Synthesis, crystal structures, DNA binding and cleavage activity of l-glutamine copper(II) complexes of heterocyclic bases

Abstract

Ternary l-glutamine ( l-gln) copper(II) complexes [Cu( l-gln)(B)(H 2O)](X) (B = 2,2′-bipyridine (bpy), X = 0.5 SO 4 2 - , 1; B = 1,10-phenanthroline (phen), X = ClO 4 - , 2) and [Cu( l-gln)(dpq)(ClO 4)] ( 3) (dpq, dipyridoquinoxaline) are prepared and characterized by physicochemical methods. The DNA binding and cleavage activity of the complexes have been studied. Complexes 1– 3 are structurally characterized by X-ray crystallography. The complexes show distorted square pyramidal (4+1) CuN 3O 2 coordination geometry in which the N,O-donor amino acid and the N,N-donor heterocyclic base bind at the basal plane with a H 2O or perchlorate as the axial ligand. The crystal structures of the complexes exhibit chemically significant hydrogen bonding interactions besides showing coordination polymer formation. The complexes display a d–d electronic band in the range of 610–630 nm in aqueous-dimethylformamide (DMF) solution (9:1 v/v). The quasireversible cyclic voltammetric response observed near −0.1 V versus SCE in DMF–TBAP is assignable to the Cu(II)/Cu(I) couple. The binding affinity of the complexes to calf thymus (CT) DNA follows the order: 3 (dpq) > 2 (phen) ≫ 1 (bpy). Complexes 2 and 3 show DNA cleavage activity in dark in the presence of 3-mercaptopropionic acid (MPA) as a reducing agent via a mechanistic pathway forming hydroxyl radical as the reactive species. The dpq complex 3 shows efficient photo-induced DNA cleavage activity on irradiation with a monochromatic UV light of 365 nm in absence of any external reagent. The cleavage efficiency of the DNA minor groove binding complexes follows the order: 3 > 2 ≫ 1. The dpq complex exhibits photocleavage of DNA on irradiation with visible light of 647.1 nm. Mechanistic data on the photo-induced DNA cleavage reactions reveal the involvement of singlet oxygen ( 1O 2) as the reactive species in a type-II pathway.