Structures and Catalytic Activities of Complexes between Heme and All Parallel-Stranded Monomeric G-Quadruplex DNAs

Heme in its ferrous and ferric states [heme(Fe²⁺) and heme(Fe³⁺), respectively] binds selectively to the 3'-terminal G-quartet of all parallel-stranded monomeric G-quadruplex DNAs formed from inosine(I)-containing sequences, i.e., d(TAGGGTGGGTTGGGTGIG) DNA(18mer) and d(TAGGGTGGGTTGGGTGIGA) DNA(18mer/A), through a π-π stacking interaction between the porphyrin moiety of the heme and the G-quartet, to form 1:1 complexes [heme-DNA(18mer) and heme-DNA(18mer/A) complexes, respectively]. These complexes exhibited enhanced peroxidase activities, compared with that of heme(Fe³⁺) alone, and the activity of the heme(Fe³⁺)-DNA(18mer/A) complex was greater than that of the heme(Fe³⁺)-DNA(18mer) one, indicating that the 3'-terminal A of the DNA sequence acts as an acid-base catalyst that promotes the catalytic reaction. In the complexes, a water molecule (H₂O) at the interface between the heme and G-quartet is coordinated to the heme Fe atom as an axial ligand and possibly acts as an electron-donating ligand that promotes heterolytic peroxide bond cleavage of hydrogen peroxide bound to the heme Fe atom, trans to the H₂O, for the generation of an active species. The intermolecular nuclear Overhauser effects observed among heme, DNA, and Fe-bound H₂O indicated that the H₂O rotates about the H₂O-Fe coordination bond with respect to both the heme and DNA in the complex. Thus, the H₂O in the complex is unique in terms of not only its electronic properties but also its dynamic ones. These findings provide novel insights into the design of heme-deoxyribozymes and -ribozymes.