Enantioselective DNA binding of iron(II) complexes of methyl-substituted phenanthroline

Abstract

The enantioselective binding of [Fe(4,7-dmp) 3] 2+ (dmp: 4,7-dimethyl-1,10-phenantroline) and [Fe(3,4,7,8-tmp) 3] 2+ (tmp: 3,4,7,8-tetramethyl-1,10-phenanthroline) to calf-thymus DNA (ct-DNA) has been systematically studied by monitoring the circular dichroism (CD) spectral profile of the iron(II) complexes in the absence and presence of ct-DNA. The effect of salt concentration and temperature on the degree of enantioselectivity of the ct-DNA binding of the iron(II) complexes, i.e. the molar ratio of Δ- to Λ-enantiomer in the solution or vice versa has been rigorously evaluated. It is noticeable that Δ-[Fe(4,7-dmp) 3] 2+ and Λ-[Fe(3,4,7,8-tmp) 3] 2+ are preferentially bound to ct-DNA as reflected in their opposite CD spectral profiles. The preferential binding of the Λ-enantiomer of [Fe(3,4,7,8-tmp) 3] 2+ to ct-DNA compared to that of the Δ-enantiomer is associated with the bulkiness of the ancillary ligands due to substitution of four hydrogen atoms in 1,10-phenanthroline for four methyl groups. The determination of enantiomeric inversion constant ( K inv) at various salt concentrations has revealed that the degree of enantioselectivity is salt concentration dependent, indicating that electrostatic interaction is involved in the enantioselective binding of the iron(II) complexes to ct-DNA. Although [Fe(4,7-dmp) 3] 2+ and [Fe(3,4,7,8-tmp) 3] 2+ exhibit an opposite pattern in the CD spectra, the degree of their enantioselectivity ( K inv) is not different from each other significantly. A thermodynamic study on the enantioselective binding of [Fe(4,7-dmp) 3] 2+ to ct-DNA using the van’t Hoff plot of ln K inv versus 1/ T has demonstrated that the enthalpy change (Δ H°) in the inversion process from the Λ- to Δ-enantiomer of [Fe(4,7-dmp) 3] 2+ ct-DNA is positive, indicating that the process is endothermic and thus entropically driven.