Base-specific and enantioselective studies for the DNA binding of iron(II) mixed-ligand complexes containing 1,10-phenanthroline and dipyrido[3,2- a:2′,3′- c]phenazine

Abstract

Base specificity and enantioselectivity for the DNA binding of [Fe(phen) 2(dppz)] 2+ (phen = 1,10-phenanthroline and dppz = dipyrido[3,2- a:2′,3′- c]phenazine) have been studied by determining the equilibrium binding constant ( K b) of the iron(II) complex to calf thymus DNA (ct-DNA), poly[(dA–dT) 2], poly[(dG–dC) 2] and poly[(dI–dC) 2] using spectrophotometric titration and by monitoring the CD spectral profile of the iron(II) complex in the presence and absence of different types of DNA using circular dichroism (CD) spectroscopy, respectively. It has been shown that [Fe(phen) 2(dppz)] 2+ prefers to intercalate into the A–T and I–C sequences of poly[(dA–dT) 2] and poly[(dI–dC) 2] rather than into the G–C sequences of poly[(dG–dC) 2] or into the base pairs of ct-DNA. In contrast to previous reports, it is a surprising observation that the enantioselectivity of the DNA binding for [Fe(phen) 2(dppz)] 2+ is base-dependent in nature. The Δ-enantiomer of [Fe(phen) 2(dppz)] 2+ is preferentially intercalated into the base pairs of poly[(dG–dC) 2] or ct-DNA as indicated by its CD spectral profiles. On the other hand, the Λ-enantiomer of [Fe(phen) 2(dppz)] 2+ is favorably intercalated into poly[(dA–dT) 2] or poly[(dI–dC) 2] as suggested by the opposite CD spectral profile. This preferential binding of Λ-[Fe(phen) 2(dppz)] 2+ for the A–T sequence may be attributed to the fact that the binding site for the A–T sequence is relatively facile and thus the steric effect caused by the ancillary (non-intercalated) phen ligands is alleviated. The degree of enantioselectivity represented by inversion constants ( K inv) decreases as the salt concentration in the solution increases, indicating that electrostatic interaction is also operating in the ct-DNA-binding events of the iron (II) complex.