these binding studies indicated that all the series effectively interactwith CT-DNA. Fluorescence titration revealed that the complexes strongly quench DNA bound ethidiumbromide (EB) through static quenching procedures. The Binding constant (Kb), apparent biomolecularquenching constant (Kq) and number of binding sites (n) at different temperatures were determinedaccording to relevant fluorescent data. Thermodynamic parameters, enthalpy change (H), entropychange (S) and Gibss free energy (G) were calculated using Kb and Vant’ Hoff equation. Theseparameters suggested that hydrogen binding and Van der Waals force play the major role in theassociation of each series of metal complexes with CT-DNA.

کلیدواژه ها:

Combination therapy ، DNA binding ، 1 ، 10-phenanthroline