Oxidative cleavage of DNA by tridentate copper (II) complex

Copper (II) complex 1 having planar tridentate ligand, bzimpy, where bzimpy is 2,6-bis(benzimidazo-2-yl) pyridine was synthesized and characterized by UV-visible, FAB (fast atom bombardment) mass and infrared spectroscopy. From absorption titration data, the binding constant of Cu(II) with DNA was calculated to be (1.8+/-0.02)x10(4) M(-1). Thermal denaturation study of DNA with 1 revealed deltaT(m) of 5+/-0.5 degrees C. Viscosity measurement showed that complex binds with DNA through intercalative mode. Copper (II) complex induces cleavage in plasmid DNA in the presence of coreductants such as ascorbic acid or glutathione.     

Photooxidation of DNA by a cobalt(II) tridentate complex

[Co(bzimpy)(2)], where bzimpy is 2,6-bis(benzimidazol-2-yl)pyridine was synthesized and characterized by ESI-MS (electrospray ionization mass spectrometry), UV-visible and fluorescence spectra. Absorption titration and thermal denaturation experiments indicate that the complex binds to DNA with moderate strength. Viscosity measurement shows that the mode of binding could be surface binding. Fluorescence study shows that the fluorescence intensity of the complex decreases with increasing concentrations of DNA, which is due to the photoelectron transfer from guanine base to excited MLCT (metal to ligand charge transfer) state of the complex. Photoexcitation of the complex in the MLCT region in the presence of plasmid DNA has been found to give rise to nicking of DNA.     

Synthesis,characterization and DNA binding studies of a ruthenium(II) complex

[Ru(bzimpy)(2)]Cl(2), where bzimpy is 2,6-bis(benzimidazol-2-yl) pyridine was synthesized and characterized by ESI-MS, UV-Visible, (1)H NMR and fluorescence spectra. Absorption titration and thermal denaturation experiments indicate that the complex binds to DNA with moderate strength. Viscosity measurement shows that the mode of binding could be surface binding. Fluorescence study shows that the fluorescence intensity of the complex decreases with increasing concentrations of DNA, which is due to the photoelectron transfer from guanine base to (3)MLCT of the complex. Photoexcitation of the complex in the MLCT region in the presence of plasmid DNA has been found to give rise to nicking of DNA.     

Syntheses, characterization and DNA-binding study of chiral complexes DeltaDelta- and LambdaLambda-[Ru(bpy)2(bdptb)Ru(bpy)2]4+

A novel bridging ligand bdptb(2,2'-bis(5,6-diphenyl-1,2,4-triazin-3-yl)-4,4'-bipyridine) and it's chiral diruthenium(II) complex DeltaDelta- and LambdaLambda-[Ru(bpy)2(bdptb)Ru(bpy)2]4+ (Ru2) have been synthesized and characterized by electrospray mass spectra, 1H NMR, UV/visible and circular dichroism spectra. Binding behavior of these dimeric complexes with calf thymus DNA have been investigated by absorption spectra, viscosity measurements, equilibrium dialysis experiments. The electronic absorption spectra hypochromism at the metal-ligand charge transfer of the DeltaDelta- and LambdaLambda-enantiomer are 26.4%, and 40%, and bathochromism of 13.5, and 14 nm in sequence. Equilibrium dialysis experiments results show also the binding-DNA of LambdaLambda-enantiomer is stronger than DeltaDelta-enantiomer. The increasing amounts of the novel dimeric ruthenium(II) complexes on the relative viscosities of calf thymus DNA is smaller than that of the classic intercalators such as [Ru(bpy)2(dppz)]2+ and larger than that of the non-classic intercalators such as Delta-[Ru(phen)3]2+. The experiments suggest the dimeric ruthenium(II) complex may be bound to DNA by groove binder.     

Synthesis,Characterization, and Cytotoxicity Studies of a Novel Palladium(II) Complex and Evaluation of DNA-Binding Aspects

A new water-soluble palladium(II) complex, [Pd(bpy)(pyr-Ac]NO₃ in which bpy = 2,2′-bipyridine and pyr-Ac is 1-pyrrolacetato, has been synthesized and characterized by spectroscopic methods (¹H NMR, FT-IR, and UV-Vis), molar conductivity measurements, and elemental analysis. The results obtained from elemental analysis and conductivity measurements confirmed the stoichiometry of ligand and its complex while the characteristic peaks in UV-Vis and FT-IR and resonance peaks in ¹H NMR spectra confirmed the formation of ligand frameworks around the palladium ion. The 50% cytotoxic concentration (Ic₅₀) of new synthesized Pd(II) complex was determined by using MTT assay against human breast cancer cell line, T47D. The interaction between the Pd(II) complex with calf thymus DNA was studied at different temperatures by using absorption spectroscopy, fluorescence titration spectra, ethidium bromide displacement, and gel chromatography studies. The results obtained by absorption spectroscopy revealed that the Pd(II) complex can bind to DNA cooperatively at low concentrations. Several binding parameters in the above interaction were calculated by the fluorescence quenching method. The quenching mechanism was suggested to be the static quenching. The thermodynamic parameters: enthalpy change (ΔH °), entropy change (ΔS °), and Gibbs free energy (ΔG °), showed that van der Waals and hydrogen binding are predominant intermolecular forces between Pd(II) complex and DNA. These results were also consistent with the results obtained from Scatchard's plots.     

Cytotoxicity and DNA binding properties of a chloro glycylhistidinate gold(III) complex (GHAu)

The chloro glycylhistidinate gold(III) complex (GHAu) is shown to be fairly cytotoxic towards the established A2780 ovarian carcinoma human cell line either sensitive or resistant to cisplatin. Remarkably, GHAu is far more cytotoxic than the corresponding zinc(II), palladium(II), platinum(II) and cobalt(II) complexes implying that cytotoxicity is essentially to be ascribed to the presence of a gold(III) center. Circular dichroism (CD) spectra, atomic absorption measurements and DNA melting profiles suggest that GHAu in vitro is able to bind DNA, the presumed target for several antitumor metal complexes, and to modify its conformation, even if the observed changes are generally small. Implications of these findings for the mechanism of action of cytotoxic gold(III) complexes are discussed.     

Synthesis, structural characterization and influence on the phagocytic activity of human neutrophils of thiazoline and thiazine derivative ligands and their zinc(II) complexes

The zinc(II) complexes dichloro[2-(3,4-dichlorophenyl)imino-kappaN-(2-thiazolin-kappaN-2-yl)thiazolidine]zinc(II) (1) and dichloro[2-(3,4-dichlorophenyl)imino-kappaN-(4H-5,6-dihydro-1,3-thiazin-kappaN-2-yl)tetrahydrothiazine]zinc(II) (2) have been isolated and characterized in the solid state by X-ray diffraction, elemental analysis and IR spectra. In both complexes, the environment around the zinc(II) ion may be described as a distorted tetrahedral geometry, with the metallic atom coordinated to two chlorine atoms [Zn-Cl(1)=2.218(1)A; Zn-Cl(2)=2.221(1)A], one imino nitrogen [Zn-N(3)=2.042(2)A] and one thiazoline nitrogen [Zn-N(1)=2.022(2)A] in complex 1 and to two chlorine atoms [Zn-Cl(1)=2.216(1)A; Zn-Cl(2)=2.192(1)A], one imino nitrogen [Zn-N(3)=2.045(2)A] and one thiazine nitrogen [Zn-N(1)=2.039(2)A] in complex 2. In addition, we also report in this study the crystal structure of the 2-(3,4-dichlorophenyl)imino-N-(2-thiazolin-2-yl)thiazolidine (TdTn) ligand as well as the synthesis and characterization by X-ray diffraction, (1)H and (13)C NMR spectra, elemental analysis, IR and electronic spectra of the 2-(3,4-dichlorophenyl)imino-N-(4H-5,6-dihydro-1,3-thiazin-2-yl)tetrahydrothiazine (TzTz) ligand. Besides, we study the phagocytic function in humans neutrophils treated with each complex and ligand aforementioned.     

Zinc Z-DNA

Circular dichroism spectra of poly(dG-dC) in the presence of some zinc complexes exhibit the characteristic inversion associated with the formation of a left handed helix. The transition of B to Z DNA is cooperative and slow. The concentration of zinc complex at the mid point of the transition is strongly dependent upon the nature of the ligand bound to zinc. The most efficient species is one with a tetradentate amine for which the mid point is observed at a zinc:nucleotide ratio of 1:24. 31P spectra of one of these complexes confirm the presence of a left handed helix.     

Reaction of N,N-diethyldithiocarbamate and other bidentate ligands with Zn, Co and Cu bovine carbonic anhydrases. Inhibition of the enzyme activity and evidence for stable ternary enzyme-metal-ligand complexes

The reactions with N,N-diethyldithiocarbamate (DDC) of zinc, cobalt and copper carbonic anhydrase from bovine erythrocytes were investigated. The native zinc enzyme was inhibited by DDC, but no removal of zinc could be detected even at a very high [ligand]/[protein] ratio. At identical pH values a larger inhibitory effect was found for the cobalt enzyme. The metal was removed by DDC from the protein at pH less than 7.0. No cobalt removal occurred at pH 10, where a stable ternary complex with the enzyme-bound Co(II) was detected. Its optical and EPR spectra are indicative of five-coordinate Co(II). The reaction of the Cu(II) enzyme with stoichiometric chelating agent was marked by the appearance of an electronic transition at 390 nm (epsilon = 4300 M-1 X cm-1). Metal removal from the copper enzyme readily occurred as the ligand was in excess over the metal, with parallel appearance of a band at 440 nm, which was attributed to the free Cu(II)-DDC complex. Also, in the case of the copper enzyme an alkaline pH was found to stabilize the ternary adduct with the diagnostic 390 nm band. EPR spectra showed that the ternary adduct is a mixture of two species, both characterized by the presence in the EPR spectrum of a superhyperfine structure from two protein nitrogens and by a low g parallel value, indicative of coordination to sulfur ligands. It is suggested that the two species contain the metal as penta- and hexacoordinated, respectively. Measurements of the longitudinal relaxation time, T1, of the water protons suggested that water coordination is retained in the latter case. Hexacoordination with retention of water is also proposed for the Cu(II) derivatives with the bidentate oxalate and bicarbonate anions, unlike the corresponding Co(II) derivatives, which are pentacoordinated. Different coordination of Co(II) and Cu(II) adducts may be relevant to the difference of activity of the two substituted enzymes.     

Preparation and characterization of oxovanadium(IV), acetatomanganese(III), chloroiron(III), nickel(II), copper(II), zinc(II) and palladium(II) complexes of 3,3′-(1,2-phenylenediimino)diacrolein

The oxovanadium(IV), acetatomanganese(III), chloroiron(III), nickel(II), copper(II), zinc(II) and palladium(II) of 3,3′-(1,2-phenylenediimino)diacrolein were prepared and investigated by means of mass, electronic, vibrational, NMR and ESR spectroscopy as well as magnetic susceptibility measurements. The acetatomanganese(III) and chloroiron(III) complexes were confirmed to be of high spin type. The absorption bands appearing in the energy range greater than 23 000 cm⁻¹ were attributed to π→π^* transitions within a ligand molecule and charge- transfer transitions from metal to ligand. The metal complexes assume the square-planar configuration type since the ligand-field bands were detected in the 12 700–18 500 cm⁻¹ region. Strong bands appearing at 1601 and 1627 cm⁻¹ were assigned to the CC and CO stretching vibrational modes, respectively, and were shifted to lower frequency upon metal-coordination. A VO stretching band was observed at 982 cm⁻¹ for the oxovanadium(IV) complex and a CO stretching band was observed at 1547 cm⁻¹ for the acetatomanganese(III) complex. Upon complex formation the amine proton signal is found to vanish and the aldehydic methine proton signal in the lowest field is shifted upfield for the nickel(II), zinc(II) and palladium(II) complexes. ¹³C NMR spectra support the coordination structure of the complexes which is revealed by ¹H NMR spectra. As judged by the spin Hamiltonian parameters, the oxovanadium(IV) complex is of a square- planar type with an unpaired electron in the d_xy orbital and the copper(II) complex assumes a distorted square-planar coordination due to the presence of five- and six-membered chelate rings with an unpaired electron in the d_x2−y2 orbital.     

Synthesis, characterization, and DNA binding of a novel ligand and its Cu(II) complex

A novel naphthalene-2,3-diamine-2-salicylaldehyde (NS) ligand and its mononuclear copper(II) complex (CuNS) have been synthesized and structurally characterized. The UV–vis absorption and emission spectra of NS showed obvious changes on addition of Cu²⁺ solution. The interaction of the compounds with calf thymus DNA and G-quadruplex DNA were investigated by spectroscopic methods and thermal melting assay. The nucleolytic cleavage activity of the compounds was investigated on double-stranded circular pBR322 plasmid DNA and G-quadruplex DNA by electrophoretic mobility shift assay. The results show that CuNS has a greater ability to stabilize G-quadruplex DNA over calf-thymus DNA. The cytotoxicity of the compounds toward HpeG2 cancer cells was also studied, and they showed significant potential for antineoplastic effects.     

DNA binding,cytotoxicity, apoptotic inducing activity,and molecular modeling study of quercetin zinc(II) complex

DNA cleavage activity of quercetin zinc(II) complex has been studied, but little attention has been devoted to the relationship between antitumor activity of this complex and DNA-binding properties. DNA-binding properties of quercetin zinc(II) complex were studied using UV–vis spectra, fluorescence measurements, and viscosity measurements. The results obtained indicate that quercetin zinc(II) complex can intercalate into the stacked base pairs of DNA, and compete with the strong intercalator ethidium bromide for the intercalative binding sites with Stern–Volmer quenching constant, K_sq = 1.24. The complex was subjected to biological tests in vitro using three tumor cell lines (HepG2, SMMC7721, and A549), which showed significant cytotoxicity against three tumor cell lines. Moreover, Hoechst33258 staining showed HepG2 cells underwent the typical morphologic changes of apoptosis characterized by nuclear shrinkage, chromatin condensation, or fragmentation after exposure to the complex. In addition, Molecular modeling was performed to learn the complex could be preferentially bound to DNA in GC region. Our results suggest that antitumor activity of quercetin zinc(II) complex might be related to its intercalation into DNA.     

Active site-specifically reconstituted nickel(II) horse liver alcohol dehydrogenase: Optical spectra of binary and ternary complexes with coenzymes,coenzyme analogues,substrates, and inhibitors

Insertion of nickel ions into the empty catalytic site of horse liver alcohol dehydrogenase yields an active enzyme with 65% metal substitution and about 12% intrinsic activity. The electronic absorption spectrum is characterized by bands at 357 nm (2900 M^?1 cm^?1, 407 nm (3500 M^?1 cm^?1), 505 nm (300 M^?1 cm^?1), 570 nm (?130 M^?1 cm^?1), and 680 nm (?80 M^?1 cm^?1). The absorption and CD spectra are similar to those of nickel(II) azurin and nickel(II) aspartate transcarbamoylase and prove coordination of the nickel(II) ions to sulfur in a distorted tetrahedral coordination geometry. Changes of the spectra upon ligand binding at the metal or conformation changes of the protein induced by coenzyme, or both, indicate alterations of the metal geometry.The chromophoric substrate trans-4-(N, N-dimethylamino)-cinnamaldehyde forms a ternary complex with Ni(II) liver alcohol dehydrogenase and the coenzyme analogue 1,4,5,6-tetrahydronicotinamide-adenine-dinucleotide, stable between pH 6 and 10. The corresponding ternary complex with NADH is only stable at pH > 9.0. The spectral redshifts induced in the substrate are 11 nm larger than those found in the zinc enzyme. We suggest direct coordination of the substrate to the catalytic metal ion which acts as a Lewis acid in both substrate coordination and catalysis.     

Studies on the structure and properties of nickel complexes in a set of amide-based 13-membered macrocyclic ligands

This work reports a systematic investigation to understand the structural, spectroscopic and redox properties of Ni(II) ion in a set of 13-membered amide-based macrocyclic ligands. Four macrocyclic ligands containing e⁻-donating/withdrawing substituents and their Ni(II) complexes have been synthesized and characterized. Structural analysis shows that the macrocyclic ligands create a square-planar environment and nicely accommodate the Ni(II) ion. Electrochemical results suggest that the complexes are capable of undergoing metal-centered oxidation. The electron-donating substituents on ligand lowers the redox potentials and better stabilizes the +3 oxidation state of metal. The electrochemically generated Ni^III species are shown to have rich spectroscopic features. For majority of complexes, the oxidized species are concluded to be Ni^III by their anisotropic EPR spectra typical for Ni^III ion in square-planar geometry. The absorption and EPR spectra for nickel complex bearing an -OMe group on the ligand; however, suggest a Ni(II) complex with a ligand-based radical.     

Zn(II) and Hg(II) complexes of naphthalene based thiosemicarbazone: Structure and spectroscopic studies

Synthesis, structure and spectroscopic characterization of 2-thiophenealdehyde-N(4)-napthylthiosemicarbazone and its complexes with biologically important Zn(II) and toxic Hg(II) metal ions have been reported. The crystal structure of the complexes reveals that both are distorted tetrahedral. In the Hg(II) complex the ligand is neutral and mondented where as in Zn(II) complex the ligand is bidented and anionic. Whereas conductivity measurement study shows both the complexes are molecular species. The beautiful changes in absorption spectra along with isosbestic points upon addition of respective metal salts to the ligand solution convincingly support the formation of metal complexes in solution phase. The other spectroscopic studies also show good correlation with their solid state structures.     

DNA binding, cleavage, and cytotoxic activity of the preorganized dinuclear zinc(II) complex of triazacyclononane derivatives

A preorganized cleft dinuclear zinc(II) complex of 2,6-bis(1-methyl-1,4,7-triazacyclonon-1-yl)pyridine 1 as an artificial nuclease was prepared via an improved method. The interactions of 1, 2 [1,4,7-triazacyclononane (TACN)], and their zinc(II) complexes with calf thymus DNA were studied by spectroscopic techniques, including fluorescence and CD spectroscopy. The results indicate that the DNA binding affinities of these compounds are in the following order: Zn(II)2 -1 > Zn(II) -2 > 1 > 2. The binding constants of the Zn (II)2 -1 and Zn(II)-2 complexes are 3.57 x 10(6) and 1.43 x 10(5) M(-1), respectively. Agarose gel electrophoresis was used to assess the plasmid pUC 19 DNA cleavage activities in the presence of the dinuclear Zn (II)2 -1 complex, which exhibits powerful DNA cleavage efficiency. Kinetic data for DNA cleavage promoted by the Zn(II)2 -1 complex under physiological conditions give the observed rate constant ( k obs) of 0.136 h(-1), which shows an 10(7)-fold rate acceleration over uncatalyzed supercoiled DNA. The comparison of the dinuclear Zn(II)2 -1 complex with the mononuclear zinc(II) complex of 1,4,7-triazacyclononane indicates that the DNA cleavage acceleration promoted by the Zn(II)2 -1 complex is due to the efficient cooperative catalysis of the two proximate zinc(II) cation centers. A hydrolytic mechanism of the cleavage process was suggested, and a preliminary study of the antitumor activity was also conducted.     

DNA sequence-specific ligands: XIII. New Dimeric Hoechst 33258 molecules, inhibitors of HIV-1 integrase in vitro

Dimeric Hoechst 33258 molecules [dimeric bisbenzimidazoles (DBBIs)] that, upon binding, occupy one turn of the B form of DNA in the narrow groove were constructed by computer simulation. Three fluorescent DBBIs were synthesized; they consist of two bisbenzimidazole units tail-to-tail linked to phenolic hydroxy groups via penta- or heptamethylene or tri(ethylene glycol) spacers and have terminal positively charged N.N-dimethylaminopropyl carboxamide groups in the molecule. The absorption spectra of the DBBIs in the presence of different DNA concentrations showed a hypochromic effect and a small shift of the absorption band to longer wavelengths, which indicated the formation of a complex with DNA. The presence of an isobestic point in the spectrum indicates the formation of one type of DBBI-DNA complexes. The interaction of DBBIs with DNA was studied by CD using a cholesteric liquid-crystalline dispersion (CLD) of DNA. The appearance of a positive band in the absorption region of ligand chromophores in the CD spectrum of the DNA CLD indicates the formation of a DBBI-DNA complex in which ligand chromophores are arranged at an angle close to 54 degrees relative to the helix axis of DNA, which suggests the localization of the DBBI in the narrow groove of DNA. All the DBBIs were found to be in vitro inhibitors of HIV-1 DNA integrase in the 3'-processing reaction, and, of the three DBBIs, two dimers inhibit HIV-1 integrase even in submicromolar concentrations.     

Ring-substituted diaqua(1,2-diphenylethylenediamine)platinum(II) sulfate reacts with DNA through a dissociable complex.

Ring-substituted diaqua(1,2-diphenylethylenediamine)platinum(II) sulfate shows unusual kinetics in its reaction with salmon testis DNA. The mechanism for diaqua[meso-1,2-bis(2,6-dichloro-4- hydroxyphenyl)ethylenediamine]platinum(II) sulfate, [Pt(H2O)2(meso-6)]2+SO4(2-), a representative of this series, has been investigated and compared with that for cis-[Pt(NH3)2(H2O)2]2+. Reactions were followed by atomic absorption, analytical HPLC of Pt-DNA digests, arrest of enzymatic DNA synthesis/degradation, ultraviolet and fluorescence spectrophotometry. Except for the formation of monofunctional DNA adducts, the kinetics of the platinum(II) complexes are comparable. The pseudo-first-order rate constant for the attack of DNA by [Pt(H2O)2(meso-6)]2+ follows the concentration of DNA in a hyperbolic fashion, which is in contrast to the linear dependence for cis-[Pt(NH3)2(H2O)2]2+. The hyperbolic dependence is typical for a dissociable DNA/drug complex preceding the coordination reaction. By studying the binding of free ligand to DNA, and by correlating ligand structures and electrostatic charges with effects on adduct formation, both the phenyl residues and the positive charge of the platinum(II) complex are shown to be crucial for the stability of the dissociable complex. A non-intercalative mode of binding to the DNA backbone is suggested. At the high concentrations of DNA found in cell nuclei, the reaction of the dissociable complex can, principally, become rate-limiting in the attack of DNA and thus reduce the cytotoxic efficiency of a drug.     

DNA interaction of some polymer-copper(II) complexes containing 2,2'-bipyridyl ligand and their antimicrobial activities

The water soluble polymer-copper(II) complex samples, [Cu(bpy)(2)(BPEI)]Cl(2).4H(2)O (bpy=2,2'-bipyridine, BPEI=branched polyethyleneimine), with varying degrees of copper(II) chelates content in the polymer chain, were prepared by ligand substitution method in water-ethanol medium and characterized by Infra-red, UV-visible, EPR spectral and elemental analysis methods. The interaction of these polymer-copper(II)-bipyridyl complex samples with calf thymus DNA has been explored by using electronic absorption spectroscopy, emission spectroscopy and gel electrophoresis techniques. The observed changes in the physico-chemical features of the polymer-copper(II) complex on binding to DNA suggest that the complex binds to DNA with electrostatic interaction mode. A sample of polymer-copper(II) complex was tested for its antibacterial and antifungal activity and it was found to have good antibacterial and antifungal activities.     

Metal binding properties of single amino acid deletion mutants of zinc finger peptides: studies using cobalt(II) as a spectroscopic probe.

Peptides corresponding to Cys2His2 zinc finger domains from which one amino acid has been deleted have been synthesized and their metal-binding properties characterized. In contrast to earlier reports (Párraga, G., S. Horvath, L. Hood, E. T. Young, and R. E. Klevit. 1990. Proc. Natl. Acad. Sci. USA. 87:137-141.), such peptides do bind metal ions such as cobalt(II). A peptide with the sequence ProTyrLysCysProGluCysLysSerPheSerGlnLysSerAspLeuValLysHisGlnArgThrHis ThrGly (which corresponds to a previously characterized consensus zinc finger sequence from which a Gly residue immediately following the second Cys residue has been deleted) was found to form a 1:1 peptide to cobalt(II) complex with an absorption spectrum quite similar to those previously observed for zinc finger peptide-cobalt(II) complexes. The dissociation constant for this complex is 6 x 10(-6)M, a factor of 100 times higher than that for the parent peptide. A peptide with the sequence LysProTyrProCysGlyLeuCysArgCysPheThrArgArgAspLeuLeulleArgHisAlaGln - LyslleHisSerGlyAsnLeu corresponding to a similar mutation of the peptide ADR1 was also characterized. Spectroscopic studies with cobalt(II) revealed that this peptide forms both 1:1 and 2:1 peptide to cobalt(II) complexes. The absorption spectra of the two forms and the dissociation constants were determined via deconvolution methods. In contrast, the parent peptide ADR1a was found to form only a 1:1 complex under comparable conditions and this 1:1 complex was found to be more stable than that for the mutant. These results reveal that deletion mutations do adversely affect the stability of zinc finger peptide-metal complexes but that the effects are not as drastic as had been previously described.