Oxidative strand scission of nucleic acids by a multinuclear copper(II) complex

Abstract

The compound [Cu(2)(II)(D(1))(H(2)O)(2)](ClO(4))(4).2H(2)O [D(1)=binucleating ligand with tris(2-pyridylmethyl)amine (TMPA) moieties linked in the 5-pyridyl position by a -CH(2)CH(2)- bridge] mediated efficient oxidative cleavage of pBR322 plasmid DNA under reducing conditions. A mononuclear analogue, [Cu(TMPA)(H(2)O)](ClO(4))(2), was less effective at linearizing supercoiled (Form I) plasmid DNA as compared to the binuclear complex. A new method for quenching the copper-dependent reactions has been developed to avoid plasmid scission by the binuclear complex and the standard gel loading buffer. EDTA was not sufficient for retarding copper reaction, but diethyldithiocarbamic acid was capable of inhibiting all reactivity. Investigation of oxidative cleavage of double-helical oligonucleotides by [Cu(2)(II)(D(1))(H(2)O)(2)](ClO(4))(4) confirmed the enhanced reactivity of the binuclear over the mononuclear complex and provided mechanistic insights into the nature of the reaction. Cleavage of DNA required both the binuclear complex and a reductant and likely proceeded through an O(2)-derived intermediate that does not include a diffusible hydroxyl radical. The greater efficiency of the binuclear complex relative to the mononuclear analogue is consistent with their relative abilities to activate dioxygen.

Catechol Oxidase-like Oxidation Chemistry of the 1–20 and 1–16 Fragments of Alzheimer's Disease-related β-Amyloid Peptide

“…Kinetics and Mechanism of Oxidative Catalysis by CuA␤-To gain further insight into the mechanism for the oxidation activity of CuA␤ 1-20 and its interaction with H 2 O 2 , the catechol analogue 1,2,3-trihydroxylbenzene (THB) was utilized to provide detailed kinetic information owing to its easily accessible oxidation state, which also has been utilized for investigation of oxidative activities of metal complexes (44). The oxidation rate of THB by 7.5 M CuA␤ 1-20 was determined at different values of [THB] in the presence of H 2 O 2 at various concentrations (Fig.…”

μ-Oxamido binuclear copper (II) complexes: Synthesis, crystal structure, DNA interaction and antibacterial studies

“…The Cu(II) centers in close proximity may undergo multielectron reductive cleavage of O 2 to generate an equivalent amount of hydroxyl radicals (HO Å ) [15]. These features were excellently demonstrated by examples reported by Karlin et al, using polynuclear Cu(II) complexes [14,16,17]. Binuclear metal complexes with extended bridged structures exhibit spin exchange and charge transfer between metal ions [18][19][20][21], when such coordination complexes contains DNAbinding moiety that binds either at a groove, or as an intercalator, increases the DNA-targeting ability of the compound.…”

Synthesis and Biophysical Studies of Bis‐Macrocyclic Cobalt/Copper(II) Complexes Having a Pyridine Spacer with CT DNA and 5′‐GMP

“…Therefore, it is reasonable to assume that the complexes bind electrostatically to DNA. The cationic core of 1 and 3 could exert an enhanced electrostatic attraction due to an increase in the positive charge by the incorporation of more than one metal center in a single molecule [52]. The higher the positive charge a dinuclear species possesses, the more cellular uptake is observed [53].…”