Structural characterization of imidazole adducts of heme-DNA complexes

Abstract

Ternary complexes composed of protoheme (heme( Fe3+)) or 13,17-bis(2-carboxylatoethyl)-3,7-diethyl-12,18-trimethyl-2,8-ditrifluoromethylporphyrinatoiron(III) (2,8-DPF( Fe3+)), a parallel G-quadruplex DNA formed from a single repeat sequence of the human telomere, d(TTAGGG), and imidazole (Im), in a ratio of 1:1:1, were prepared and their structures were characterized using optical, circular dichroism, and NMR spectroscopies. The study revealed that heme( Fe3+) and 2,8-DPF( Fe3+) stack onto the 3′-terminal G-quartet of the G-quadruplex DNA, ~0.4 nm apart, and that Im is coordinated to the Fe atom on the side of the heme opposite to the G-quartet in the complex. The stacking of the pseudo-C2symmetric heme( Fe3+) onto the C4symmetric G-quartet in the complex resulted in the formation of two isomers with heme orientations differing by 180° about the pseudo-C2axis, with respect to the DNA. The Im affinity of the 2,8-DPF( Fe3+)-DNA complex was higher by a factor of ~2 than that of the heme( Fe3+)-DNA one, which is possibly due to the stronger ligand-to-metal π donation in the 2,8-DPF( Fe3+) as a result of a decrease in the electron density of the heme Fe atom caused by substitution of the two strongly electron-withdrawing trifluoromethyl groups.