Bis(dipyridophenazine)copper(II) complex as major groove directing synthetic hydrolase

Abstract

The copper(II) complex [Cu(dppz)2Cl]Cl (1) has been prepared, structurally characterized and its DNA binding and cleavage properties studied (dppz, dipyridophenazine). Crystal structure of 1·dppz·H₂O shows the presence of the monocationic copper(II) complex containing two dppz ligands and one chloride in the five coordinate structure. While one bidentate chelating dppz ligand occupies the basal plane, the other dppz ligand shows an axial/equatorial mode of bonding. The chloride ligand binds at the basal plane. The complex crystallizes with dppz and water as lattice molecules. The dppz moieties in the metal-bound and free forms are involved in π-π stacking interactions. The one-electron paramagnetic complex shows a visible spectral d-d band at 707 nm in DMF and displays quasireversible cyclic voltammetric response for the Cu(II)/Cu(I) couple near 0.1 V vs. SCE in DMF−0.1 M TBAP. The complex which is an avid binder to calf thymus DNA giving a binding constant (K_b) value of 2.0 × 10⁴ M⁻¹ in DMF-Tris buffer, cleaves supercoiled pUC19 DNA in an oxidative manner in the presence of mercaptopropionic acid (MPA) as a reducing agent or on photo irradiation at 312 nm. Control experiments show major groove binding and DNA cleavage via the formation of hydroxyl radical in the presence of MPA and by singlet oxygen in the photocleavage reaction. The complex exhibits significant hydrolytic cleavage of DNA in the dark in the absence of any additives at a rate of ~3.0 h⁻¹. The hydrolytic nature of the DNA cleavage is evidenced from the T4 ligase experiments converting the nicked circular form to its original supercoiled form quantitatively. Complex 1 presents a rare example of copper-based major groove directing efficient synthetic hydrolase.