Photo-induced DNA cleavage activity of ternary (N-salicylidene-L-methioninato)copper(II) complexes of phenanthroline bases

Abstract

Copper(II) complexes [Cu(salmet)B] (1-3), where H²salmet is the Schiff base derived from salicylaldehyde and L-methionine and B is heterocyclic bases like 1,10-phenanthroline (phen, 1), dipyridoquinoxaline (dpq, 2) and dipyridophenazine (dppz, 3), are prepared and their DNA cleavage properties studied. Complex [Cu(t)Bu₂salmet)(phen)].CHCl₃ (4.CHCl₃) has been prepared for structural characterization using single crystal X-ray crystallography. Complex 4 has a ternary structure in which the copper displays a distorted square pyramidal (4 + 1) geometry showing tri- and bidentate mode of bonding for the Schiff base and phen, respectively, in CuN₃O₂ coordination. The phen ligand exhibits axial-equatorial mode of bonding, while the dianionic Schiff base binds at the equatorial sites of the basal plane. The one-electron paramagnetic complexes show a d-d band in the electronic spectra in DMF at ca. 670 nm and axial EPR spectral features indicating {d_x2_-y2}¹ ground state in a DMF glass at 77 K. The complexes are redox active displaying quasi-reversible cyclic voltammetric response near 0.1 V (vs. SCE) in DMF-0.1 M TBAP assignable to the Cu(II)/Cu(I) couple. The complexes bind to the calf thymus DNA but to a lesser extent in comparison to bis(phen)copper(II) species that has been used as a standard. The complexes cleave supercoiled (SC) pUC19 DNA in dark under aerobic conditions by oxidative process in presence of mercaptopropionic acid as a reducing agent. They also show photo-induced DNA cleavage on irradiation with UV light of 312 nm or visible green light of 532 nm. The cleavage activity follows the order: 3 ~ 2 > 1. The mechanistic pathways for the DNA cleavage reactions are discussed.