title: 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.
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560 012, India.
authors.forename: Ashis K
authors.initials: AK
authors.lastname: Patra
authors.forename: Tuhin
authors.initials: T
authors.lastname: Bhowmick
authors.forename: Sovan
authors.initials: S
authors.lastname: Roy
authors.forename: Suryanarayanarao
authors.initials: S
authors.lastname: Ramakumar
authors.forename: Akhil R
authors.initials: AR
authors.lastname: Chakravarty
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry* / Q000528:radiation effects; D001665:Binding Sites; D002417:Cattle; D003116:Color; D003300:Copper / Q000737:chemistry* / Q000528:radiation effects; D004247:DNA / Q000737:chemistry / Q000528:radiation effects*; D053960:DNA Breaks / Q000528:radiation effects*; D053837:DNA Cleavage / Q000528:radiation effects*; D006860:Hydrogen Bonding; D008027:Light; D018716:Molecular Mimicry; D009429:Netropsin / Q000737:chemistry* / Q000528:radiation effects; D009942:Organometallic Compounds / Q000737:chemistry / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D009942:Organometallic Compounds; D009429:Netropsin; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; D001120:Arginine