Identification and structural characterization of febuxostat metabolites in rat serum and urine samples using UHPLC–QTOF/MS

Febuxostat is a novel nonpurine type of highly selective xanthine oxidoreductase inhibitor. A rapid and sensitive ultra‐high‐performance liquid chromatography–quadrupole time‐of‐flight mass spectrometry method for simultaneous separation and determination of febuxostat and its metabolites in rat serum and urine was developed at various time points after oral administration to the rats. The febuxostat metabolites were predicted by biotransformation software and transformed to a personal compound database to quickly determine the possible metabolites from the MS1 data. The possibility of the MS/MS fragmentation was calculated by the Molecular Structure Correlator software. As a result, five phase I and two phase II metabolites in rat serum, and seven phase I and three phase II metabolites in rat urine were identified, of which four metabolites (M2, M5, M6, M7) have not been reported before. The metabolite toxicities are predicted, and the results are helpful for the design of new xanthine oxidoreductase inhibitors.     

Molecular epidemiological investigation of Ascaris genotypes in China based on single-strand conformation polymorphism analysis of ribosomal DNA

Using a single-strand conformation polymorphism-based approach, we investigated nucleotide variation in part of the first internal transcribed spacer (pITS-1) of nuclear ribosomal DNA within and among a large number of Ascaris individuals from humans and pigs from six endemic regions in China, and examined the frequency of the different genotypes of Ascaris in relation to host species and geographical origin. Five different SSCP genotypes (G1-G5) were recorded for human Ascaris (n = 486), of which three (genotypes G1-G3) were detected for pig Ascaris (n = 329). Of the five Ascaris genotypes detected, genotype G1 predominantly infected humans (approximately 63-74%) whereas genotype G3 infected mainly pigs (approximately 79-86%), indicating that each of these genotypes has a particular host affiliation. In contrast, the frequencies of the other three genotypes was substantially lower for each of the two host species. The findings also suggested that the rate of cross infection of Ascaris between humans and pigs is relatively low and that gene flow between the predominant genotypes is limited, consistent with previous proposals for endemic regions in other countries. While the nature and extent of nucleotide variation in the pITS-1 (and the proposal of host affiliated Ascaris populations) may relate to "introgression" or "lineage sorting and retention of ancentral polymorphism", other explanations are possible. Evidence of multiple pITS-1 sequence types in some Ascaris individuals representing particular genotypes (e.g., G2 and G5) may suggest hybridization between human- and pig-affiliated Ascaris. This aspect and the species status of Ascaris (from each host species) warrant future experimental testing, employing the pig/Ascaris model and the present electrophoretic approach.*     

Kinetic study of the effects of inhibitors on the catalyzed dehydration of HCO3- by copper(II) complexes [TpPh]CuX (X- = OH-, N3-, NCS-)

A series of half-sandwich copper(II) complexes [TpPh]CuX ([TpPh] = hydrotris(3-phenyl-pyrazolyl)borate; X- = OH- (1), N3- (2), NCS- (3)) have been synthesized as models for carbonic anhydrase. The structure of 3 was determined by X-ray diffraction analysis. Crystals of 3 (C37H30BCuN9S) are triclinic, space group P1 with a = 11.997(3) A, b = 12.116(3) A, c = 13.384(4) A, alpha = 81.088(5) degrees, beta = 79.289(6) degrees, gamma = 68.668(5) degrees, V = 1772.4(8) A3, and Z = 2. The dehydration kinetic measurements of HCO3- are performed by the stopped-flow techniques at pH < 7.9. The apparent dehydration rate constant kdobs varies linearly with total Cu(II) concentration, and the catalytic activity of the model complexes decreases in the order 1 > 2 > 3. The catalytic activity decreases with increasing pH indicating that the aqua model complex must be the reactive catalytic species in the catalyzed dehydration reaction and the rate-determining step is the substitution of the labile water molecule by HCO3-. The kdobs values increase with increasing reaction temperature, and the apparent activation energies of the model complexes with inhibitors are remarkably higher than that of the complex with no inhibitors, this being the origin of inhibition. The large negative entropy of activation also indicates an associative mode of activation in the rate-determining step. The inhibition ability of the inhibitor NCS- is stronger than that of the inhibitor N3-, which can be rationalized by the decrease in effective atomic charges of the Cu(II) ions as revealed by the theoretical calculations.     

Light activation of a cysteine protease inhibitor: caging of a peptidomimetic nitrile with Ru(II)(bpy)2

A novel method for caging protease inhibitors is described. The complex [Ru(II)(bpy)(2)(1)(2)](PF(6))(2) (2) was prepared from the nitrile-based peptidomimetic inhibitor Ac-Phe-NHCH(2)CN (1). (1)H NMR, UV-vis, and IR spectroscopic and mass spectrometric data confirmed that 2 equiv of inhibitor 1 bind to Ru(II) through the nitrile functional group. Complex 2 shows excellent stability in aqueous solution in the dark and fast release of 1 upon irradiation with visible light. As a result of binding to the Ru(II) center, the nitriles of complex 2 are caged, and 2 does not act as a potent enzyme inhibitor. However, when 2 is irradiated, it releases 1, which inhibits the cysteine proteases papain and cathepsins B, K and L up to 2 times more potently than 1 alone. Ratios of the IC(50) values in the dark versus in the light ranged from 6:1 to 33:1 for inhibition by 2 against isolated enzymes and in human cell lysates, confirming that a high level of photoinduced enzyme inhibition can be obtained using this method.     

Synthesis,characterization, spectroscopic and theoretical studies of transition metal complexes of new nano Schiff base derived from l‐histidine and 2‐acetylferrocene and evaluation of biological and anticancer activities

A new Schiff base derived from the condensation of 2‐acetylferrocene with l ‐histidine was prepared and characterized using elemental analyses and spectroscopic methods. Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes of the Schiff base were prepared and characterized using various physicochemical methods such as elemental analysis, Fourier transform infrared and UV–visible spectroscopies, molar conductance, thermal analysis and scanning electron microscopy (SEM). Both ligand and complexes were investigated for their biological and anticancer activities. The elemental analyses showed that complexes were formed in a metal‐to‐ligand ratio of 1:1 stoichiometry. The spectral analyses proved that the ligand was tridentate and all complexes had an octahedral geometry, except the Zn(II) complex that was tetrahedral. SEM showed that the ligand and its Cd(II) complex were of nanometric structure. The molecular and electronic structure of the free ligand was optimized theoretically and the quantum chemical parameters were calculated. The molecular structure can be used to investigate the coordination sites and the total charge density around each atom. According to anticancer studies, Cd(II) complex was recommended to be used as anti‐breast cancer drug as it had very low IC₅₀ (3.5 μg ml^?1). Molecular docking was used to predict the binding between the free ligand and its Cd(II) complex and crystal structure of Staphylococcus aureus (PDB ID: 3Q8u), receptors of breast cancer mutant oxidoreductase (PDB ID: 3Hb5) and crystal structure of Escherichia coli (PDB ID: 3 T88) and to identify the binding mode and the crucial functional groups interacting with the three proteins.     

Inhibition of paraoxonase 1 by coumarin‐substituted N‐heterocyclic carbene silver(I), ruthenium(II) and palladium(II) complexes

We synthesized three coumarin‐substituted benzimidazolium chlorides and their silver(I), ruthenium(II) and palladium(II) N‐heterocyclic carbene (NHC) complexes. All compounds were characterized using appropriate spectroscopic techniques and elemental analyses. Single‐crystal X‐ray structure of a Pd(II)–NHC complex ( 6b ) was also determined. The inhibitory properties of all compounds were tested on the activity of human paraoxonase 1 (PON1). All complexes exhibited weaker inhibitory properties than their corresponding benzimidazolium salts except for complex 6b which is the most active inhibitor with an IC₅₀ value of 3.01 μM among the compounds reported in this study. A kinetic evaluation showed that this complex inhibits PON1 activity in a non‐competitive manner. Molecular docking studies were also performed for 6b in order to obtain more insight into the binding mode.     

Mutation scanning-coupled analysis of haplotypic variability in mitochondrial DNA regions reveals low gene flow between human and porcine Ascaris in endemic regions of China

Haplotypic variation within and among the Ascaris populations representing six provinces in China was investigated. Mitochondrial DNA regions in the cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 (nad1) genes were amplified by PCR from total genomic DNA samples (n > 720) from Ascaris individuals from humans and pigs, and subjected to mutation scanning and subsequent selective sequencing. For the cox1, ten different electrophoretic profiles were recorded for human Ascaris, and the same number for pig Ascaris, one of them being common to both host species. For the nad1, 11 different profiles were detected for human Ascaris, and 15 for pig Ascaris. Having defined all haplotypes (20 for pcox1 and 26 for pnad1) by sequencing, their frequencies were estimated in each of the two host species and each of the six provinces. For each mitochondrial region, the frequency of the different haplotypes varied considerably, depending on host species and geographical origin. Analysis of the sequence data (representing all haplotypes for each mitochondrial locus) by F-statistics indicated restricted gene flow between human Ascaris and pig Ascaris, and supported the conclusions from previous molecular epidemiological investigations that pigs are not a significant source of Ascaris infection in humans in endemic regions.     

Spectroscopic,electrochemical, theoretical characterization and biological evaluation of a ferrocenyl-substituted unsymmetric azine ligand and its Cu(II) complex

Ferrocenyl-substituted unsymmetrical azine and its Cu(II) complex were prepared. The redox active ferrocene-based azine was obtained by condensation of 1-[(E)-hydrazono]-5-bromo-2-hydroxybenzene with ferrocene carboxaldehyde. The ferrocenyl ligand and its Cu(II) complex were characterized by IR, UV–vis, NMR, X-ray, magnetic susceptibility, molar electrical conductivity measurements, and TG techniques. The redox behaviors of the ferrocene compounds were investigated by cyclic voltammetry. Structural parameters and spectroscopic properties of the ligand and the Cu(II) complex were calculated by employing density functional theory (DFT) and time-dependent DFT and compared with available experimental data. We found slightly stronger binding ability for Cu(II) complex than the free ligand. DNA binding abilities for ferrocenyl-substituted unsymmetrical azine ligand and its Cu(II) complex are higher than some reported ferrocene compounds. We also studied DNA cleavage, superoxide and DPPH radical scavenging abilities of the compounds. Furthermore, the synthesized organometallic compounds can be bound to DNA through an intercalative mode.     

Synthesis, magnetostructural correlation, and catalytic promiscuity of unsymmetric dinuclear copper(II) complexes: models for catechol oxidases and hydrolases

Herein, we report the synthesis and characterization, through elemental analysis, electronic spectroscopy, electrochemistry, potentiometric titration, electron paramagnetic resonance, and magnetochemistry, of two dinuclear copper(II) complexes, using the unsymmetrical ligands N',N',N-tris(2-pyridylmethyl)-N-(2-hydroxy-3,5-di-tert-butylbenzyl)-1,3-propanediamin-2-ol (L1) and N',N'-bis(2-pyridylmethyl)-N,N-(2-hydroxybenzyl)(2-hydroxy-3,5-di-tert-butylbenzyl)-1,3-propanediamin-2-ol (L2). The structures of the complexes [Cu(2)(L1)(μ-OAc)](ClO(4))(2)·(CH(3))(2)CHOH (1) and [Cu(2)(L2)(μ-OAc)](ClO(4))·H(2)O·(CH(3))(2)CHOH (2) were determined by X-ray crystallography. The complex [Cu(2)(L3)(μ-OAc)](2+) [3; L3 = N-(2-hydroxybenzyl)-N',N',N-tris(2-pyridylmethyl)-1,3-propanediamin-2-ol] was included in this study for comparison purposes only (Neves et al. Inorg. Chim. Acta2005, 358, 1807-1822). Magnetic data show that the Cu(II) centers in 1 and 2 are antiferromagnetically coupled and that the difference in the exchange coupling J found for these complexes (J = -4.3 cm(-1) for 1 and J = -40.0 cm(-1) for 2) is a function of the Cu-O-Cu bridging angle. In addition, 1 and 2 were tested as catalysts in the oxidation of the model substrate 3,5-di-tert-butylcatechol and can be considered as functional models for catechol oxidase. Because these complexes possess labile sites in their structures and in solution they have a potential nucleophile constituted by a terminal Cu(II)-bound hydroxo group, their activity toward hydrolysis of the model substrate 2,4-bis(dinitrophenyl)phosphate and DNA was also investigated. Double electrophilic activation of the phosphodiester by monodentate coordination to the Cu(II) center that contains the phenol group with tert-butyl substituents and hydrogen bonding of the protonated phenol with the phosphate O atom are proposed to increase the hydrolase activity (K(ass.) and k(cat.)) of 1 and 2 in comparison with that found for complex 3. In fact, complexes 1 and 2 show both oxidoreductase and hydrolase/nuclease activities and can thus be regarded as man-made models for studying catalytic promiscuity.     

Development of an reliable analytical method for synergistic extractive spectrophotometric determination of cobalt(II) from alloys and nano composite samples by using chromogenic chelating ligand

A synergistic simple and selective spectrophotometric method was developed for the determination of cobalt(II) with 1-(2',4'-dinitro aminophenyl)-4,4,6-trimethyl-1,4-dihydropyrimidine-2-thiol [2',4'-dinitro APTPT] as a chromogenic reagent. The proposed method has been described on the basis of synergistic effective extraction of cobalt(II) in presence of pyridine at pH range 9.5-10.2, showed orange-red coloured ternary complex having molar ratio 1:2:2 (M:L:Py). The equilibrium time is 10 min for extraction of cobalt(III) from organic phase. The absorbance of coloured organic layer in chloroform is measured spectrophotometrically at 490 nm against reagent blank. The Beer's law was obeyed in the concentration range 2.5-15 μg mL(-1) of cobalt(II) and optimum concentration range was 5-12.5 μg mL(-1) of cobalt(II) and it was evaluated from Ringbom's plot. The molar absorptivity and Sandell's sensitivity of cobalt(II)-2',4'-dinitro APTPT-pyridine complex in chloroform are 1.109×10(3) L mol(-1) cm(-1) and 0.053 μg cm(-2), respectively while molar absorptivity and Sandell's sensitivity of cobalt(II)-2',4'-dinitro APTPT complex in chloroform are 6.22×10(2) L mol(-1) cm(-1) and 0.096 μg cm(-2), respectively. The composition of cobalt(II)-2',4'-dinitro APTPT-pyridine complex (1:2:2) was established by slope ratio method, mole ratio method and Job's method of continuous variation. The ternary complex was stable for more than 48 h. The interfering effects of various cations and anions were also studied, and use of suitable masking agents enhances the selectivity of the method. The method is successfully applied for the determination of cobalt(II) in binary, synthetic mixtures and real samples. A repetition of the method was checked by finding relative standard deviation (R.S.D.) for n=5 which was 0.15%. The reliability of the method is confirmed by comparison of experimental results with atomic absorption spectrophotometer.     

Elucidation of the solution structure and water-exchange mechanism of paramagnetic [Fe(II)(edta)(H(2)O)](2-)

The lability and structural dynamics of [Fe(II)(edta)(H(2)O)](2-) (edta = ethylenediaminetetraacetate) in aqueous solution strongly depend on solvent interactions. To study the solution structure and water-exchange mechanism, (1)H, (13)C, and (17)O NMR techniques were applied. The water-exchange reaction was studied through the paramagnetic effect of the complex on the relaxation rate of the (17)O nucleus of the bulk water. In addition to variable-temperature experiments, high-pressure NMR techniques were applied to elucidate the intimate nature of the water-exchange mechanism. The water molecule in the seventh coordination site of the edta complex is strongly labilized, as shown by the water-exchange rate constant of (2.7 +/- 0.1) x 106 s(-1) at 298.2 K and ambient pressure. The activation parameters DeltaH(not equal), DeltaS(not equal), and DeltaV(not equal) were found to be 43.2 +/- 0.5 kJ mol(-1), +23 +/- 2 J K(-1) mol(-1), and +8.6 +/- 0.4 cm(3) mol(-1), respectively, in line with a dissociatively activated interchange (Id) mechanism. The scalar coupling constant (A/h) for the Fe(II)-O interaction was found to be 10.4 MHz, slightly larger than the value A/h = 9.4 MHz for this interaction in the hexa-aqua Fe(II) complex. The solution structure and dynamics of [Fe(II)(edta)(H(2)O)](2-) were clarified by (1)H and (13)C NMR experiments. The complex undergoes a Delta,Lambda-isomerization process with interconversion of in-plane (IP) and out-of-plane (OP) positions. Acetate scrambling was also found in an NMR study of the corresponding NO complex, [Fe(III)(edta)(NO(-))](2-).     

Synthesis and characterization of photoaffinity probe of acetogenin, a strong inhibitor of mitochondrial complex I

Acetogenins are valuable inhibitor probes to get an insight into the structural and functional properties of mitochondrial NADH-ubiquinone oxidoreductase (complex I). We synthesized a photoreactive acetogenin mimic ([¹²⁵I]DANA) which retained a strong inhibitory activity. The preliminary photoaffinity labeling with bovine heart submitochondrial particles revealed that [¹²⁵I]DANA binds to the ND1 subunit among 45 different subunits with high specificity.     

The metal complexes of some azo and azomethine dyestuffs : Determination of stability constants,and preparation of solid complexes

The stability constants of the complexes of 4-(2-pyridylazo)-resorcinol (I) with copper(II), cobalt-(II), zinc(Il), lead(ll), and uranium(VI) were determined by potentiometric titration in aqueous media, and were shown to have very high values, the stability constant of the copper(ll) complex approaching that of the copper(ll)-EDTA complex. The nickel(II) complex was shown to behave anomalously. The stability constants were also determined by this method in 1:1 dioxan/water, and the values obtained compared with those for the complexes of salicylidene-2-aminopyridine (II), 2-(o-hydroxy-phenyl-imino-methyl)-pyridine(III), and benzeneazoresorcino (IV). It is shown that chelation by (1) is terdentate, involving the pyridine nitrogen, the o-hydroxyl group and the azo nitrogen farthest from the heterocycle.The solid copper(II) complexes of these four ligands were prepared; in the solid complexes the azo nitrogen nearest the heterocycle plays a greater part than in the complexes in solution.     

Structural basis for bifunctional zinc(II) macrocyclic complex recognition of thymine bulges in DNA

The zinc(II) complex of 1-(4-quinoylyl)methyl-1,4,7,10-tetraazacyclododecane (cy4q) binds selectively to thymine bulges in DNA and to a uracil bulge in RNA. Binding constants are in the low-micromolar range for thymine bulges in the stems of hairpins, for a thymine bulge in a DNA duplex, and for a uracil bulge in an RNA hairpin. Binding studies of Zn(cy4q) to a series of hairpins containing thymine bulges with different flanking bases showed that the complex had a moderate selectivity for thymine bulges with neighboring purines. The dissociation constants of the most strongly bound Zn(cy4q)-DNA thymine bulge adducts were 100-fold tighter than similar sequences with fully complementary stems or than bulges containing cytosine, guanine, or adenine. In order to probe the role of the pendent group, three additional zinc(II) complexes containing 1,4,7,10-tetraazacyclododecane (cyclen) with aromatic pendent groups were studied for binding to DNA including 1-(2-quinolyl)methyl-1,4,7,10-tetraazacyclododecane (cy2q), 1-(4-biphenyl)methyl-1,4,7,10-tetraazacyclododecane (cybp), and 5-(1,4,7,10-tetraazacyclododecan-1-ylsulfonyl)-N,N-dimethylnaphthalen-1-amine (dsc). The Zn(cybp) complex binds with moderate affinity but little selectivity to DNA hairpins with thymine bulges and to DNA lacking bulges. Similarly, Zn(dsc) binds weakly both to thymine bulges and hairpins with fully complementary stems. The zinc(II) complex of cy2q has the 2-quinolyl moiety bound to the Zn(II) center, as shown by (1)H NMR spectroscopy and pH-potentiometric titrations. As a consequence, only weak (500 μM) binding is observed to DNA with no appreciable selectivity. An NMR structure of a thymine-bulge-containing hairpin shows that the thymine is extrahelical but rotated toward the major groove. NMR data for Zn(cy4q) bound to DNA containing a thymine bulge is consistent with binding of the zinc(II) complex to the thymine N3(-) and stacking of the quinoline on top of the thymine. The thymine-bulge bound zinc(II) complex is pointed into the major groove, and there are interactions with the guanine positioned 5' to the thymine bulge.     

A study on the mimics of Cu-Zn superoxide dismutase with high activity and stability: two copper(II) complexes of 1,4,7-triazacyclononane with benzimidazole groups

Two copper(II) complexes [CuL(1)Cl]ClO(4) and [CuL(2)MeCN](ClO(4))(2)xH(2)O were synthesized (L(1)= 1-(benzimidazole-2-ylmethyl)-1,4,7-triazacyclononane, L(2)= 1,4-bis(benzimidazole-2-ylmethyl)-1,4,7-triazacyclonone). The benzimidazole groups were N-substituents of tacn, and the complexes are more stable than their parents. They are able to catalyse the dismutation of superoxide anion in aqueous solutions at physiological pH and in bovine serum albumin solution (0.5 mg ml(-1)). X-ray structure analysis and EPR and electronic spectra show that the structure of complex is more similar to the Cu(II) centre of Cu(2)Zn(2)SOD than that. Comparing with other Cu(II) complexes, the complex possesses both high SOD activity and highly thermodynamic stability.     

4-(N,N-diethylamino) benzaldehyde thiosemicarbazone in the spectrophotometric determination of palladium

4-(N,N-diethylamino)benzaldehyde thiosemicarbazone(DEABT) is proposed as a sensitive and selective analytical reagent for the spectrophotometric determination of palladium(II). The reagent reacts with palladium (II) in a potassium hydrogen phthalate-hydrochloric acid buffer of pH 3.0, to form a yellow complex. Beer's law is obeyed in the concentration range up to 3.60 microgmL(-1). The optimum concentration range for minimum photometric error as determined by Ringbom plot method is 0.36 - 3.24 microg mL(-1). The yellow Pd(II)-DEABT complex shows a maximum absorbance at 408 nm, with molar absorptivity of 3.33 x 10(4) dm3 mol(-1) cm(-1) and Sandell's sensitivity of the complex from Beer's data, for D = 0.001, is 0.0032 microg cm(-2). The composition of the Pd(II)-DEABT complex is found to be 1:2 (M:L). The interference of various cations and anions in the method were studied. The proposed method was successfully used for the determination of Pd(II) in alloys, catalysts, complexes and model mixtures with a fair degree of accuracy.     

Structure-activity analysis of fluorinated 1-N-arylamino-1-arylmethane-phosphonic acid esters as inhibitors of the NADH:ubiquinone oxidoreductase (complex I)

Summary The structural and electronic properties of fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters were studied and related to the inhibitory effects on NADH:ubiquinone oxidoreductase (complex I). Electrostatic potential surfaces, dipole moments and molecular geometries were analysed. Based on the conformational analysis and the electronic parameters, a simple model for the active site of the fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters was developed, explaining the inhibitory power. The strongest inhibition effects were found for the 1-(N-4-trifluoromethoxyphenyl)-amino-1-phenylmethanephosphonic acid diethyl ester 1bab.     

New types of heterospin complexes from trans-oxamido-bridged copper(II) binuclear units and nitronyl nitroxide radicals: crystal structure and magnetic characterization

Three new heterospin complexes derived from trans-oxamido-bridged copper(II) binuclear units [Cu(2)(oxen), oxen = N,N-bis(2-aminoethyl)oxamide] and pyridine-substituted nitronyl nitroxides (o-, m-, and p-PYNN) were synthesized and characterized structurally and magnetically. Complexes 1 and 2 are four-spin complexes. Interestingly, it is found that in complex 3, the Cu(II) ions and m-PYNN units are arranged to form 1D double-stranded helical chains, which to the best of our knowledge is the first example of a metal nitronyl nitroxide complex with such a 1D helical structure. The temperature dependencies of the magnetic susceptibilities of 1 and 2 were fitted to the four-spin model with the Hamiltonian H = -2Js(Cu1)s(Cu2) - 2j(s(Cu1)s(rad1) - s(Cu2)s(rad2)), leading to J = -150.5 cm(-)(1) and j = 47.2 cm(-)(1) for complex 1 and J = -191.7 cm(-)(1) and j = -18.9 cm(-)(1) for complex 2. The temperature dependence of the magnetic susceptibility of complex 3 was approximately simulated with a simple model composed of a dimer of Cu(II) ions and two m-PYNN molecules. The best fitting leads to the values of J = -183.0 cm(-)(1) and zJ' = -0.55 cm(-)(1) for the magnetic exchange of two Cu(II) ions through the oxamide bridge and that between the dimer of Cu(II) ions and two m-PYNN molecules, respectively. The antiferromagnetic exchange of oxamido-bridged Cu(II) ions in complexes 1-3 is strong. The strength of such antiferromagnetic interactions is also similar for the three complexes.     

Geometry-dependent phosphodiester hydrolysis catalyzed by binuclear copper complexes

Two isomeric binuclear ligands PBTPA and MBTPA and their copper(II) complexes were prepared and examined for hydrolysis of a model phosphodiester substrate: bis(p-nitrophenyl)phosphate. A bell-shaped pH vs rate profile, which is in agreement with one mechanism proposed for bimetallonucleases/phosphatases, was observed for the binuclear complex of copper(II) and PBTPA. At pH 8.4, a maximum rate of 1.14 x 10(-6) s(-1)--more than 10(4)-fold over uncatalyzed reactions--was achieved. However, the analogous complex of MBTPA did not show significant rate enhancement. The binuclear complex of copper(II) and PBTPA also showed 10-fold acceleration over mononuclear complex of copper(II) and tris(2-pyridylmethyl)amine (TPA) catalyzed reaction. A phage phiX174 DNA assay showed that the complex of copper(II) and PBTPA promoted supercoiled phage phiX174 DNA relaxation under both aerobic and anaerobic conditions, in contrast to the hydrolytic inactivity of the mononuclear complex of copper(II) and TPA.     

Univariate and simplex optimization for the flow-injection spectrophotometric determination of copper using nitroso-R salt as a complexing agent.

A simple colorimetric flow-injection system for the determination of Cu(II) based on a complexation reaction with nitroso-R salt is described. The chemical and FIA variables were established using the univariate and simplex methods. A small volume of Cu(II) was mixed with merged streams of nitroso-R salt and acetate buffer solutions. The absorbance of the complex was continuously monitored at 492 nm. The calibration curve over the concentration range 1.0-7.0 microg ml(-1) was obtained. The relative standard deviation for determining 4.0 microg ml(-1) Cu(II) was 0.47% (n = 11). The detection limit (3sigma) was 0.68 microg ml(-1) and the sample throughput was 150 h(-1). The validity of the method has been satisfactorily examined for the determination of Cu(II) in wastewater and copper ore samples. The accuracy was found to be high, because the student t-values were calculated to be less than the theoretical values when the results were compared with those obtained by FAAS.