Selective DNA Strand Scission with Binuclear Copper Complexes:  Implications for an Active Cu<sub>2</sub>−O<sub>2</sub> Species

Thyagarajan, Sunita; Murthy, Narasimha N.; Sarjeant, Amy A.; Karlin, Kenneth D.; Rokita, Steve E.

doi:10.1021/ja061014t

Cited by 102 publications

(76 citation statements)

References 35 publications

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“…The significant increase in the DNA cleavage activity by 2 in the presence of H 2 O 2 and the inhibition of activity in the presence of DMSO and KI suggest that this reaction is preferentially proceeding by a hydroxy radical mechanism with · OH and hydrogen peroxide species. The oxidative reaction pathway observed here has been suggested previously in the vast majority of DNA cleavage activity by copper complexes [14,15,48,[51][52][53][54][55][56] and in the DNA photocleavage activity by some cobalt(III) complexes. [57] The rate enhancement for DNA cleavage by 2 or its hydrolytic active species [Cu 2 (μ-bdpaT Cl )(H 2 O) 3 Cl] 3+ corresponding to a 2.5 ϫ 10 6 fold increase over the noncatalyzed DNA (k = 1.0 ϫ 10 -11 s -1 at 37°C) [58] reveals the efficiency of this complex to cleave DNA.…”

Section: Cleavage Of Plasmid Dna By 1 Andsupporting

confidence: 65%

DNA Cleavage by Structurally Characterized Dinuclear Copper(II) Complexes Based on Triazine

Massoud

Louka

et al. 2011

Eur J Inorg Chem

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The reaction of 2‐chloro‐4,6‐bis(di‐2‐picolylamino)‐1,3,5‐triazine (bdpaTCl) with copper(II) perchlorate and copper(II) chloride afforded two dinuclear complexes [Cu2(μ‐bdpaTCl)(μ‐OH)2(H2O)0.5(ClO4)0.5](ClO4)1.5·(H2O)1.5 (1) and [Cu2(μ‐bdpaTCl)Cl4]·2CH3OH (2), respectively. These complexes were characterized by IR, UV/Vis, and EPR spectroscopy, single‐crystal X‐ray crystallography, and temperature dependence magnetic susceptibility measurements (2–300 K) as well as by electrochemical and molar conductivity measurements. In 1, each of the three N‐donor atoms of the binucleating bdpaTCl ligand coordinate to CuII ions, which are further bridged by two OH– anions in a distorted five‐coordinate geometry. In addition, each CuII ion forms a Cu–O semicoordinate bond with an aqua ligand or perchlorato anion. The Cu···Cu distance across the hydroxido bridges is 2.9698(11) Å. In 2, the bdpaTCl ligand acts as bis‐tridentate ligand connecting the two CuII ions, and the five‐coordinate geometry around each copper center is achieved by two terminal chloro ligands. Magnetic measurements revealed strong antiferromagnetic coupling in 1 (J = –311.2 cm–1) and very weak coupling in 2 (J = –2.4 cm–1). DNA cleavage by these two complexes has been investigated (pH = 7.0, 37 °C). Although the bridged dihydroxido complex 1 did not show any detectable cleavage for DNA, significant cleavage was observed with the tetrachloro complex 2. Under pseudo‐Michaelis–Menten kinetic conditions, the kinetic parameters kcat = 2.53 × 10–5 s–1 and KM = 1.44 × 10–4 M were determined for 2. The kcat value corresponds to a 2.5 × 106 fold rate enhancement over noncatalyzed DNA. Electrophoretic experiments conducted in the presence and absence of oxidative scavengers DMSO, KI, and NaN3, and radical promoter H2O2 provide evidence for the oxidative cleavage of DNA by hydroxy radicals and hydrogen peroxide species.

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Section: Cleavage Of Plasmid Dna By 1 Andsupporting

confidence: 65%

DNA Cleavage by Structurally Characterized Dinuclear Copper(II) Complexes Based on Triazine

Massoud

Louka

et al. 2011

Eur J Inorg Chem

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“…Oxidative cleavage of DNA by metal complexes can be achieved in the presence of external reagents, while common reductant were ascorbic acid, mercaptopropionic acid (MPA), polyphenol and S(IV) complexes (Patwardhan and Cowan 2001;Jin and Cowan 2005;Lainé et al 2004;Thyagarajan et al 2006;Alipázaga et al 2008). Recent report from our laboratory has shown that 1, 10-phenanthroline/Lthreonine copper (II) complexes with chlorogenic acid as biological reductant can induce DNA oxidative damage (Wang et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Copper (II) complex of 1,10-phenanthroline and l-tyrosine with DNA oxidative cleavage activity in the gallic acid

2011

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Copper (II) complex of formulation [Cu-Phen-Tyr](H(2)O)](ClO(4)) (Phen = 1,10-phenanthroline, L: -Tyr = L: -tyrosine), has been prepared, and their induced DNA oxidative cleavage activity studied. The complex binds to DNA by intercalation, as deduced from the absorption and fluorescence spectral data. Scatchard plots constructed from the absorption titration data gave binding constant 2.44 × 10(4) M(-1) of base pairs. Extensive hypochromism, broadening, and red shifts in the absorption spectra were observed. Upon binding to DNA, the fluorescence from the DNA--ethidium bromide system was efficiently quenched by the copper (II) complex. Stern--Volmer quenching constant 0.61 × 10(3) M(-1) obtained from the linear quenching plots. [Cu-Phen-Tyr] complex efficiently cleave the supercoiled DNA to its nicked circular form with gallic acid as biological reductant at appropriate complex concentration. The gallic acid as reductant could observably improve copper (II) complex to DNA damage. The pseudo-Michaelis-Menten kinetic parameters (k(cat), K(M)) were calculated to be 1.32 h(-1) and 5.46 × 10(-5) M for [Cu-Phen-Tyr] complex. Mechanistic studies reveal the involvement of superoxide anions and hydroxyl radical (HO(·)) as the reactive species under an aerobic medium.

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“…Among several types of transition metal complexes used as synthetic hydrolases, copper(II) and zinc(II) complexes are better suited for the hydrolysis of DNA due to the strong Lewis acid properties of these metal ions. Transition metal complexes containing polypyridylamine-derived ligands have been developed as artificial nucleases, and they displayed versatile DNA cleavage properties in the absence or presence of a redox agent [11][12][13][14][15]. For example, Karlin group [11] has reported a dicopper complex [Cu II 2 (PD 0 O)(H 2 O) 2 ](ClO 4 ) 3 Á2H 2 O (PD 0 O H = 4-tert-butyl-2,6-bis[bis(2-pyridylethyl)-amino]phenol) that predominantly effects DNA base (rather than ribose) oxidation on G residues in single-stranded regions of DNA.…”

Section: Introductionmentioning

confidence: 99%

Four new copper(II) complexes with 1,3-tpbd ligand: Synthesis, crystal structures, magnetism, oxidative and hydrolytic cleavage of pBR322 DNA

Huang

Chen

et al. 2010

Journal of Inorganic Biochemistry

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Selective DNA Strand Scission with Binuclear Copper Complexes: Implications for an Active Cu₂−O₂ Species

Cited by 102 publications

References 35 publications

DNA Cleavage by Structurally Characterized Dinuclear Copper(II) Complexes Based on Triazine

DNA Cleavage by Structurally Characterized Dinuclear Copper(II) Complexes Based on Triazine

Copper (II) complex of 1,10-phenanthroline and l-tyrosine with DNA oxidative cleavage activity in the gallic acid

Four new copper(II) complexes with 1,3-tpbd ligand: Synthesis, crystal structures, magnetism, oxidative and hydrolytic cleavage of pBR322 DNA

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Selective DNA Strand Scission with Binuclear Copper Complexes: Implications for an Active Cu2−O2 Species

Cited by 102 publications

References 35 publications

DNA Cleavage by Structurally Characterized Dinuclear Copper(II) Complexes Based on Triazine

DNA Cleavage by Structurally Characterized Dinuclear Copper(II) Complexes Based on Triazine

Copper (II) complex of 1,10-phenanthroline and l-tyrosine with DNA oxidative cleavage activity in the gallic acid

Four new copper(II) complexes with 1,3-tpbd ligand: Synthesis, crystal structures, magnetism, oxidative and hydrolytic cleavage of pBR322 DNA

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Selective DNA Strand Scission with Binuclear Copper Complexes: Implications for an Active Cu₂−O₂ Species