DNA binding of iron(II)-phenanthroline complexes: Effect of methyl substitution on thermodynamic parameters

The influence of methyl substitution on the thermodynamic parameters for the binding of [Fe(DMP)₃]²⁺ and [Fe(TMP)₃] ²⁺ (DMP = 4,7-dimethyl-1,10-phenanthroline, TMP = 3,4,7,8-tetramethyl-1,10-phenanthroline) to calf thymus DNA (ct-DNA) has been studied by determining their equilibrium binding constants (K_b) at various salt concentrations and temperatures. K_b of the iron(II) complexes to ct-DNA decreases with the salt concentration in the solution, suggesting considerable electrostatic interaction in the ct-DNA binding of the iron(II) complexes. In contrast, K_b, of the DNA binding increases with temperature, indicating that the DNA binding reaction of the complex is endothermic and entropically driven. The evaluation of the non-electrostatic binding constant (K_t⁰) based on polyelectrolyte theory has revealed that the K_t⁰ portions of the total binding constant (K_b) are relatively large and reach 46.4% for [Fe(DMP) ₃]²⁺ at [Na⁺] = 0.075 M and 43.9% for [Fe(TMP)₃]²⁺ at [Na⁺] = 0.100 M. The contribution of non-electrostatic binding free energy (ΔG_t ⁰) to total binding free energy change (ΔG⁰) is extremely large, i. e. > 90 % for both iron(II) complexes at [Na⁺] = 0.05 M, suggesting that the stabilization of the DNA binding is mainly contributed from the non-electrostatic process. The effect of methyl substitution on electrostatic (ΔG_pe⁰) and non-electrostatic (ΔG_t⁰) binding free energy changes has been systematically evaluated using the quantity of ΔΔG _pe⁰ and ΔΔG_t⁰ relative to that of the parent iron(II) complex, [Fe(phen)₃]²⁺. The results indicate that the substitution of hydrogen atoms in the phen ligand by methyl groups decreases slightly the electrostatic binding free energy changes, but tremendously increases the non-electrostatic ones to yield net binding free energy changes which are more favorable for the ct-DNA binding.