A binuclear copper(II) complex [Cu(L)(NO 3)] 2 ( 1), where L is a NSO-donor reduced Schiff base ligand derived from salicylaldehyde and 2-mercaptoethylamine, is prepared, structurally characterized as 1·0.5MeCN by single crystal X-ray diffraction method and its DNA binding and photo-induced DNA cleavage activity studied. Complex 1 has a diphenoxobridged binuclear structure with a {Cu 2(μ-OAr) 2} core showing CuNO 3S coordination at each metal centre. The redox active complex displays two quasi-reversible cyclic voltammetric responses at 0.26 V ( ΔEp = 390 mV) and at -0.078 V ( ΔEp = 375 mV) versus SCE in DMF-0.1 M TBAP at scan rate of 50 mV s -1 . The complex exhibits a d-d band at 661 nm in DMF and shows moderate binding propensity to calf thymus DNA. It cleaves supercoiled (SC) DNA in the presence of 3-mercaptopropionic acid as a reducing agent. The complex is active in showing photo-induced cleavage of supercoiled pUC19 DNA in UV light of 365 nm and red light of 633 nm (He-Ne laser). The DNA photocleavage reaction involves formation of singlet oxygen ( 1 O2) as the reactive species in a type-II pathway. IPC Code : Int.Cl. 8 C07F1/08
Cobalt(II) complexes of terpyridine bases [Co(L)₂](ClO₄)₂ (1-3), where L is 4'-phenyl-2,2':6',2''-terpyridine (ph-tpy in 1), 4'-(9-anthracenyl)-2,2':6',2''-terpyridine (an-tpy in 2) and 4'-(1- pyrenyl)-2,2':6',2''-terpyridine (py-tpy in 3), are prepared and their photo-induced DNA and protein cleavage activity and photocytotoxic property in HeLa cells studied. The 1 : 2 electrolytic and three-electron paramagnetic complexes show a visible band near 550 nm in DMF-Tris-HCl buffer. The complexes 1-3 show emission spectral bands at 355, 421 and 454 nm, respectively, when excited at 287, 368 and 335 nm. The quantum yield values for 1-3 in DMF-H₂O (2 : 1 v/v) are 0.025, 0.060 and 0.28, respectively. The complexes are redox active in DMF-0.1 M TBAP. The Co(III)-Co(II) and Co(II)-Co(I) couples appear as quasi-reversible cyclic voltammetric responses near 0.2 and -0.7 V vs. SCE, respectively. Complexes 2 and 3 are avid binders to calf thymus DNA giving K(b) value of ∼10⁶ M⁻¹. The complexes show chemical nuclease activity. Complexes 2 and 3 exhibit oxidative cleavage of pUC19 DNA in UV-A and visible light. The DNA photocleavage reaction of 3 at 365 nm shows formation of singlet oxygen and hydroxyl radical species, while only hydroxyl radical formation is evidenced in visible light. Complexes 2 and 3 show non-specific photo-induced bovine serum albumin protein cleavage activity at 365 nm. The an-tpy and py-tpy complexes exhibit significant photocytotoxicity in HeLa cervical cancer cells on exposure to visible light giving IC₅₀ values of 24.2 and 7.6 μM, respectively. Live cell imaging study shows accumulation of the complexes in the cytosol of HeLa cancer cells.
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.
Abstract The design and synthesis of an intensely blue rhodium(III) complex [ 3 ] + of a new N,N‐donor ligand, 8‐(quinolin‐8‐ylamino)pyrido[2,1‐ c ][1,2,4]benzotriazin‐11‐ium, [ 2 ] + , which contains a planar pendant triazinium arm, is described. Structural characterization for [ 3 ] + was carried out by using various spectroscopic techniques and single‐crystal X‐ray crystallography. The organometallic rhodium(III) compound shows a ligand‐based reversible reduction at –0.65 V. The electrochemically reduced compound displays a single‐line EPR spectrum that signifies the formation of ligand‐based free radicals. Compound [ 3 ] + shows a binding propensity to calf thymus DNA to give a K app value of 6.05 × 10 5 M –1 . The parent triazinium salt, pyrido[2,1‐ c ][1,2,4]benzotriazin‐11‐ium [ 1 ] + and the ligand salt [ 2 ] + exhibit photoinduced cleavage of DNA in UV‐A light, whereas the reference Rh complex [ 3 ] + photocleaves DNA with red light (647.1 nm). The compounds show photonuclease activities under both aerobic and anaerobic conditions. Mechanistic investigations under aerobic conditions with several inhibitors indicate the formation of hydroxyl radicals by means of a photoredox pathway. Under anaerobic conditions, it is believed that a photoinduced oxidation of DNA mechanism is operative. Compound [ 3 ] + exhibits photocytotoxicity in HeLa cervical cancer cells to give IC 50 values of (12 ± 0.9) μ M in UV‐A light at 365 nm and (31.4 ± 1.1) μ M in the dark.
Cobalt(III) complexes [Co(pnt)(B)2](NO3)2 (1–3) of pyridine-2-thiol (pnt) and phenanthroline bases (B), viz. 1,10-phenanthroline (phen in 1), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq in 2) and dipyrido[3,2-a:2′,3′-c]phenazine (dppz in 3), have been prepared, characterized and their photo-induced anaerobic DNA cleavage activity studied. The crystal structure of 1a as mixed ClO4− and PF6− salt of 1 shows a CoIIIN5S coordination geometry in which the pnt and phen showed N,S- and N,N-donor binding modes, respectively. The complexes exhibit Co(III)/Co(II) redox couple near −0.3 V (vs. SCE) in 20% DMF–Tris-HCl buffer having 0.1 M TBAP. The complexes show binding propensity to calf thymus DNA giving Kb values within 2.2 × 104–7.3 × 105 M−1. Thermal melting and viscosity data suggest DNA surface and/or groove binding of the complexes. The complexes show significant anaerobic DNA cleavage activity in red light under argon atmosphere possibly involving sulfide anion radical or thiyl radical species. The DNA cleavage reaction under aerobic medium in red light is found to involve both singlet oxygen and hydroxyl radical pathways. The dppz complex 3 shows non-specific BSA and lysozyme protein cleavage activity in UV-A light of 365 nm via both hydroxyl and singlet oxygen pathways. The dppz complex 3 exhibits photocytotoxicity in HeLa cervical cancer cells giving IC50 values of 767 nM and 19.38 μM in UV-A light of 365 nm and in the dark, respectively. A significant reduction of the dark toxicity of the dppz base (IC50 = 8.34 μM in dark) is observed on binding to the cobalt(III) center.
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