文摘
Copper(II) complexes [Cu(l-arg)2](NO3)2 (1) and [Cu(l-arg)(B)Cl]Cl (2−5), where B is a heterocyclic base, namely, 2,2′-bipyridine (bpy, 2), 1,10-phenanthroline (phen, 3), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 4), and dipyrido[3,2-a:2′,3′-c]phenazine (dppz, 5), are prepared and their DNA binding and photoinduced DNA cleavage activity studied. Ternary complex 3, structurally characterized using X-ray crystallography, shows a square-pyramidal (4 + 1) coordination geometry in which the N,O-donor l-arginine and N,N-donor 1,10-phenanthroline form the basal plane with one chloride at the elongated axial site. The complex has a pendant cationic guanidinium moiety. The one-electron paramagnetic complexes display a metal-centered d−d band in the range of 590−690 nm in aqueous DMF. They show quasireversible cyclic voltammetric response due to the Cu(II)/Cu(I) couple in the range of −0.1 to −0.3 V versus a saturated calomel electrode in a DMF-Tris HCl buffer (pH 7.2). The DNA binding propensity of the complexes is studied using various techniques. Copper(II) bis-arginate 1 mimics the minor groove binder netropsin by showing preferential binding to the AT-rich sequence of double-strand (ds) DNA. DNA binding study using calf thymus DNA gives an order: 5 (l-arg-dppz) ≥ 1 (bis-l-arg) > 4 (l-arg-dpq) > 3 (l-arg-phen) 2 (l-arg-bpy). Molecular docking calculations reveal that the complexes bind through extensive hydrogen bonding and electrostatic interactions with ds-DNA. The complexes cleave supercoiled pUC19 DNA in the presence of 3-mercaptopropionic acid as a reducing agent forming hydroxyl (•OH) radicals. The complexes show oxidative photoinduced DNA cleavage activity in UV-A light of 365 nm and red light of 647.1 nm (Ar−Kr mixed-gas-ion laser) in a metal-assisted photoexcitation process forming singlet oxygen (1O2) species in a type-II pathway. All of the complexes, barring complex 2, show efficient DNA photocleavage activity. Complexes 4 and 5 exhibit significant double-strand breaks of DNA in red light of 647.1 nm due to the presence of two photosensitizers, namely, l-arginine and dpq or dppz in the molecules.