New La(III) complex immobilized on 3-aminopropyl-functionalized silica as an efficient and reusable catalyst for hydrolysis of phosphate ester bonds.

Described herein is the synthesis, structure, and monoesterase and diesterase activities of a new mononuclear [La(III)(L(1))(NO3)2] (1) complex (H2L(1) = 2-bis[{(2-pyridylmethyl)-aminomethyl}-6-[N-(2-pyridylmethyl) aminomethyl)])-4-methyl-6-formylphenol) in the hydrolysis of 2,4-bis(dinitrophenyl)phosphate (2,4-BDNPP). When covalently linked to 3-aminopropyl-functionalized silica, 1 undergoes disproportionation to form a dinuclear species (APS-1), whose catalytic efficiency is increased when compared to the homogeneous reaction due to second coordination sphere effects which increase the substrate to complex association constant. The anchored catalyst APS-1 can be recovered and reused for subsequent hydrolysis reactions (five times) with only a slight loss in activity. In the presence of DNA, we suggest that 1 is also converted into the dinuclear active species as observed with APS-1, and both were shown to be efficient in DNA cleavage.

Ratiometric Electrochemical Sensor for Butralin Determination Using a Quinazoline-Engineered Prussian Blue Analogue.

A ratiometric electrochemical sensor based on a carbon paste electrode modified with quinazoline-engineered ZnFe Prussian blue analogue (PBA-qnz) was developed for the determination of herbicide butralin. The PBA-qnz was synthesized by mixing an excess aqueous solution of zinc chloride with an aqueous solution of precursor sodium pentacyanido(quinazoline)ferrate. The PBA-qnz was characterized by spectroscopic and electrochemical techniques. The stable signal of PBA-qnz at +0.15 V vs. Ag/AgCl, referring to the reduction of iron ions, was used as an internal reference for the ratiometric sensor, which minimized deviations among multiple assays and improved the precision of the method. Furthermore, the PBA-qnz-based sensor provided higher current responses for butralin compared to the bare carbon paste electrode. The calibration plot for butralin was obtained by square wave voltammetry in the range of 0.5 to 30.0 µmol L-1, with a limit of detection of 0.17 µmol L-1. The ratiometric sensor showed excellent precision and accuracy and was applied to determine butralin in lettuce and potato samples.

Synthesis, characterization and cytotoxicity of copper (II) complex containing a 2H-benzo[e][1,3]oxazin derivative.

A new cis-dihalo copper(II) complex, [CuII(HLbz)(Cl)2].CH3CN (1), where HLbz = (S)-2-(((2-(2-(pyridin-2-yl)-2H-benzo[e][1,3]oxazin-3(4H)-yl)ethyl)amino)methyl)phenol), was isolated by reacting copper(II) chloride dihydrate and the H2L ligand (H2L = 2,2'-((2-(pyridin-2-yl)imidazolidine-1,3-diyl)bis(methylene))diphenol) in a MeOH/CH3CN (1:3 v/v) mixture. The complex formation occurred via the ligand modification during complexation, producing a unique structure containing 2H-benzo[e][1,3]oxazin, as observed from the single crystal X-ray structure determination. The complex was characterized by elemental analysis, potentiometric titration, spectroscopic techniques (UV-Vis, FT-IR) and conductance measurements. Complex 1 inhibits the growth of myelogenous leukemia cells with an IC50 of 17.3 µmol L-1.

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.

New AlIIIZnII and AlIIICuII dinuclear complexes: Phosphatase-like activity and cytotoxicity.

Herein, we report the synthesis and characterization of the first two AlIII(µ-OH)MII (M = Zn (1) and Cu (2)) complexes with the unsymmetrical ligand H2L{2-[[(2-hydroxybenzyl)(2-pyridylmethyl)]aminomethyl]-6-bis(pyridylmethyl)aminomethyl}-4-methylphenol. The complexes were characterized through elemental analysis, X-ray crystallography, IR spectroscopy, mass spectrometry and potentiometric titration. In addition, complex 2 was characterized by electronic spectroscopy. Kinetics studies on the hydrolysis of the model substrate bis(2,4-dinitrophenyl)phosphate by 1 and 2 show Michaelis-Menten behavior, with 1 being slightly more active (8.31%) than 2 (at pH 7.0). The antimicrobial effect of the compounds was studied using four bacterial strains (Staphylococcus aureus, Pseudomonas aeuruginosa, Shigella sonnei and Shigella dysenteriae) and for both complexes the inhibition of bacterial growth was superior to that caused by sulfapyridine, but inferior to that of tetracycline. The dark cytotoxicity and photocytotoxicity (under UV-A light) of the complexes in a chronic myelogenous leukemia cell line were investigated. Complexes 1 and 2 exhibited significant cytotoxic activity against K562 cells, which undergoes a 2-fold increase on applying 5 min of irradiation with UV-A light. Complex 2 was more effective and a good correlation between cytotoxicity and intracellular concentration was observed, the intracellular copper concentration required to inhibit 50% of cell growth being 3.5 × 10-15 mol cell-1.

Synthesis, structure, and phosphatase-like activity of a new trinuclear Gd complex with the unsymmetrical ligand H3L as a model for nucleases.

The new trinuclear gadolinium complex [Gd(3)L(2)(NO(3))(2)(H(2)O)(4)]NO(3).8H(2)O (1) with the unsymmetrical ligand 2-[N-bis-(2-pyridylmethyl)aminomethyl]-4-methyl-6-[N-bis(2-hydroxy-2-oxoethyl)aminomethyl] phenol (H(3)L) was synthesized and characterized. The new ligand H(3)L was obtained in good yield. Complex 1 crystallizes in an orthorhombic cell, space group Pcab. Kinetic studies show that complex 1 is highly active in the hydrolysis of the substrate 2,4-bis(dinitrophenyl)phosphate (K(m) = 4.09 mM, V(max) = 2.68 x 10(-2) mM s(-1), and k(cat) = V(max)/[1] = 0.67 s(-1)). Through a potentiometric study and determination of the kinetic behavior of 1 in acetonitrile/water solution, the species present in solution could be identified, and a trinuclear monohydroxo species appears to be the most prominent catalyst under mild conditions. Complex 1 displays high efficiency in DNA hydrolytic cleavage, and complete kinetic studies were carried out (K(m) = 4.57 x 10(-4) M, k'(cat) = 3.42 h(-1), and k'(cat)/K(m) = 7.48 x 10(3) M(-1) h(-1)). Studies with a radical scavenger (dimethyl sulfoxide, DMSO) showed that it did not inhibit the activity, indicating the hydrolytic action of 1 in the cleavage of DNA, and studies on the incubation of distamycin with plasmid DNA suggest that 1 is regio-specific, interacting with the minor groove of DNA.

Efficient phosphodiester hydrolysis by luminescent terbium(III) and europium(III) complexes.

The synthesis and structures of two new isostructural mononuclear [Ln(L)(NO(3))(H(2)O)(3)](NO(3))(2) complexes, with Ln = Tb (complex 1) and Eu (complex 2), which display high activity in the hydrolysis of the substrate 2,4-bis(dinitrophenyl)phosphate, are reported. These complexes displayed catalytic behavior similar to the mononuclear gadolinium complex [Gd(L)(NO(3))(H(2)O)(3)](NO(3))(2) previously reported by us (Inorg. Chem. 2008, 47, 2919-2921); one hydrolysis reaction in two stages where the diesterase and monoesterase activities could be monitored separately, with the first stage dependent on and the second independent of the complex concentration. Through potentiometric studies, electrospray ionization mass spectrometry (ESI-MS) analysis, and determination of the kinetic behaviors of 1 and 2 in acetonitrile/water solution, the species present in solution could be identified and suggested a dinuclear species, with one hydroxo group, as the most prominent catalyst under mild conditions. The complexes show high activity (k(1) = 7 and 18 s(-1) for 1 and 2, respectively) and catalytic efficiency. Complexes 1 and 2 were found to be active toward the cleavage of plasmid DNA, and complete kinetic studies were carried out. Studies with a radical scavenger (dimethylsulfoxide) confirmed the hydrolytic action of 1 and 2 in the cleavage of DNA. Studies on the incubation of distamycin with plasmid DNA suggested that 1 and 2 are regio-specific, interacting with the minor groove of DNA. These complexes displayed luminescent properties. Complex 1 showed higher emission intensity than 2 due to a more efficient energy transfer between triplet and emission levels of terbium (T --> (5)D(4)), along with nonradiative deactivation mechanisms of the excited states of europium via multiphonon decays and the ligand-to-metal charge transfer state. Lifetime measurements of the (5)D(4) and (5)D(0) excited levels for 1 and 2, respectively, indicated the numbers of coordinated water molecules for the complexes.

Transbuccal delivery of metal complexes of isoniazid as an alternative to overcome antimicrobial resistance problems.

In isolated isoniazid (INH)-resistant strains, deletion or mutations in thekatGgene have been identified, which result in loss of catalase-peroxidase activity. This enzyme plays a key role in the activation of this prodrug. As an alternative, the coordination of the INH to metal complexes has been purposed to activate it regardless of enzyme functionality. Although pentacyanido(isoniazid)ferrate(II) complexes have shown to be effective against resistant strains of Mycobacterium tuberculosis, low oral bioavailability was found. In this context, buccal mucosa was selected as an alternative route to the metal complex delivery. Moreover, oral manifestations of tuberculosis(TB) have been observed in some patients, particularly when resistant strains are present, and no therapeutic options are currently available on the market. Pentacyanidoferrate (PCF-INH) and Prussian-blue (PB-INH) complexes were initially prepared and characterized, followed by buccal permeability studies in Franz-type diffusion cells. The electrochemical potential of the complexes demonstrated their ability to self-activate. Job's method suggested the presence of structural defects in PB-INH complexes, which was correlated with permeability results. In fact, PB-INH showed a higher dissociation rate in salt-rich aqueous medium and thus a high transport rate of INH through the buccal mucosa. Its passage through the tissue would not be possible due to the high molecular size. PCF-INH, in turn, presented a lower dissociation rate in the salt-rich aqueous medium, justifying its slower transport rate through the tissue. Taken together, these results suggest that INH-based metal complexes may be efficiently administered through the buccal route, impacting on both oral bioavailability and microbial resistance.

Potentiometric titration of microhydrolysis products of oils: A new low-cost methodology and investment for the analysis of oil binders present in works of art.

The analysis of oil paints present in historical paintings is commonly carried out for research, authenticity and forensic purposes. This paper proposes potentiometric titration and calculation of the fatty acids concentrations with the aid of the Best7 program as an alternative technique to characterize the oil binders used in works of art. The method involves determining the ratio between the levels of palmitic (P) and stearic (S) acids present in the microhydrolysis products of commercial oil binders and paints. The microhydrolysis products were characterized, using FTIR spectroscopy, by displacement of the carbonyl band and the pKa values for the C16 and C18 in the system studied were determined. The P/S ratios found for the microhydrolysis products of linseed, palm and nut oils were 1.65, 5.91 and 2.42, respectively. For the commercial paints analyzed, values ranging from 1.34 to 1.98 were obtained, characterizing the presence of linseed oil. The values were confirmed by GC-MS and are in agreement with those reported in the literature for the oils investigated in this study.

Unsymmetrical Fe(III)Co(II) and Ga(III)Co(II) complexes as chemical hydrolases: biomimetic models for purple acid phosphatases (PAPs).

The design and development of suitable biomimetic catalytic systems capable of mimicking the functional properties of enzymes continues to be a challenge for bioinorganic chemists. In this study, we report on the synthesis, X-ray structures, and physicochemical characterization of the novel isostructural [Fe(III)Co(II)(BPBPMP)(mu-OAc)(2)]ClO(4) (1) and [Ga(III)Co(II)(BPBPMP)(mu-OAc)(2)]ClO(4) (2) complexes with the unsymmetrical dinucleating ligand H(2)BPBPMP (2-bis[{(2-pyridyl-methyl)-aminomethyl}-6-{(2-hydroxy-benzyl)-(2-pyridyl-methyl)}-aminomethyl]-4-methylphenol). The previously reported complex [Fe(III)Zn(II)(BPBPMP)(mu-OAc)(2)]ClO(4) (3) was investigated here by electron paramagnetic resonance for comparison with such studies on 1 and 2. A magneto-structural correlation between the exchange parameter J (cm(-1)) and the average bond lengh d (A) of the [Fe(III)-O-M(II)] structural unit for 1 and for related isostructural Fe(III)M(II) complexes using the correlation J = -10(7) exp(-6.8d) reveals that this parameter is the major factor that determines the degree of antiferromagnetic coupling in the series [(BPBPMP)Fe(III)(mu-OAc)(2)M(II)](+) (M(II) = Mn, Fe, Co, Ni) of complexes. Potentiometric and spectrophotometric titrations along with electronic absorption studies show that, in aqueous solution, complexes 1 and 2 generate the [(HO)M(III)(mu-OH)Co(II)(H(2)O)] complex as the catalytically active species in diester hydrolysis reactions. Kinetic studies on the hydrolysis of the model substrate bis(2,4-dinitrophenyl)phosphate by 1 and 2 show Michaelis-Menten behavior, with 2 being 35% more active than 1. In combination with k(H)/k(D) isotope effects, the kinetic studies suggest a mechanism in which a terminal M(III)-bound hydroxide is the hydrolysis-initiating nucleophilic catalyst. In addition, the complexes show maximum catalytic activity in DNA hydrolysis near physiological pH. The modest reactivity difference between 1 and 2 is consistent with the slightly increased nucleophilic character of the Ga(III)-OH terminal group in comparison to Fe(III)-OH in the dinuclear M(III)Co(II) species.

Effect of surface and porosity of biochar on water holding capacity aiming indirectly at preservation of the Amazon biome.

As part of efforts to reduce pressure on the Amazon and other biomes, one approach considered by Brazilian authorities and scientists is more intensive use of the soils of the interior of the northeast of the country, which are generally sandy, with low contents of organic matter and low water holding capacity and are frequently affected by severe droughts. In this work, biochars produced from waste biomasses were tested for the improvement of these soils. The highest BET (Brunauer-Emmett-Teller) specific surface areas were observed for all biochars. In the pH range studied, the water hyacinth plants (WH) sample showed the most negative zeta potentials, as well as the highest water holding capacity (WHC) values, while the zeta potentials of two quartzarenic neosol soils were consistent with their WHC values. The results suggested that despite the effect of porosity on water retention, the zeta potential could be associated with the presence of negative charges by which hydrated cationic counterions were absorbed and retained. The surface energy and its polar and dispersive components were associated with water retention, with sugar cane bagasse, orange peel, and water hyacinth biochars presenting higher SE values and larger polar components.

Synthesis, X-ray structure and antimycobacterial activity of silver complexes with alpha-hydroxycarboxylic acids.

In this paper, synthesis, characterization and antimycobacterial properties of a new water-soluble complex identified as silver-mandelate are described. Elemental and thermal analyses are consistent with the formula [Ag(C(6)H(5)C(OH)COO)](n). The polymeric structure was determined by single X-ray diffraction and the two-dimensional structure is based on the bis(carboxylate-O,O') dimer [Ag-O, 2.237(3), 2.222(3) Angstrom]. The structure is extended along both the b and c axes through two oxygen atoms of a bidentate alpha-hydroxyl-carboxylate residue [Ag-OH(hydroxyl), 2.477(3) Angstrom; Ag-O(carboxylate), 2.502(3) Angstrom; O-Ag-O, 63.94(9) degrees]. A strong d(10)-d(10) interaction was observed between two silver atoms. The Ag - Ag distance is 2.8307(15) Angstrom. The NMR (13)C spectrum in D(2)O shows that coordination of the ligand to Ag(I) occurs through the carboxylate group in solution. Potentiometric titration shows that only species with a molar metal:ligand ratio of 2:2 are formed in aqueous solution. The mandelate complex and the silver-glycolate, silver-malate and silver-hydrogen-tartarate complexes were tested against three types of mycobacteria, Mycobacterium avium, Mycobacterium tuberculosis and Mycobacterium kansasii, and their minimal inhibitory concentration (MIC) values were determined. The results show that the four complexes are potential candidates for antiseptic or disinfectant drugs for discharged secretions of patients affected with tuberculosis.

Effect of crude extract and fractions from Vitex megapotamica leaves on hyperglycemia in alloxan-diabetic rats.

The effect of the crude extract, ethyl acetate and n-butanol fractions from Vitex megapotamica (Spreng) Moldenke on glycemia was investigated in diabetic rats. Oral administration of crude extract significantly reduced serum glucose levels in both normal and diabetic animals. In normal rats, serum glucose lowering was observed with 400 and 800 mg/kg at 2 and 2-3h, respectively after oral crude extract treatment. Nevertheless, the hypoglycemic effect of Vitex megapotamica in diabetic rats was evident at 1 and 2h and from 1 to 3h after treatment with 400 and 800 mg/kg, respectively. The ethyl acetate as well as n-butanol fractions were able to diminish glycemia in diabetic animals. The ethyl acetate fraction (400 and 800 mg/kg) produced the maximum hypoglycemic effect (28 and 20%, respectively) in diabetic rats and the same dose of the n-butanol fraction reduced the hyperglycemia only by 11% at 1h after treatment. Additionally, in hyperglycemic normal rats neither crude extract nor ethyl acetate fraction modified the glucose tolerance and the known tolbutamide effect on insulin release was clearly observed in this group. Thus, this study shows that Vitex megapotamica has an anti-hyperglycemic action, is able to ameliorate the diabetic state and, probably, is a source of hypoglycemic compounds.

New unsymmetric dinuclear Cu(II)Cu(II) complexes and their relevance to copper(II) containing metalloenzymes and DNA cleavage.

The new homodinuclear complexes, [Cu(2)(II)(HLdtb)(mu-OCH(3))](ClO(4))(2) (1) and [Cu(2)(II)(Ldtb)(mu-OCH(3))](BPh(4)) (2), with the unsymmetrical N(5)O(2) donor ligand (H(2)Ldtb) - {2-[N,N-Bis(2-pyridylmethyl)aminomethyl]-6-[N',N'-(3,5-di-tert-butylbenzyl-2-hydroxy)(2-pyridylmethyl)]aminomethyl}-4-methylphenol have been synthesized and characterized in the solid state by X-ray crystallography. In both cases the structure reveals that the complexes have a common {Cu(II)(mu-phenoxo)(mu-OCH(3))Cu(II)} structural unit. Magnetic susceptibility studies of 1 and 2 reveal J values of -38.3 cm(-1) and -2.02 cm(-1), respectively, and that the degree of antiferromagnetic coupling is strongly dependent on the coordination geometries of the copper centers within the dinuclear {Cu(II)(mu-OCH(3))(mu-phenolate)Cu(II)} structural unit. Solution studies in dichloromethane, using UV-Visible spectroscopy and electrochemistry, indicate that under these experimental conditions the first coordination spheres of the Cu(II) centers are maintained as observed in the solid state structures, and that both forms can be brought into equilibrium ([Cu(2)(HLdtb)(mu-OCH(3))](2+)=[Cu(2)(Ldtb)(mu-OCH(3))](+)+H(+)) by adjusting the pH with Et(3)N (Ldtb(2-) is the deprotonated form of the ligand). On the other hand, potentiometric titration studies of 1 in an ethanol/water mixture (70:30 V/V; I=0.1M KCl) show three titrable protons, indicating the dissociation of the bridging CH(3)O(-) group.The catecholase activity of 1 and 2 in methanol/water buffer (30:1 V/V) demonstrates that the deprotonated form is the active species in the oxidation of 3,5-di-tert-butylcatechol and that the reaction follows Michaelis-Menten behavior with k(cat)=5.33 x 10(-3)s(-1) and K(M)=3.96 x 10(-3)M. Interestingly, 2 can be electrochemically oxidized with E(1/2)=0.27 V vs.Fc(+)/Fc (Fc(+)/Fc is the redox pair ferrocinium/ferrocene), a redox potential which is believed to be related to the formation of a phenoxyl radical. Since these complexes are redox active species, we analyzed their activity toward the nucleic acid DNA, a macromolecule prone to oxidative damage. Interestingly these complexes promoted DNA cleavage following an oxygen dependent pathway.

Follow-up studies on glycosylated flavonoids and their complexes with vanadium: their anti-hyperglycemic potential role in diabetes.

The present study sought to evaluate the hypoglycemic activities of free glycosylated flavonoids and flavonoid complexes with vanadium(IV), (VO(IV)), on glycemia in experimental diabetic rats. Besides free kaempferol-3,7-O-(alpha)-dirhamnoside and kaempferol-3-neohesperidoside, complexes of these flavonoids with VO(IV) were administered by different routes in order to compare the potency of the compounds as well as the efficacy of insulin or VO(IV) in lowering serum glucose. Wistar rats were made diabetic by alloxan. The glycemia was assessed at different times after the administering of compounds. The equilibrium constants were determined by potentiometric study and two species with VO(IV) are proposed at physiological pH, VOH(2)L(2) for kaempferitrin and VOHL for kaempferol-3-neohesperidoside. The latter exhibited hypoglycemic activity at all times examined with 50 and 100 mg/kg and the former reduced the glycemia from 0 to 6h by i.p. route. The administering of the complexes or 0.0146 mmol/kg VO(IV) resulted in a serum glucose-lowering effect over time in the case of i.p. treatment. A marked hypoglycemic effect was observed for 0.5IU of insulin (67.5%); 0.0146 mmol VO(IV) (16.8%); 0.0294 mmol kaempferitrin-VO(IV) (17.8%) and 0.0286 mmol kaempferol-3-neohesperidoside-VO(IV) (56.0%) at 3h after i.p. treatment when compared with respective zero time in diabetic groups. Kaempferol-3-neohesperidoside-VO(IV) was 2.5 times more effective than VO(IV), twice as effective as the free compound and three times more effective than kaempferitrin-VO(IV). This is of particular interest since kaempferol-3-neohesperidoside appears to represent a suitable ligand for VO(IV) to mimic the efficacy of insulin in lowering serum glucose levels.

Dopamine polymerization promoted by a catecholase biomimetic CuII(µ-OH)CuII complex containing a triazine-based ligand.

We describe herein the catecholase-like catalytic activity and dopamine polymerization by using a dinuclear [LCuII(µ-OH)2CuII](ClO4)2 (1) complex where L is the dinucleating triazine-based ligand 6-chloro-N2,N2,N4,N4-tetrakis(pyridin-2-ylmethyl)-1,3,5-triazine-2,4-diamine. The kinetic parameters (kcat = 0.318 s-1, KM = 1.6 × 10-3 mol L-1, and kcat/KM = 198.8 L s-1 mol-1), mechanistic insights into the oxidation of 3,5-di-tert-butyl catechol and early characterization of poly(dopamine) are presented.

Synthesis, crystal structure and investigation of mononuclear copper(II) and zinc(II) complexes of a new carboxylate rich tripodal ligand and their interaction with carbohydrates in alkaline aqueous solution.

A new carboxylate rich asymmetric tripodal ligand, N-[2-carboxybenzomethyl]-N-[carboxymethyl]-ß-alanine (H3camb), and its di-copper(II), (NH4)2[1]2, and di-zinc(II), ((CH3)4N)2[2]2, complexes have been synthesized as carbohydrate binding models in aqueous solutions. The ligand and complexes have been fully characterized using several techniques, including single crystal X-ray diffraction. The interactions of (NH4)2[1]2 and ((CH3)4N)2[2]2 with D-glucose, D-mannose, D-xylose and xylitol in aqueous alkaline media were investigated using UV-Vis and (13)C-NMR spectroscopic techniques, respectively. The molar conductance, NMR and ESI-MS studies indicate that the complexes dissociate in solution to produce the respective complex anions, 1(-) and 2(-). Complexes 1(-) and 2(-) showed chelating ability towards the naturally abundant and biologically relevant sugars, D-glucose, D-mannose, D-xylose, and xylitol. The complex ions bind to one molar equivalent of the sugars, even in the presence of stoichiometric excess of the substrates, in solution. Experimentally obtained spectroscopic data and computational results suggest that the substrates bind to the metal center in a bidentate fashion. Apparent binding constant values, pK(app), between the complexes and the substrates were determined and a specific mode of substrate binding is proposed. The pK(app) and relativistic density functional theory (DFT) calculated Gibbs free energy values indicate that D-mannose displayed the strongest interaction with the complexes. Syntheses, characterizations, detailed substrate binding studies using spectroscopic techniques, single crystal X-ray diffraction and geometry optimizations of the complex-substrates with DFT calculations are also reported.

Pheomelanin-coated iron oxide magnetic nanoparticles: a promising candidate for negative T2 contrast enhancement in magnetic resonance imaging.

We describe herein a novel type of monodisperse water-soluble magnetite nanoparticle coated with pheomelanin using an environmentally-friendly approach in aqueous medium. The results indicate superparamagnetic behaviour at room temperature and show improved negative contrast in T2-weighted MRI with a transverse relaxivity of 218 mM(-1) s(-1).

Induction of apoptosis in leukemia cell lines by new copper(II) complexes containing naphthyl groups via interaction with death receptors.

The synthesis, physico-chemical characterization and cytotoxicity of four new ligands and their respective copper(II) complexes toward two human leukemia cell lines (THP-1 and U937) are reported (i.e. [(HL1)Cu(µ-Cl)2Cu(HL1)]Cl2·H2O (1), [(H2L2)Cu(µ-Cl)2Cu(H2L2)]Cl2·5H2O (2), [(HL3)Cu(µ-Cl)2Cu(HL3)]Cl2·4H2O (3), [(H2L4)Cu(µ-Cl)2Cu(H2L4)]Cl2·6H2O (4)). Ligands HL1 and HL3 contain two pyridines, amine and alcohol moieties with a naphthyl pendant unit yielding a N3O coordination metal environment. Ligands H2L2 and H2L4 have pyridine, phenol, amine and alcohol groups with a naphthyl pendant unit providing a N2O2 coordination metal environment. These compounds are likely to be dinuclear in the solid state but form mononuclear species in solution. The complexes have an antiproliferative effect against both leukemia cell lines; complex (2) exhibits higher activity than cisplatin against U937 (8.20 vs 16.25µmoldm(-3)) and a comparable one against THP-1. These human neoplastic cells are also more susceptible than peripheral blood mononuclear cells (PBMCs) toward the tested compounds. Using C57BL/6 mice an LD50 of 55mgkg(-1) was determined for complex (2), suggesting that this compound is almost four times less toxic than cisplatin (LD50=14.5mgkg(-1)). The mechanism of cell death promoted by ligand H2L2 and by complexes (2) and (4) was investigated by a range of techniques demonstrating that the apoptosis signal triggered at least by complex (2) starts from an extrinsic pathway involving the activation of caspases 4 and 8. This signal is amplified by mitochondria with the concomitant release of cytochrome c and the activation of caspase 9.

Metal binding by melanins: studies of colloidal dihydroxyindole-melanin, and its complexation by Cu(II) and Zn(II) ions.

Melanins are colloidal pigments known to have a high affinity for metal ions. In this work, the nature of the metal-binding sites are determined and the binding affinities are quantified. Initial potentiometric titrations have been performed on synthetic dihydroxyindole (DHI) melanin solutions to determine the chemical speciation of quinole/quinone subunits. Two types of acidic functionalities are assignable: catechol groups, with pK(a) between 9 and 13, and quinone imines (QI), with pK(a) of 6.3. The presence of the quinone-imine tautomer has, to our knowledge, never been assessed in polymeric melanins. Melanin solutions obtained from N-methylated DHI lack the pK(a) 6.3 buffer, consistent with its inability to form the quinone-imine tautomer. EPR spectroscopy of the DHI-melanin samples demonstrates that the semiquinone radical is in too low a concentration to contribute to the bulk binding of metals. Changes in the titration curves after addition of Cu(II) and Zn(II) ions were analyzed to obtain the binding constants and stoichiometry of the metal-melanin complexes, using the BEST7 program. UV-Vis spectra at neutral and high pH are used to identify absorbances due to Cu-bound quinone imine and catechol groups. The derived binding constants were used to determine speciation of the Cu(II) and Zn(II) ions coordinated to the quinone imine and catechol groups at various pH. The mixed complexes, Zn(QI)(Cat)(-) and Cu(QI)(Cat)(-) are shown to dominate at physiological pH.