Copper(II) Complexes of l-Arginine as Netropsin Mimics Showing DNA Cleavage Activity in Red Light

Abstract

Copper(II) complexes [Cu(L-arg)(2)](NO(3))(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)> or = 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 ((1)O(2)) 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.

(Dipyrido[3,2-a:2′,3′-c]phenazine)(glycinato)copper(II) perchlorate: A novel DNA-intercalator with anti-proliferative activity against thyroid cancer cell lines

“…[Cu(gly)dppz]ClO 4 (1) (gly = glycinato) was synthesized by modifying a general synthetic method previously reported [33,37]. In detail, a mixture of glycine (75.1 mg, 1.0 mmol) and NaOH (40 mg, 1.0 mmol) in 10 ml of deionized water was added to an aqueous solution (25 ).…”

“…3 has been related to biological activity against Leishmania mexicana [26,32]. Recently, the synthesis and DNA-binding of heteroleptic copper complexes of dppz and amino acids have been reported [33][34][35][36][37]. Such compounds, inter alia, have been proposed as models of bleomycins, naturally occurring anti-tumor glycopeptide antibiotics.…”

Catalytic nanomedicine technology: copper complexes loaded on titania nanomaterials as cytotoxic agents of cancer cell

“…11,12 Various organic ligands coupled to Cu metal, such as terpyridines, 13,14 hydrophilic alkyl phosphine, 15 and moxifloxacin, 16 among others, have been investigated in cancer mechanisms. Although a number of well-defined Cu (II) complexes exhibited DNA degradation capabilities, 17,18 it has been found that the biological activity of some Cu complexes undergoes different mechanisms of action. Apparently, the inhibition of vital cell functions is related to interactions between Cu complexes and enzymes rather than to the induction of cross-linkings between the Cu complexes and DNA.…”

Oxidative DNA cleavage, cytotoxicity and antimicrobial studies of l-ornithine copper (II) complexes

“…The strong binding affinity of the copper bis phen complex and the redox behavior of the copper center play an important role in inducing oxidative DNA cleavage. Chakravarty and co-workers recently explored amino acid transition metal based chemistry towards cleavage of DNA under physiological conditions by oxidative as well as photochemical means on charge transfer or d-d band excitation [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. The copper complex of L-lysine structure is closely resembles the copper-ornithine structure, which shows efficient chemical nuclease activity [25].…”