Influence of several factors on potential-modulated DNA cleavage by the Cu(en)2 and Cu(EDTA) complexes

Potential-modulated DNA cleavage in the presence of copper–ethylenediamine (en) and –ethylenediamine tetraacetic acid (EDTA) complexes was investigated at a gold electrode in a thin layer cell. DNA can be efficiently cleaved through production of active oxygen species at −0.50 V (vs. Ag/AgCl/KCl(sat)) by reducing Cu(en)₂²⁺ to Cu(en)₂⁺ or Cu(EDTA)²⁻ to Cu(EDTA)³⁻. The extent of DNA cleavage increased as the working potential was shifted more negative and the electrolysis time was increased in air-saturated solution. When a small flow of O₂ was passed through the solution during electrolysis, the extent of DNA cleavage was dramatically enhanced. In the absence of Cu(en)₂²⁺ or Cu(EDTA)²⁻ complex, slight DNA cleavage was observed at a more negative working potential due to the reduction of oxygen at the electrode. This observation suggests that potential-modulated DNA cleavage was caused mainly by electrochemical reduction of the Cu(en)₂²⁺ or Cu(EDTA)²⁻ complex in the presence of oxygen. The cleaved DNA fragments were separated by high performance liquid chromatography (HPLC). The experimental results proved that this method of potential-modulated DNA cleavage by Cu(en)₂²⁺ and Cu(EDTA)²⁻ complexes is simple, mild and highly efficient.     

The interaction of copper-bipyridyl complex with DNA and cleavage to DNA.

The interaction of a copper-bipyridyl (bpy) complex with CT-DNA was investigated by voltammetry, absorption and fluorescence spectrophotometry. The binding constant of the Cu(bpy)2(2+) complex interacting with DNA was 3.24 x 10(4) L/mol and the ability binding of Cu(bpy)2(2+) to DNA was 1.3-times as large as that of Cu(bpy)2+ to DNA. DNA could be efficiently cleaved by a potential-modulated method in the presence of the Cu(bpy)2(2+) complex. The fragments of the cleaved DNA were separated by high-performance liquid chromatography (HPLC). The experimental results revealed that the proposed method for DNA cleavage is highly efficient.     

Hydroxyl radical is the active species in photochemical DNA strand scission by bis(peroxo)vanadium(V) phenanthroline

Bis(peroxo)vanadium(V) complexes are widely investigated as anticancer agents. They exert their antitumor and cyctotoxic effects through inhibition of tyrosine phosphatases and DNA cleavage, respectively. The latter process remains poorly understood. The mechanism of DNA cleavage by NH(4)[(phen)V(O)(eta(2)-O(2))(2)] (phen = 1,10-phenanthroline) was investigated. Kinetic studies on DNA cleavage revealed that the complex is a single-strand nicking agent with no specificity. EPR experiments using 2,2,6,6-tetramethyl-4-piperidone (TMP) and 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) as spin-traps for singlet oxygen and hydroxyl radical, respectively, implicated hydroxyl radical production upon photodecomposition of bis(peroxo)vanadium(V). This was corroborated by benzoate inhibition of DNA strand scission and stoichiometric oxidation of 2-propanol to acetone upon irradiation of bis(peroxo)vanadium(V) phenanthroline. High-resolution polyacrylamide gel analysis of the vanadium cleavage reaction and [Fe(II)EDTA](2)(-)/H(2)O(2) resulted in comigration of "ladder" pattern bands, which superimposed when both reactions were run on the same lane. These findings identify hydroxyl radical produced from the photooxidation of the peroxo ligand on vanadium as the active species in DNA cleavage.     

Bis(dipyridophenazine)copper(II) complex as major groove directing synthetic hydrolase

The copper(II) complex [Cu(dppz)(2)Cl]Cl () has been prepared, structurally characterized and its DNA binding and cleavage properties studied (dppz, dipyridophenazine). Crystal structure of 1xdppzxH(2)O shows the presence of the monocationic copper(II) complex containing two dppz ligands and one chloride in the five coordinate structure. While one bidentate chelating dppz ligand occupies the basal plane, the other dppz ligand shows an axial/equatorial mode of bonding. The chloride ligand binds at the basal plane. The complex crystallizes with dppz and water as lattice molecules. The dppz moieties in the metal-bound and free forms are involved in pi-pi stacking interactions. The one-electron paramagnetic complex shows a visible spectral d-d band at 707 nm in DMF and displays quasireversible cyclic voltammetric response for the Cu(II)/Cu(I) couple near 0.1 V vs. SCE in DMF-0.1 M TBAP. The complex which is an avid binder to calf thymus DNA giving a binding constant (K(b)) value of 2.0 x 10(4) M(-1) in DMF-Tris buffer, cleaves supercoiled pUC19 DNA in an oxidative manner in the presence of mercaptopropionic acid (MPA) as a reducing agent or on photo irradiation at 312 nm. Control experiments show major groove binding and DNA cleavage via the formation of hydroxyl radical in the presence of MPA and by singlet oxygen in the photocleavage reaction. The complex exhibits significant hydrolytic cleavage of DNA in the dark in the absence of any additives at a rate of approximately 3.0 h(-1). The hydrolytic nature of the DNA cleavage is evidenced from the T4 ligase experiments converting the nicked circular form to its original supercoiled form quantitatively. Complex presents a rare example of copper-based major groove directing efficient synthetic hydrolase.     

Electrochemical cleavage of DNA in the presence of copper-sulfosalicylic acid complex

Electrochemical cleavage of DNA in the presence of copper-sulfosalicylic acid [Cu(ssal)(2)(2+)] complex was studied. The cleavage was observed in a certain potential region where redox cycling of Cu(ssal)(2)(2+)/Cu(ssal)(2)(+) took place. Cu(ssal)(2)(2+) complex mediate generation of reactive oxygen species from O(2) by the Fenton reaction, these radicals are capable of damaging DNA. The cleaved DNA fragments were separated by high-performance liquid chromatography (HPLC). The experimental results indicated that the method for electrochemical cleavage of DNA by Cu(ssal)(2)(2+) complex was simple and efficient.     

Structure and DNA cleavage properties of two copper(II) complexes of the pyridine-pyrazole-containing ligands mbpzbpy and Hmpzbpya

The DNA-cleavage properties of the two copper(II) complexes, [Cu(mbpzbpy)Br(2)](H(2)O)(2.5) (1) and [Cu(mpzbpya)Cl](CH(3)OH) (2), obtained from the ligands 6,6'-bis(3,5-dimethyl-N-pyrazolmethyl)-2,2'-bipyridine) (mbpzbpy) and 6'-(3,5-dimethyl-N-pyrazolmethyl)-2,2'-bipyridine-6-carboxylic acid) (Hmpzbpya), respectively, are reported. Upon coordination to Cu(II) chloride in methanol, one arm of the ligand mbpzbpy is hydrolyzed to form mpzbpya. Under the same experimental conditions, the reaction of mbpzbpy with CuBr(2) does not lead to ligand hydrolysis. The ligand mpzbpya is coordinated to a copper(ii) ion generating a CuN(3)OCl chromophore, resulting in a distorted square-pyramidal environment, whereas with the N(4) mbpzbpy ligand, the Cu(II) ion is four-coordinated in a distorted square planar geometry. Both complexes promote the oxidative DNA cleavage of phiX174 phage DNA in the absence of reductant. The oxidative nature of the DNA cleavage reaction has been confirmed by religation and cell-transformation experiments. Studies using standard radical scavengers suggest the involvement of hydroxyl radicals in the oxidative cleavage of DNA. Although both compounds do convert form I (supercoiled) DNA to form II (nicked, relaxed form), only complex 1 is able to produce small amounts of form III (linearized DNA). This observation may be explained either by the attack of the copper(ii) complexes to only one single strand of DNA, or by a single cleavage event. Statistical analysis of relative DNA quantities present after the treatment with both copper(ii) complexes supports a random mode of DNA cleavage.     

Designing molecules for PDT: red light-induced DNA cleavage on disulfide bond activation in a dicopper(II) complex

The binuclear copper(II) complex [Cu)(RSSR)2](1), where RSSR is a dianionic Schiff base derived from 2-(thioethyl)salicylaldimine having a disulfide bond is prepared, structurally characterized by X-ray crystallography and its photo-induced DNA cleavage activity studied. The Schiff base ligand H2RSSR is also structurally characterized. The crystal structure of shows the discrete dimeric nature of the complex with each metal showing square-planar geometry with a CuN2O2 coordination (Cu...Cu, 5.011(1)A). The tetradentate Schiff base RSSR acts as a linker of two copper centers. The sulfur atoms in the disulfide unit do not show any apparent interaction with the metal ion. Complex 1, which is cleavage inactive in the dark in the presence of reducing agents, shows significant cleavage of supercoiled pUC19 DNA on exposure to UV light of 312 nm or visible light of different wavelengths under aerobic conditions, in the absence of any additives. DNA cleavage data from control experiments reveal involvement of the disulfide unit as a photosensitizer undergoing photo-induced S-S bond cleavage on exposure to UV light and the resulting species activates molecular oxygen to form singlet oxygen (1O2) that causes DNA cleavage following a type-II process. Photo-induced DNA cleavage by 1 on red-light exposure using a CW laser of 632.8 nm or a pulsed ruby laser of 694 nm is proposed to involve sulfide radicals in a type-I process and hydroxyl radicals as the reactive species.     

Oxidative DNA strand scission induced by a trinuclear copper(II) complex

A novel trinuclear copper(II) complex, Cu3-L (L = N,N,N',N',N' ',N' '-hexakis(2-pyridyl)-1,3,5-tris(aminomethyl)benzene), exhibited efficient oxidative strand scission of plasmid DNA. The solution behavior of the complex has been studied by potentiometric titration, UV spectroscopy, and cyclic voltammetry. The data showed that there are three redox-active copper ions in the complex with three types of bound water. The complex demonstrated a moderate binding ability for DNA. Cu3-L readily cleaves plasmid DNA in the presence of ascorbate to give nicked (form II) and then linear (form III) products, while the cleavage efficiency using H2O2 is less than by ascorbate, suggesting that the cleavage mode of the trinuclear complex is somewhat different from the traditional Fenton-like catalysis. Meanwhile, Cu3-L is far more efficient than its mononuclear analogue Cu-DPA (DPA = 2,2'-dipyridylamine) at the same [Cu2+] concentration, which suggests a possible synergy between the three or at least two Cu(II) centers in Cu3-L that contributes to its relatively high nucleolytic efficiency. Furthermore, the presence of standard radical scavengers does not have clear effect on the cleavage efficiency, suggesting the reactive intermediates leading to DNA cleavage are not freely diffusible radicals.     

A new trick (hydroxyl radical generation) for an old vitamin (B12)

Photolysis of hydroxocobalamin in the presence of plasmid DNA (pBR322) results in DNA cleavage. Temporal control of hydroxyl radical production and DNA strand scission by hydroxocobalamin was demonstrated using a 2-deoxyribose assay and a plasmid relaxation assay, respectively. The light-driven hydroxocobalamin-mediated catalytic formation of hydroxyl radicals was demonstrated using radical scavenging studies of DNA cleavage and via recycling of a hydroxocobalamin-resin conjugate several times without loss of efficacy.     

Synthesis,DNA binding and oxidative cleavage studies of an asymmetric tridentate copper(II) complex

An asymmetric tridentate Cu^II complex, [Cu(ptp)Cl₂] (ptp = 3-(1,10-phenanthrolin-2-yl)-as-triazino[5,6-f]-phenanthrene), has been synthesized and characterized by elemental analysis, FAB-MS, i.r. and u.v.–vis. spectra. The DNA binding behavior of the complex has been examined by fluorescence quenching, cyclic voltammetric and viscosity measurements. The results suggest that [Cu(ptp)Cl₂] binds to DNA in the intercalative mode. This complex is also found to produce cleavage of pBR 322 DNA in the presence of reducing agents such as ascorbate/H₂O₂, and the hydroxyl radical (OH^•) is suggested to be the reactive species responsible for the cleavage.     

Copper complexes as chemical nucleases

Redox active mononuclear and binuclear copper(II) complexes have been prepared and structurally characterized. The complexes have planar N-donor heterocyclic bases like 1,10-phenanthroline (phen), dipyridoquinoxaline (dpq) and dipyridophenazine (dppz) ligands that are suitable for intercalation to B-DNA. Complexes studied for nuclease activity have the formulations [Cu(dpq)₂(H₂O)] (ClO₄)₂.H₂O (1), [CuL(H₂O)₂(μ-ox)](ClO₄)₂ (L = bpy,2; phen,3; dpq,4; and dppz,5) and [Cu(L)(salgly)] (L = bpy,6; phen,7; dpq,8; and dppz,9), where salgly is a tridentate Schiff base obtained from the condensation of glycine and salicylaldehyde. The dpq complexes are efficient DNA binding and cleavage active species. The dppz complexes show good binding ability but poor nuclease activity. The cleavage activity of thebis-dpq complex is significantly higher than thebis-phen complex of copper(II). The nuclease activity is found to be dependent on the intercalating nature of the complex and on the redox potential of the copper(II)/copper(I) couple. The ancillary ligand plays a significant role in binding and cleavage activity.     

Nuclease activity via self-activation and anticancer activity of a mononuclear copper(II) complex: novel role of the tertiary butyl group in the ligand frame

The copper complex [Cu((t)BuPhimp)(Cl)] (1) derived from tridentate ligand (t)BuPhimpH having N(2)O donors was synthesized, and its molecular structure was determined. A phenoxyl radical complex was generated in solution at room temperature using Ce(IV). The nuclease and anticancer activities of 1 were investigated. The roles of the tert-butyl group and singlet oxygen in the DNA cleavage activity were also discussed.     

Factors influencing the DNA nuclease activity of iron, cobalt, nickel, and copper chelates

A library of complexes that included iron, cobalt, nickel, and copper chelates of cyclam, cyclen, DOTA, DTPA, EDTA, tripeptide GGH, tetrapeptide KGHK, NTA, and TACN was evaluated for DNA nuclease activity, ascorbate consumption, superoxide and hydroxyl radical generation, and reduction potential under physiologically relevant conditions. Plasmid DNA cleavage rates demonstrated by combinations of each complex and biological co-reactants were quantified by gel electrophoresis, yielding second-order rate constants for DNA(supercoiled) to DNA(nicked) conversion up to 2.5 × 10(6) M(-1) min(-1), and for DNA(nicked) to DNA(linear) up to 7 × 10(5) M(-1) min(-1). Relative rates of radical generation and characterization of radical species were determined by reaction with the fluorescent radical probes TEMPO-9-AC and rhodamine B. Ascorbate turnover rate constants ranging from 3 × 10(-4) to 0.13 min(-1) were determined, although many complexes demonstrated no measurable activity. Inhibition and Freifelder-Trumbo analysis of DNA cleavage supported concerted cleavage of dsDNA by a metal-associated reactive oxygen species (ROS) in the case of Cu(2+)(aq), Cu-KGHK, Co-KGHK, and Cu-NTA and stepwise cleavage for Fe(2+)(aq), Cu-cyclam, Cu-cyclen, Co-cyclen, Cu-EDTA, Ni-EDTA, Co-EDTA, Cu-GGH, and Co-NTA. Reduction potentials varied over the range from -362 to +1111 mV versus NHE, and complexes demonstrated optimal catalytic activity in the range of the physiological redox co-reactants ascorbate and peroxide (-66 to +380 mV).     

双核铜(Ⅱ)配合物在H2O2存在下对DNA的氧化切割活性

A novel dinuclear copper(Ⅱ) complex, [Cu₂(phen)(dipic)₂(H₂O)₂]·2H₂O (phen=1,10-phenanthroline, dipicH₂=2,6-pyridinedicarboxylic acid), has been prepared and structurally characterized. The complex crystallizes in the triclinic system, space group P1 with cell parameters a=0.846 0(17) nm, b=1.289 5(3) nm, c=1.452 7(3) nm, α=77.42(3)°, β=79.11(3)°, γ=87.08(3)°, and V=1.518 8(6) nm³. The dinuclear complex shows potential DNA cleavage activity at micromolar concentration in the presence of H₂O₂ and exhibits higher nuclease efficiency than mononuclear complex [Cu(dipic)(H₂dipic)]·H₂O. Without external reductants, the added H₂O₂ may contribute to the generation of hydroxyl radicals that result in DNA strand scission.CCDC:291786.     

Studies of copper (Ⅱ) complexes as catalysts for the hydrolysis of DNA

Hydrolysis of DNA is an important enzymatic reaction , but it is exceedingly difficult to mimic in the laboratory because of the stability of hydrolysis of DNA. In this paper, the cleavage activity of complexes formed between Cu(Ⅱ) and four different amino acid or amino acid methyl ester on DNA is studied by gel elec-trophoresis. It is found that DNA could be cleaved by Cu(Ⅱ)-L-His and Cu(Ⅱ)-L-His methyl ester complexes and the efficiency of cleavage is largely dependent on the metal ion-to-ligand ratio. Further experiments show that the cleavage of DNA mediated by Cu(Ⅱ)-L-His complexes occurs via a hydrolytic mechanism and the active chemical species that affects DNA cleavage is proposed to be MI2H and ML2H22 .     

Synthesis,characterization, DNA interaction and cleavage activity of new mixed ligand copper(II) complexes with heterocyclic bases

Mixed ligand complexes having the formulae Cu(RPO)₂Py₂, Cu(RPO)₂Im₂ and Cu(DBO)₂Py₂ [RPO = resacetophenone oxime, DBO = 2,4-dihydroxybenzophenone oxime, Py = pyridine and Im = imidazole] have been synthesized and characterized by UV–Vis, IR, ESR, cyclic voltammetry and magnetic susceptibility methods. Absorption studies revealed that each of these octahedral complexes is an avid binder of calf thymus DNA. The apparent binding constants for mixed ligand complexes are in order of 10⁴–10⁵ M⁻¹. Based on the data obtained in the DNA binding studies a partial intercalative mode of binding is suggested for these complexes. The nucleolytic cleavage activity of the adducts was carried out on double stranded pBR322 circular plasmid DNA by using a gel electrophoresis experiment in the presence and absence of oxidant (H₂O₂). All the metal complexes cleaved supercoiled DNA by hydrolytic and oxidative paths. The oxidative path dominates the hydrolytic cleavage. The hydrolytic cleavage of DNA is evidenced from the control experiments showing discernable cleavage inhibition in the presence of the hydroxyl radical inhibitor DMSO or the singlet oxygen quencher azide ion.     

Influence of stereochemistry and redox potentials on the single- and double-strand DNA cleavage efficiency of Cu(II) and Ni(II) Lys-Gly-His-derived ATCUN metallopeptides

The DNA cleavage chemistry of a series of metallopeptides based on the amino-terminal Cu and Ni (ATCUN) binding motif of proteins has been studied. Specifically, the impact of the positioning of charged Lys side chains and their stereochemistry on metal reduction potentials and DNA cleavage reactivity have been quantitatively evaluated. Both Cu and Ni metallopeptides show a general increase in reactivity toward DNA with an increasing number of Lys residues, while a corresponding decrease in complex reduction potential reflects the enhanced sigma-donor character of the Lys side chain relative to that of Gly. Placement of Lys at the first position in the tripeptide ligand sequence resulted in a greater increase in DNA cleavage reactivity, relative to placement at the second position, while a switch from an l-Lys to a d-Lys typically resulted in enhanced reactivity, as well as perturbations of reduction potential. In the case of Cu peptides, reactivity was enhanced with both increasing positive charge density on the peptide and stabilization of the Cu3+ state. However, for Ni peptides, while the general trends are the same, the correlation with redox behavior was less pronounced. Most likely these differences in specific trends for the Cu and Ni complexes reflect the distinct coordination preferences for Cu3+/2+ and Ni3+/2+ oxidation states, and the consequent distinct positioning of metal-associated reactive oxygen species, as well as the orientation of the DNA-associated complex. Thus, the amino acid composition and stereochemistry of ATCUN metallopeptides can tune the intrinsic reactivities of these systems (their ability to promote formation and activity of metal-associated ROS) as well as their overall structural features, and both of these aspects appear to influence their reactivity and efficiency of DNA strand scission.     

Efficient and specific strand scission of DNA by a dinuclear copper complex: comparative reactivity of complexes with linked tris(2-pyridylmethyl)amine moieties

The compound [Cu(II)(2)(D(1))(H(2)O)(2)](ClO(4))(4) (D(1) = dinucleating ligand with two tris(2-pyridylmethyl)amine units covalently linked in their 5-pyridyl positions by a -CH(2)CH(2)- bridge) selectively promotes cleavage of DNA on oligonucleotide strands that extend from the 3' side of frayed duplex structures at a site two residues displaced from the junction. The minimal requirements for reaction include a guanine in the n (i.e. first unpaired) position of the 3' overhang adjacent to the cleavage site and an adenine in the n position on the 5' overhang. Recognition and strand scission are independent of the nucleobase at the cleavage site. The necessary presence of both a reductant and dioxygen indicates that the intermediate responsible for cleavage is produced by the activation of dioxygen by a copper(I) form of the dinuclear complex. The lack of sensitivity to radical quenching agents and the high level of site selectivity in scission suggest a mechanism that does not involve a diffusible radical species. The multiple metal center exhibits a synergy to promote efficient cleavage as compared to the action of a mononuclear analogue [Cu(II)(TMPA)(H(2)O)](ClO(4))(2) (TMPA = tris(2-pyridylmethyl)amine) and [Cu(OP)(2)](2+) (OP = 1,10-phenanthroline) at equivalent copper ion concentrations. The dinuclear complex, [Cu(II)(2)(D(1))(H(2)O)(2)](ClO(4))(4), is even capable of mediating efficient specific strand scission at concentrations where [Cu(OP)(2)](2+) does not detectably modify DNA. The unique coordination and reactivity properties of [Cu(II)(2)(D(1))(H(2)O)(2)](ClO(4))(4) are critical for its efficiency and site selectivity since an analogue, [Cu(II)(2)(DO)(Cl(2))](ClO(4))(2), where DO is a dinucleating ligand very similar to D(1), but with a -CH(2)OCH(2)- bridge, exhibits only nonselective cleavage of DNA. The differences in the reactivity of these two complexes with DNA and their previously established interaction with dioxygen suggest that specific strand scission is a function of the orientation of a reactive intermediate.     

Two new ternary complexes of copper(II) with tetracycline or doxycycline and 1,10-phenanthroline and their potential as antitumoral: cytotoxicity and DNA cleavage

This paper reports on the synthesis and characterization of two new ternary copper(II) complexes: [Cu(doxycycline)(1,10-phenanthroline)(H(2)O)(ClO(4))](ClO(4)) (1) and [Cu(tetracycline)(1,10-phenanthroline)(H(2)O)(ClO(4))](ClO(4)) (2). These compounds exhibit a distorted tetragonal geometry around copper, which is coordinated to two bidentate ligands, 1,10-phenanthroline and tetracycline or doxycyline, a water molecule, and a perchlorate ion weakly bonded in the axial positions. In both compounds, copper(II) binds to tetracyclines via the oxygen of the hydroxyl group and oxygen of the amide group at ring A and to 1,10-phenanthroline via its two heterocyclic nitrogens. We have evaluated the binding of the new complexes to DNA, their capacity to cleave it, their cytotoxic activity, and uptake in tumoral cells. The complexes bind to DNA preferentially by the major groove, and then cleave its strands by an oxidative mechanism involving the generation of ROS. The cleavage of DNA was inhibited by radical inhibitors and/or trappers such as superoxide dismutase, DMSO, and the copper(I) chelator bathocuproine. The enzyme T4 DNA ligase was not able to relegate the products of DNA cleavage, which indicates that the cleavage does not occur via a hydrolytic mechanism. Both complexes present an expressive plasmid DNA cleavage activity generating single- and double-strand breaks, under mild reaction conditions, and even in the absence of any additional oxidant or reducing agent. In the same experimental conditions, [Cu(phen)(2)](2+) is approximately 100-fold less active than our complexes. These complexes are among the most potent DNA cleavage agents reported so far. Both complexes inhibit the growth of K562 cells with the IC(50) values of 1.93 and 2.59 μmol L(-1) for compounds 1 and 2, respectively. The complexes are more active than the free ligands, and their cytotoxic activity correlates with intracellular copper concentration and the number of Cu-DNA adducts formed inside cells.     

全反式维甲酸合铜(II)配合物对DNA的切割和键合作用

以荧光法、粘度法、凝胶电泳和电化学方法研究了全反式维甲酸合铜(II)配合物与DNA的作用. 结果表明, 该配合物能在生理条件下有效切割质粒DNA, 加入H₂O₂后发现该配合物的切割活性增强, 说明该配合物对DNA的切割机理可能有两种: 氧化和水解. 同时可使DNA的粘度增加, 使EB-DNA体系的荧光强度降低. DNA的存在能导致该配合物氧化还原峰电流降低. 据此推断, 该配合物主要以嵌入方式与DNA作用.