Coordination mode and oxidation susceptibility of nickel(II) complexes with 2'-deoxyguanosine 5'-monophosphate and l-histidine

The formation of binary and ternary complexes of Ni(II) with two biologically relevant molecules, 2'-deoxyguanosine 5'-monophosphate (dGMP) and l-histidine (histidine or His) was characterized by potentiometry and UV-visible spectroscopy. For dGMP, the mononuclear complexes with stoichiometries NiH(2)L(+), NiHL and NiL(-) were found. In the mixed system the ternary complexes NiH(2)LA, NiHLA(-) and NiLA(2-) were detected. In binary systems, the Ni(II) ion coordinates to dGMP through the N-7 atom of its purine ring and indirectly through a water molecule bonded to the phosphate group, while in ternary complexes Ni(II) is bonded to all three histidine donors and directly to the phosphate group of dGMP. Both binary and ternary complexes are susceptible to oxidation by H(2)O(2), with the increased formation of 8-oxo-dGMP in the ternary system. The toxicological relevance of these findings stems from possible disturbance by the major biological Ni(II)-His complex of the nucleotide pools homeostasis through the formation of ternary species and oxidation promotion, as well as from 8-oxo-dGMP capacity to inhibit enzymatic elimination of promutagenic oxidized nucleotides from such pools.     

Ternary complexes metal [Co(II), Ni(II), Cu(II) and Zn(II)]--ortho-iodohippurate (I-hip)--acyclovir. X-ray characterization of isostructural [(Co, Ni or Zn)(I-hip)(2)(ACV)(H(2)O)(3)] with stacking as a recognition factor

Four ternary metal--ortho-iodohippurate (I-hip)--acyclovir (ACV) complexes, [M(I-hip)(2)(ACV)(H(2)O)(3)] where M is Co(II) (1), Ni(II) (2), Cu (3) and Zn(II) have been obtained by reaction between the corresponding binary complexes M(II)(I-hip)(2)xnH(2)O and ACV. Three ternary complexes (M=Co, Ni and Zn) and the corresponding Zn(II)--ortho-iodohippurate binary derivative have been structurally characterized by X-ray diffraction: The studies show these three ternary complexes are isostructural and present, in solid state, an interesting stacking between the nucleobase and the aryl ring of the hippurate moiety, which probably promotes the formation of ternary complexes. Moreover, the two different ligands interact between them by means of ancillary hydrogen bonds with water molecules coordinated to the metal ion. It must be mentioned that these two recognition factors, hydrogen bonds plus stacking, could explain the reason for the isostructurality of these ternary derivatives with so different three metal ions, with diverses trends in coordination numbers and geometries. In solid state, there are two enantiomeric molecules that are related by an inversion center as the crystal-building unit (as a translational motif) for the ternary complexes.     

Insertion of dNTPs opposite the 1,N2-propanodeoxyguanosine adduct by Sulfolobus solfataricus P2 DNA polymerase IV

1, N (2)-Propanodeoxyguanosine (PdG) is a stable structural analogue for the 3-(2'-deoxy-beta- d- erythro-pentofuranosyl)pyrimido[1,2-alpha]purin-10(3 H)-one (M 1dG) adduct derived from exposure of DNA to base propenals and to malondialdehyde. The structures of ternary polymerase-DNA-dNTP complexes for three template-primer DNA sequences were determined, with the Y-family Sulfolobus solfataricus DNA polymerase IV (Dpo4), at resolutions between 2.4 and 2.7 A. Three template 18-mer-primer 13-mer sequences, 5'-d(TCACXAAATCCTTCCCCC)-3'.5'-d(GGGGGAAGGATTT)-3' (template I), 5'-d(TCACXGAATCCTTCCCCC)-3'.5'-d(GGGGGAAGGATTC)-3' (template II), and 5'-d(TCATXGAATCCTTCCCCC)-3'.5'-d(GGGGGAAGGATTC)-3' (template III), where X is PdG, were analyzed. With templates I and II, diffracting ternary complexes including dGTP were obtained. The dGTP did not pair with PdG, but instead with the 5'-neighboring template dC, utilizing Watson-Crick geometry. Replication bypass experiments with the template-primer 5'-TCACXAAATCCTTACGAGCATCGCCCCC-3'.5'-GGGGGCGATGCTCGTAAGGATTT-3', where X is PdG, which includes PdG in the 5'-CXA-3' template sequence as in template I, showed that the Dpo4 polymerase inserted dGTP and dATP when challenged by the PdG adduct. For template III, in which the template sequence was 5'-TXG-3', a diffracting ternary complex including dATP was obtained. The dATP did not pair with PdG, but instead with the 5'-neighboring T, utilizing Watson-Crick geometry. Thus, all three ternary complexes were of the "type II" structure described for ternary complexes with native DNA [Ling, H., Boudsocq, F., Woodgate, R., and Yang, W. (2001) Cell 107, 91-102]. The PdG adduct remained in the anti conformation about the glycosyl bond in each of these threee ternary complexes. These results provide insight into how -1 frameshift mutations might be generated for the PdG adduct, a structural model for the exocylic M 1dG adduct formed by malondialdehyde.     

A study on the nickel II-famotidine complexes

Potentiometric studies have shown that Ni(II) forms three pH-dependent complexes with famotidine (L), namely: [NiHL](3+), [NiL](2+) and [NiH(-2)L]. Two of them have been isolated from solution with a Ni/famotidine ratio of 1:1. At pH 6.0, a paramagnetic complex [NiL](2+) with octahedral geometry is formed in which, most likely thiazole N(9) and guanidine N(3) nitrogens are involved in the metal binding. Additionally, two water molecules and two perchlorate anions, ClO(4)(-), fulfil the coordination sphere. The second complex, [NiH(-2)L], that precipitates at pH 8 is diamagnetic and takes square-planar geometry in which four nitrogen donors: N(3), N(9), N(16) and N(20) coordinate to Ni(II). Potentiometric studies, mass spectrometry, FT-IR and Raman spectroscopy are employed to determine and discuss the structure of both complexes. Additionally, 1H, 13C and 15N NMR spectroscopy is used to confirm the binding site in a square-planar complex. The assignment of vibrational bands are made using ab initio HF/CEP-31G method.     

Syntheses, characterization, and microbial activity of some transition metal complexes involving potentially active O and N donor heterocyclic ligands

The formation of binary as well as ternary metal complexes of type MLL′ (where M(II) = Cu(II), Ni(II), Co(II), and Zn(II); L = 8-hydroxyquinoline, and L′ = 2-furoic acid) has been studied. The complexes were synthesized and characterized by elemental analyses, molecular weight determination, the IR and electronic spectra, conductivity, and magnetic measurements. The presence of coordinated water molecules was demonstrated by thermogravimetric analysis. The microbial activity of these ligands and their metal complexes was determined on gram positive (Staphylococcus aureus) and gram negative (Escherichia coli) bacteria, the antifungal activity on some common fungi, viz. Aspergillus niger, Aspergillus nidulense, and Penicillium citrinum.     

Metal(II) binding ability of a novel N-protected amino acid. A solution-state investigation on binary and ternary complexes with 2,2'-bipyridine

The binary and ternary systems 2,2'-bipyridine (bpy)-M(II)-NO2psglyH2 (M(II) = Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Pb(II); NO2psglyH2 = N-(2-nitrophenylsulfonyl)glycine) were investigated in aqueous solution by means of potentiometry and electron spectroscopy in order to identify the type, number and stability of the complex species as a function of pH and metal-to-ligand molar ratio. The aim is to evaluate the effect of a substituent on the phenyl ring of the N-sulfonyl amino acids on their coordination properties. The prevailing species in the binary systems is the [ML] (M = Co(II), Ni(II), Cu(II), Cd(II), Pb(II)) where the amino acid molecule is in the dianionic form and coordinates the metal ion through both carboxylic oxygen and deprotonated sulfonamidic nitrogen, while in the Mn(II)- and Zn(II)-containing binary system the only complex species found are those with the amino acid in the monoanionic form. In the ternary 2,2'-bipyridine-containing systems the chelating coordination mode of the dianionic amino acid is maintained with M(II) = Co(II), Ni(II), Cu(II), Cd(II), Pb(II) and the addition of the aromatic base also enables the Zn(II) ion to substitute for the sulfonamide nitrogen-bound hydrogen of NO2psglyH2.     

Revelation of ternary complexes between redox partners in cytochrome P450-containing monooxygenase systems by the optical biosensor method.

Formation of binary and ternary complexes in the water-soluble cytochrome P450cam (P450cam)-containing as well as in the membrane P4502B4(2B4)- and the mixed P450scc-containing monooxygenase systems was investigated in real time by the 'resonant mirror' optical biosensor method. It was shown that the inter-protein electron transfer occurs not only during complex formation but also upon random collision--as was the case with the d-Fp/d-b5 pair (2B4 system). Binary complexes may be either facilitative to electron transfer (electron-transfer complexes) or prohibitive to it (non-productive complexes). Although the binary PdR/Pd and P450cam/Pd complex formation (within the P450cam-system) as well as the binary AdR/Ad and P450scc/Ad complex formation (within the P450scc-system) does occur, the lifetimes of these complexes formed are several orders of magnitude higher than the time required for realization of a complete hydroxylation cycle. At the same time, the lifetimes of the ternary PdR/Pd/P450cam and AdR/Ad/P450scc complexes are sufficient to permit the realization of a complete hydroxylation cycle in either of these systems. For the membrane P450 2B4 system, the formation of both the binary (Fp/2B4 and 2B4/b5) and ternary (Fp/2B4/b5) complexes was registered. The lifetimes of the binary Fp/2B4 and the ternary Fp/2B4/b5 complexes are sufficient for realization of a complete hydroxylation cycle in each of them.     

Chemical speciation of ternary complexes of L-dopa and 1,10-phenanthroline with Co(II), Ni(II) and Cu(II) in low dielectric media

Abstract

A computer assisted pH-metric investigation has been carried out on the speciation of complexes of Co(II), Ni(II) and Cu(II) with L-dopa and 1,10-phenanthroline. The titrations were performed in the presence of different relative concentrations (M:L:X = 1.0:2.5:2.5; 1.0:2.5:5.0; 1.0:5.0:2.5) of metal (M) to L-dopa (L) and 1,10-phenanthroline (X) with sodium hydroxide in varying concentrations (0-60% v/v) of 1,2-propanediol-water mixtures at an ionic strength of 0.16 mol L^-1 and at a temperature of 303.0 K. Stability constants of the ternary complexes were refined using MINIQUAD75. The species MLXH, MLX, ML₂X and MLX₂H for Co(II) and Cu(II) and MLXH, MLX and MLX₂H for Ni(II) were detected. The extra stability of ternary complexes compared to their binary complexes was believed to be due to electrostatic interactions of the side chains of ligands, charge neutralisation, chelate effect, stacking interactions and hydrogen bonding. The species distribution with pH at different compositions of 1, 2-propanediol-water mixtures and plausible equilibria for the formation of species were also presented. The bioavailability of the metal ions is explained based on the speciation.     

Noncovalent interactions in ternary complexes of spermine and copper(II) with adenosine 5'-triphosphate and tripolyphosphate

Thermodynamic characteristics pertinent to the formation equilibria of two ternary systems: 1) Copper(II), 4,9-diazadodecane-1,12-diamine (spermine, Spe), and adenosine 5'-triphosphate (ATP) and 2) Copper(II), Spe, and tripolyphosphate (TPP) have been determined by means of potentiometric and calorimetric techniques, together with the parent binary complex characteristics. Ternary complexes involving ATP can give information useful in the interpretation of bioenergetic reactions and of biological interactions between nucleic acids and polyamines. As a model system, the TPP-containing ternary complexes have been studied, together with the parent binary complexes. The thermodynamic study of these systems is very important because it can give information about the structural environment of the complexes; moreover, it can help in outlining different noncovalent interactions such as coulombic forces and hydrogen bonds.     

Binding ability of sialic acid towards biological and toxic metal ions. NMR, potentiometric and spectroscopic study.

The binary complexes of 5-amino-3,5-dideoxy-D-glycero-D-galactononulosic acid (NANA), commonly called N-acetyl neuraminic acid, formed with biological metal ions such as Co(II) and Cu(II) and toxic metal ions such as Cd(II) and Pb(II) were investigated in aqueous solution by means of potentiometry, UV and NMR spectroscopy. The corresponding ternary systems with 2,2'-bipyridine were studied in aqueous solution by potentiometry and UV spectroscopy. NANA co-ordinates all metal ions, in both binary and ternary systems through the carboxylic group (protonated or deprotonated according to pH), pyranosidic ring oxygen and glycerol chain alcoholic hydroxy groups. The prevailing species in the pH range 2-7 are of [M(NANA)(2)] type, and their stability constants are greater than those of simple carboxylate complexes. Above pH 7, the species [M(NANA)(2)OH](-) are also formed, but they do not prevent the precipitation of metal hydroxides. This work provides information on the solution state chemistry of NANA in the presence of bivalent metal ions; its great affinity for the toxic metals Cd(II) and Pb(II), near physiological conditions, and the relatively high stability of the complex species found may also account for the mechanism of toxicity.     

Polyphasic character of ATP hydrolysis in actomyosin system.

The interaction of 2-amino-2(hydroxymethyl)-1,3-propanediol (Tris) with the metal ions (M2+) Mg2+, Ca2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Pb2+ was studied by potentiometry and spectrophotometry in aqueous solution (I = 0.1 or 1.0 M, KNO3, 25 degrees C). Stability constants of the M(Tris)2+ complexes were determined; those constants which were measured by both methods agreed well. Ternary complexes containing ATP4- as a second ligand were also investigated and it is shown that in the presence of Tris, mixed-ligand complexes of the type M(ATP)(Tris)2- are formed. The values for delta log KM, where delta log KM = log KM(ATP)M(ATP)Tris--log KMM(Tris), are all negative, thus indicating that the interaction of Tris with M(ATP)2- is somewhat less pronounced than with M2+. However, it should be noted that even in mixed-ligand systems complex formation with Tris may still be considerable, hence great reservations should be exercised in employing Tris as a buffer in systems which also contain metal ions. Distributions of the complex species in dependence on pH are shown for several systems, and the structures of the binary M(Tris)2- and the ternary M(ATP)(Tris)2- complexes are discussed. The participation of a Tris-hydroxo group in complex formation is, at least for the M(Tris)2- species, quite evident.     

Antifungal potential of binary and mixed-ligand complexes of N,2'-diphenyl acetohydroxamic acid.

Chelating potential of N,2'-DPAHA with 3d metal ions such as Cu(II), Ni(II), Zn(II), and Cd(II) in the presence of Gly and Phen has been investigated. These experiments were designed to study the role of the stability of mixed-ligand complexes in the modulation of its fungicidal potential. The mixed-ligand complexes were found to be more stable than binary complexes. Enhanced stability of mixed-ligand complexes of Ni(II), Co(II), Zn(II), and Cd(II) is presumably due to pi-bonding effects. In the stabilization of the Cu(II) mixed-ligand complex system, the Jahn-Tellar effect may play a vital role, in addition to pi-bonding effects. Fungicidal activity of N,2'-DPAHA and its binary complexes with Cu(II), Ni(II), and Co(II) was examined against Fusarium oxysporum using the inhibition zone technique. Binary complexes of Zn(II) and Cd(II) with N,2'-DPAHA and mixed-ligand complexes M(II)-Gly or Phen-N,2'-DPAHA, where M(II) = Cu(II), Ni(II), Zn(II), Co(II), and Cd(II) were screened against Alternaria alternata by slide germination technique. All mixed-ligand complexes exhibited fungicidal activity but did not improve significantly compared to binary complexes. Synergistic action of primary and secondary ligands has increased the stability of the mixed-ligand complex compared to the binary complex (1:1) of the secondary ligand (N,2'-DPAHA), and the fungicidal potential of the mixed-ligand complex involving N,2'-DPAHA as secondary ligand was not increased.     

Copper(II) and nickel(II) ternary complexes of L-dopa and related compounds

The stability constants of the mixed ligand complexes of L-dopa, L-tyrosine, L-phenylalanine, and dopamine with copper(II) and nickel(II) ions and with 2,2'-bipyridyl and 1,10-phenanthroline were determined pH-metrically at 25 degrees C and an ionic strength of 0.2 mol/dm3 (KCl). Spectral studies were made to establish the binding mode of the ambidentate L-dopa in the ternary complexes. In contrast with the aromatic (N,N) donor atoms, the (O,O) binding mode of L-dopa is particularly favored in its ternary systems with copper(II) and nickel(II); thus, even at physiological pH there is a very considerable formation of (O,O)-bound mixed ligand complexes containing a free amino acid side-chain. Numerous binary transition metal-L-dopa complexes and the ternary complexes formed with various B ligands have been evaluated from a coordination chemistry aspect, with regard to the possibility of their therapeutic application in the treatment of Parkinson disease.     

Structural and microbial studies of some transition metal complexes

N-pyridinobenzamide-2-carboxylic acid has been synthesized. Its binary and ternary (using 8-hydroxy-quinoline as the other ligand) Cu(II), Ni(II), Co(II), and Zn(II) complexes have been synthesized and characterized by their elemental analysis, molecular weight determination, molar conductance, infrared and electronic spectral data, and magnetic measurements. Antibacterial activity of these ligands and their metal complexes has been determined on gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria at 37 degrees C, and antifungal activity has been determined on common fungi viz. Aspergillus niger, Aspergillus nidulense, and Candida albicans at 28 degrees C. A considerable increase in the biocidal activity of these ligands on being coordinated with metal ions has been reported.     

Transport of Cu(II) from an albumin mimic peptide, GlyGlyHisGly, to histidine and penicillamine

Cu in blood has been believed to transport into cell via albumin and some amino acids. To shed light on the Cu transport process we studied the reaction of the Cu(II)-peptide with the amino acid by absorption and CD spectra. Albumin mimic peptides GlyGly-L-HisGly (GGHG) and penta-Gly(G5) formed stable 4N coordinated Cu(II) complexes, but in the reaction with histidine (His) and penicillamine (Pes) the ternary Cu(II) complex formations were observed different by the kinetic study. Cu(II)-G5 complexes reacted with Pes to form the ternary complex Cu(H(-1)G5)(Pes(-)) which was subsequently transformed to the binary complex Cu(Pes(-))(2). In the system with GGHG the Cu(II) was also transported from GGHG to Pes, but the ternary Cu(H(-1)GGHG)(Pes(-)) complex as the intermediate was detected a trace. The ternary complex would be spontaneously transformed to Cu(Pes(-))(2) upon forming, because the rate constant of the ternary complex formation k(1+)= approximately 2M(-1)s(-1) was less than k(2+)= approximately 5 x 10(2)M(-1)s(-1) for the Cu(Pes(-))(2) formation at physiological pH. In the Cu(II)-GGHG-His system the ternary Cu(H(-1)GGHG)(His) complex was also hardly identified because the formation constant K(1) and k(1+) were very small and the equilibrium existed between Cu(H(-2)GGHG) and Cu(His)(2) and its overall equilibrium constant beta(2) for Cu(His)(2) was very small to be 1.00+/-0.05 M(-1) at pH 9.0. These results indicated that the ternary complex is formed in the Cu transport process from the albumin to the amino acid, but His imidazole nitrogen in the fourth-binding site of Cu(II) strongly resists the replacement by the incoming ligand.     

Coordination mode of adenosine 5'-diphosphate in ternary systems containing Cu(II), Cd(II) or Hg(II) ions and polyamines

The interactions of adenosine 5'-diphosphate (ADP) with some polyamines (PA) (1,3-diaminopropane (tn), 1,4-diaminobutane (Put), 1,7-diamino-4-azaheptane (3,3-tri) and 1,8-diamino-4-azaoctane (Spd)) both in presence and in the absence of metal ions (Cu(II), Cd(II) and Hg(II)) have been studied. In the metal-free systems the formation of adducts (ADP)Hx(PA) has been observed, in which the main reaction centres are the endocyclic nitrogen atoms of the purine ring, the phosphate group of the nucleotide and the protonated nitrogen atoms of the polyamine. The effectiveness of the phosphate group in formation of adducts has been found to decrease in the series Put > Spd > Spm and to be lower than in the reactions with shorter homologues of biogenic amines. In the ternary systems with metal ions the formation of molecular complexes (ML L' type) has been evidenced in which the protonated polyamine interacts with the nitrogen atoms N(1) or N(7) of the purine ring of the nucleotide. In the ternary systems Cu(II)/ADP/polyamine the coordination dichotomy observed in the binary system Cu(II)/ADP disappears. In the systems with Hg(II) ions the pH range of the dichotomy is extended, while for the systems Cd(II)/ADP/polyamine no changes of the range relative to the binary system Cd(II)/ADP have been noted.     

Study of copper(II) and nickel(II) ternary complexes involving tertiary amines and phenyl or hydroxylphenyl substituted amino acids

Formation constants of ternary complexes MAL, where M = Cu(II) or Ni(II). A = 2.2′bipyridyl. 1, 10-phenanthroline, and L = 3.4-dihydroxyphenylalanine (dopa), tyrosine, or phenylalanine have been determined by using the computer program SCOGS. It is observed that dopa coordinates with Cu(II)-A and Ni(II)-A through the aminocarboxylate and only over the pH range 3–8, though the ligand coordinates with free Cu(II) ion from the amino carboxylate end in the lower pH range (pH 2–4) and from the catechol end at the higher pH range (pH > 5). The visible spectrum of Cu-A-dopa is similar to that of Cu-A-phenylalanine or Cu-A-tyrosine over the entire pH range, confirming amino carboxylate coordination. Δ log K (K_MAL - log_KML) is found to be positive in all the six Cu(II) complexes. whereas it is negative in Ni(II) complexes. Release in the ternary complexes of the repulsion between the Cu(II) dπ electron and electrons delocalized over the phenyl ring has been proposed as a probable reason for the positive Δ log K.     

Spectroscopic studies of ternary complexes of thymidylate synthetase, deoxyribonucleotides, and folate analogs

Conformational changes accompanying the formation of binary and tightly bound ternary complexes of thymidylate synthetase and all possible combinations of three folate analogs (N-10-ethyl-quinazoline, folic acid triglutamate, and folic acid) and three deoxyribonucleotides (5-fluoro-2'-deoxyuridylic acid (FdUMP), 2'-deoxyuridylic acid (dUMP), and thymidylic acid (dTMP] were studied by means of ultraviolet difference spectroscopy. The amplitudes of the spectral changes upon ternary complex formation were 2-3-fold greater than those generated by formation of binary enzyme-nucleotide and enzyme-folate analog complexes. Difference spectra of the ternary complexes all showed a major increase in absorbance in the region of 320-340 nm, presumably due to perturbations of the folate analog chromophores, whereas decreases in absorbance occurred over a range of 260-310 nm. N-10-ethyl-quinazoline tended to form the complex with the greatest filtration efficiency on nitrocellulose filters, followed by folic acid triglutamate and folic acid, whereas among the nucleotides, the most stable complexes were formed with FdUMP, followed by dUMP and dTMP. A correlation was observed between the apparent stability of the ternary complex and the magnitude of the absorbance change in its difference spectrum. The formation of the various ternary complexes showed three different categories of rate behavior: 1) very rapid formation of the complex; 2) biphasic formation with a rapid phase and a slow phase requiring up to 90 min for completion; and 3) in the case of the ternary complex formed with enzyme, FdUMP, and folic acid, only a slow phase of binding. The slow formation of the latter complex was accompanied by concomitantly slow changes in the difference spectrum. However, in those cases of biphasic formation of the complexes, almost all of the spectral change occurred rapidly, and very little of it corresponded to the slow phase of complex formation. To accommodate these observations, a model is proposed involving a sequential interaction of the two subunits of thymidylate synthetase.     

Reversal by nickel(II) of inhibitory effects of some scavengers of active oxygen species upon hydroxylation of 2'-deoxyguanosine in vitro.

Effects of ethanol (EtOH), mannitol (Man), L-histidine (His) and glutathione (GSH) on the oxidation of 2'-deoxyguanosine (dG) to its 8-hydroxy derivative (8-OH-dG) with H2O2 plus L-ascorbic acid (Ascb) in the absence and presence of Ni(II) were investigated in order to unveil the nature of active oxygen species involved in that oxidation. In the absence of Ni(II), production of 8-OH-dG was inhibited by His much greater than GSH greater than or equal to GSSG (oxidized glutathione) much greater than EtOH, but not by Man. The latter tended to enhance the production of 8-OH-dG. In the presence of Ni(II), the inhibition by His, GSH and GSSG, but not EtOH, was prevented. The results indicate involvement of a 'crypto-hydroxyl' radical as the dG oxidizing species in both the absence and presence of Ni(II). Also, the results provide evidence that Ni(II) complexes with His, GSH and GSSG may lack antioxidant capacity. Moreover, the Ni(II) complex with His was found capable of enhancing 8-OH-dG production by the Ascb+H2O2 system to a greater extent than Ni(II) alone. Likewise, although to a lesser extent, the formation of 8-OH-dG was enhanced by the combination of Ni(II) and Man which do not form complexes at pH 7.4. Since His is a major Ni(II) carrier in animal tissues, the dG oxidation enhancing capacity of the Ni(II) complex with His may contribute to the toxic and carcinogenic effects of Ni(II).