Kinetic study of ruthenium(III)-catalyzed oxidation of <Emphasis Type="SmallCaps">l</Emphasis>-alanine by diperiodatoargentate(III) in aqueous alkaline medium

The kinetics of Ru(III)-catalyzed oxidation of l-alanine (Ala) by diperiodatoargentate(III) (DPA) in alkaline medium at 25 °C and a constant ionic strength of 0.90 mol dm⁻³ was studied spectrophotometrically. The products are acetaldehyde, Ag(I), ammonia and bicarbonate. The [Ala] to [DPA] stoichiometry is 1:1. The reaction is first order in both [Ru(III)] and [DPA] and has less than unit order in both [Ala] and [alkali]. Addition of periodate has a retarding effect on the reaction. The effects of added products, ionic strength and dielectric constant of the reaction medium have been investigated. The reaction proceeds via a Ru(III)–Ala complex, which further reacts with one molecule of monoperiodatoargentate(III) in the rate-determining step. The reaction constants were calculated at different temperatures and the activation parameters have been evaluated.     

Investigation of the mechanism of oxidation of <Emphasis Type="SmallCaps">l</Emphasis>-cystine by diperiodatoargentate(III) in aqueous alkaline medium by stopped flow technique

The kinetics of oxidation of l-cystine by diperiodatoargentate(III) (DPA) in alkaline medium at a constant ionic strength of 0.10 mol dm⁻³ was studied spectrophotometrically. The reaction exhibits a 1:2 stoichiometry (l-cys:DPA) and is first order in [DPA]. The order in both [l-cystine] and [alkali] changes from first to zero order as their concentrations increase. Added periodate retards the rate of reaction. The effects of added products have been investigated. The active species of silver(III) is identified as monoperiodatoargentate(III) (MPA). The oxidation is thought to proceed via an MPA–l-cystine complex, which decomposes in a rate-determining step to give a free radical followed by a fast step to give the products. The products were identified by spot test, IR and GC–MS. The reaction constants involved in different steps of the mechanism were evaluated. The activation parameters with respect to the slow step of the mechanism were computed and discussed.     

Optical enzyme sensor for determining <Emphasis Type="SmallCaps">l</Emphasis>-lysine content using <Emphasis Type="SmallCaps">l</Emphasis>-lysine oxidase from the rockfish <Emphasis Type="BoldItalic">Sebastes schlegeli</Emphasis>

l-Lysine (l-Lys) in living bodies is critical for metabolism; therefore, determination of its levels in food is important. Most enzymatic methods for l-Lys analysis are performed using l-lysine oxidase (LyOx), but commercially manufactured LyOx is generally not highly selective for l-Lys among amino acids. We previously isolated LyOx as an antibacterial protein secreted from the skin of the rockfish Sebastes schlegeli. In the present study, we developed an optical enzyme sensor system for rapid and continuous determination of l-Lys using this LyOx. The system comprised an immobilized LyOx membrane, an optical oxygen probe, a flow system, and a personal computer. The amount of l-Lys was detected as a decrease in the oxygen concentration due to the LyOx reaction. The specificity of the sensor was examined against various amino acids. The sensor response was specific for l-Lys. Good reproducibility was obtained in 58 assays. The response of the sensor using commercially prepared LyOx was unstable compared with the response using LyOx isolated in our laboratory. Our sensor system could be used for 5 weeks without our having to change the enzyme membrane. The calibration curve for a standard l-Lys solution was linear from 0.1 to 3.0 mmol L⁻¹. One assay could be completed within 2 min. The sensor was applied to determine the l-Lys content in food samples such as bonito cooking water and scallop hepatopancreas. The values obtained using the sensor and conventional high-performance liquid chromatography methods were well correlated.     

Mechanistic investigations on the oxidation of <Emphasis Type="SmallCaps">l</Emphasis>-valine by diperiodatocuprate(III) in aqueous alkaline medium: a kinetic model

The oxidation of l-valine (l-val) by diperiodatocuprate(III) (DPC) in aqueous alkaline medium at a constant ionic strength of 3.0 × 10⁻³ mol dm⁻³ was studied spectrophotometrically at 298 K and follows the rate law;

Kinetics and mechanism of <Emphasis Type="Italic">L</Emphasis>-isoleucine oxidation by alkaline diperiodatoargentate(III)

The oxidation of L-isoleucine by alkaline diperiodatoargentate(III) (DPA) at 298 K and a constant ionic strength of 0.80 mol dm⁻³ was studied spectrophotometrically. The stoichiometry is [L-isoleucine]: [DPA] = 1:2. The reaction is first order in [DPA] and has less than unit order in both [L-isoleucine] and [alkali] and retarding effect in The oxidation reaction in alkaline medium has been shown to proceed via a L-isoleucine–DPA complex, which further reacts with one molecule of DPA in a rate determining step followed by other fast steps to give the products. Spot test and IR were used to identify the main products. The reaction constants involved in the different steps of the mechanism are calculated. The activation parameters with respect to the slow step of the mechanism are computed and discussed, and thermodynamic quantities are also determined. The probable active species of oxidant have been identified. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Temperature- and pressure-responsive properties of <Emphasis Type="SmallCaps">l</Emphasis>- and<Emphasis Type="SmallCaps"> dl</Emphasis>-forms of poly(<Emphasis Type="Italic">N</Emphasis>-(1-hydroxymethyl)propylmethacrylamide) in aqueous solutions

The structural transition of the l- and dl forms of poly(N-(1- hydroxymethyl)propylmethacrylamide (PHMPMA) in aqueous solution was studied by measuring the pressure dependence of the apparent scattering intensity, differential scanning calorimetry (DSC), and circular dichroism (CD). The thermodynamic implications of the results are discussed in relation to the chiral structure of the side chain, and differences in the thermal and barometric transitions. T-P diagrams of the transition showed characteristic ellipsoid features. Antagonism of the temperature and pressure effects was observed only for P(dl-HMPMA). For P(l-HMPMA), the transition temperature (T _tr) decreased with increasing pressure, and the highest T _tr was observed at atmospheric pressure (0.1 MPa). For both polymers, the highest P _trs were observed at the lowest temperatures. The l polymer showed a specific negative peak in its CD spectrum at around 220 nm in the lower temperature region and the temperature dependence was reproduced by a single-step transition, with the midpoint corresponding to the T _tr obtained from the scattering measurements. Coupled with the results from the DSC, the different behavior between the P(l-HMPMA) and P(dl-HMPMA) could be explained in terms of the chain states before and after the transition. The cooperative factors derived from the DSC measurement revealed that about 4 to 5 polymers of the present size were necessary to perform a thermal transition for P(l-HMPMA), and that P(dl-HMPMA) underwent its transition as an almost single molecular event.This revised version was published online in June 2005 with correction to the article category.     

Thermal properties of amphiphilic biodegradable triblock copolymer of <Emphasis Type="SmallCaps">l</Emphasis>,<Emphasis Type="SmallCaps">l</Emphasis>-lactide and ethylene glycol

Samples of poly(l,l-lactide)-block-poly(ethylene glycol)-block-poly(l,l-lactide) (PLLA-PEG-PLLA) were synthesized from l,l-lactide polymerization using stannous 2-ethylhexanoate, Sn(Oct)₂ as initiator and di-hydroxy-terminated poly(ethylene glycol) (PEG) (M _n  = 4000 g mol⁻¹) as co-initiator. The chemical linkage between the PEG segment and the PLA segments was characterized by Fourier transform infrared spectroscopy (FTIR). Thermogravimetry analysis (TG) revealed the copolymers composition and was capable to show the deleterious effect of an excess of Sn(Oct)₂ in the polymer thermal stability, while Differential Scanning Calorimetry (DSC) allowed the observation of the miscibility between the PLLA and PEG segments in the different copolymers.     

Enthalpy characteristics of dissolution of <Emphasis Type="SmallCaps">l</Emphasis>-cysteine and <Emphasis Type="SmallCaps">l</Emphasis>-asparagine in aqueous solutions of acetonitrile and dimethyl sulfoxide at 298.15 K

The integral enthalpies of dissolution Δ_sol H ^m of l-cysteine and l-asparagine in mixtures of water with acetonitrile and dimethyl sulfoxide at the concentration of organic solvent up to 0.32 molar fractions were measured by means of dissolution calorimetry. The standard enthalpies of dissolution (Δ_sol H°) and transfer (Δ_trans H°) of the amino acids from water to a mixed solvent were calculated. The enthalpy coefficients of pair interactions for L-cysteine and L-asparagine with cosolvent molecules are positive, except for the L-asparagine-water-acetonitrile system. The concepts on the prevailing effect of specific interactions in solutions and the influence of the nature of the cosolvents and lateral substituents of the amino acids on the thermochemical characteristics of dissolution were used to explain the data obtained.     

A kinetic analysis of oxidation of the antioxidant <Emphasis Type="Italic">N</Emphasis>-acetyl-<Emphasis Type="SmallCaps">l</Emphasis>-cysteine (NAC) by Pt(IV) complexes

N-acetyl-l-cysteine (NAC) is an antioxidant and a supplement and has been demonstrated to have protective effects for a variety of toxic effects of heavy metals. Although previous works have shown that NAC can ameliorate the severe toxic effects of cisplatin, there is a lack of understanding of the interactions between NAC and Pt(IV)-based prodrugs. In this work, the oxidation of NAC by a cisplatin prodrug (cis-[Pt(NH₃)₂Cl₄]), by a prototype of Pt(IV) anticancer drug ormaplatin ([Pt(dach)Cl₄]) and by a model compound (trans-[PtCl₂(CN)₄]^2–) was characterized in detail. NAC was oxidized to NAC-disulfide as identified by mass spectrometric analysis. Time-resolved spectral and stopped-flow kinetic measurements were carried out over a wide pH range, demonstrating that the oxidation followed overall second-order kinetics. The observed second-order rate constants k′ versus pH profiles were established. A reaction mechanism was deduced, involving three parallel rate-determining steps; conceivable transition states were also proposed for these steps. Rate constants of the rate-determining steps, obtained from the simulations of rate equation to the k′–pH profiles, were largely correlated with the electron density on the sulfur atom in NAC. The Pt(IV) prodrugs can execute oxidative stress in the biological systems of the human body by direct oxidation of relevant molecules, similar to HOCl/OCl^? and chloroamines. Instead, the oxidative stress involved in the severe toxic effects of cisplatin is produced via a different mode. NAC could be a chemoprotecting agent also for the Pt(IV) anticancer drugs if recent drug delivery technologies are used.     

Extracellular Production and Characterization of Two <Emphasis Type="Italic">Streptomyces</Emphasis><Emphasis Type="SmallCaps">l</Emphasis>-Asparaginases

l-Asparaginase (ASNase) has proved its use in medical and food industries. Sequence-based screening showed the thermophilic Streptomyces strain Streptomyces thermoluteus subsp. fuscus NBRC 14270 (14270 ASNase) to positive against predicted ASNase primary sequences. The 14270 ASNase gene and four l-asparaginase genes from Streptomyces coelicolor, Streptomyces avermitilis, and Streptomyces griseus (SGR ASNase) were expressed in Streptomyces lividans using a hyperexpression vector: pTONA5a. Among those genes, only 14270 ASNase and SGR ASNase were successful for overexpression and detected in culture supernatants without an artificial signal peptide. Comparison of the two Streptomyces enzymes described above demonstrated that 14270 ASNase was superior to SGR ASNase in terms of optimum temperature, thermal stability, and pH stability.     

Kinetics and mechanism of interaction of hexaaquachromium(III) with <Emphasis Type="SmallCaps">l</Emphasis>-Dopa in aqueous medium: comparative antiparkinsonian studies

The kinetics and mechanism of the substitution reaction between [Cr(H₂O)₆]³⁺ and l-Dopa in aqueous medium has been studied over the range 1.8 ≤ pH ≤ 2.6, 1.68 × 10⁻² mol dm⁻³ ≤ [Dopa] ≤ 5.04 × 10⁻² mol dm⁻³, I = 0.1 mol dm⁻³ (KNO₃) at 50 °C. The reaction takes place via an outer sphere association between Cr³⁺ and l-Dopa followed by chelation. The product was characterized by physicochemical and infrared spectroscopic methods. The antiparkinsonian activity of the product was found to be higher than that of l-Dopa.     

Electrochemical study of gallium(III) with <Emphasis Type="SmallCaps">l</Emphasis>-glutamine at the dropping mercury electrode

Abstract  

Gallium complexes of l-glutamine have been studied polarographically in aqueous media. The reduction was found to be irreversible and diffusion controlled in the presence of 0.1 M KNO₃ and 0.002% Triton-x-100. The values of kinetic parameters, transfer coefficient (α _n), and formal rate constant ( k_{\textf,\texth}⁰ k_{{{\text{f}},{\text{h}}}}^{0} ) of the electrode reactions were calculated by Koutecky's method. The stability constants and composition of the gallium(III)-l-glutamine complexes were evaluated with the help of the Deford-Hume method. The values of stability constants of 1:1, 1:2, and 1:3 gallium(III)-l-glutamine complexes are 1.35, 6.5, and 1,350 at 30 °C, respectively. The values of thermodynamic parameters, the free energy of activation, the enthalpy of activation, and the entropy of activation have been determined at 30 °C. The formation of the metal complexes has been found to be non-spontaneous, endothermic in nature, and entropically favorable at higher temperature.     

Poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactide) networks with tailored water sorption

A poly(l-lactide) diol was obtained through ring opening polymerization of l-lactide, using 1,6 hexanediol and tin(II) 2 ethylhexanoate as a catalyst. In the second step, the poly(l-lactide) macromer (mLA) was obtained by the reaction of poly(l-lactide) diol with methacrylic anhydride. The effective incorporation of the polymerizable end groups was assessed by Fourier transform infrared spectroscopy and nuclear magnetic resonance (¹H NMR). Besides, poly(l-lactide) networks (pmLA) were prepared by photopolymerization of mLA. Further, the macromer was copolymerized with 2-hydroxyethyl acrylate seeking to tailor the hydrophilicity of the system. A set of hydrophilic copolymer networks were obtained. The phase microstructure of the new system and the network architecture was investigated by differential scanning calorimetry, infrared spectroscopy, dynamic mechanical spectroscopy, thermogravimetry, and water sorption studies.     

Kinetics and mechanism of the reaction of hydroxopentaaquarhodium(III) ion with <Emphasis Type="SmallCaps">l</Emphasis>-Arginine in aqueous solution

The kinetics of the aqua ligand substitution from hydroxopentaaquarhodium(III) ion, [Rh(H₂O)₅(OH)]²⁺, by l-Arginine has been studied spectrophotometrically as a function of Arginine concentration, and temperature, at pH 4.3. The reaction proceeds via a rapid outer sphere association complex formation step followed by two consecutive steps. The first of these involves ligand-assisted anation, while the second involves chelation as the second aqua ligand is displaced. The association equilibrium constant for the outer sphere complex formation has been evaluated together with the rate constants for the two subsequent steps. The activation parameters for both steps have been evaluated using Eyring’s equation. Thermodynamic parameters calculated from the temperature dependence of the outer sphere association equilibrium constants are also consistent with an associative mode of activation. The product of the reaction has been characterized by conductivity measurement and IR spectroscopic analysis.     

Tyrosine alkyl esters as prodrug: the structure and intermolecular interactions of <Emphasis Type="SmallCaps">l</Emphasis>-tyrosine methyl ester compared to <Emphasis Type="SmallCaps">l</Emphasis>-tyrosine and its ethyl and <Emphasis Type="Italic">n</Emphasis>-butyl esters

l-Tyrosine alkyl esters are used as prodrugs for l-tyrosine. Although prodrugs are often designed for their behavior in solution, understanding their solid-state properties is the first step in mastering drug delivery. The crystal structure of l-tyrosine methyl ester has been determined and compared to published structures of l-tyrosine and its ethyl and n-butyl esters. It is almost isostructural with the other esters: it crystallizes in the orthorhombic chiral space group P2₁2₁2₁, a = 5.7634(15) Å, b = 12.111(2) Å, c = 14.3713(19) Å, V = 1003.1(4) Å³ with Z′ = 1. Their main packing motif is a C(9) infinite hydrogen-bond chain, but the conformation of l-tyrosine methyl ester is different from the other two: eclipsed versus U-shaped, respectively. The published structure of the ethyl ester, which was incomplete, has been confirmed by X-ray powder diffraction data. Because l-tyrosine methyl ester is very stable (28 years stored at room temperature), and its hydrolysis rate is relatively low, it should be one of the better prodrugs among the alkyl esters of tyrosine.     

Mechanistic study of the oxidation of <Emphasis Type=SmallCaps>l</Emphasis>-phenylalanine by hexacyanoferrate(III) catalyzed by iridium(III) in aqueous alkaline medium

The oxidation of l-phenylalanine by hexacyanoferrate(III) (abbreviated as HCF) catalyzed by Ir(III) has been studied spectrophotometrically at 35 °C and at a constant ionic strength of 0.50 mol dm⁻³. The main oxidation product was identified as phenylpyruvic acid by physico-chemical and spectroscopic methods. The stoichiometry was found to be 2:1, i.e. 2 mol of hexacyanoferrate(III) reacted with 1 mol of phenylalanine. The reaction was first order with respect to both HCF and alkali concentration. The order with respect to [Phe] changed from first to zero as the concentration was increased. The effect of ionic strength was also investigated. Thermodynamic parameters were evaluated by studying the reaction at four different temperatures between 35 and 50 °C. Based on the experimental results, a suitable mechanism involving complex formation has been proposed.     

Development of an Amperometric Biosensor Platform for the Combined Determination of <Emphasis Type="SmallCaps">l</Emphasis>-Malic,Fumaric, and <Emphasis Type="SmallCaps">l</Emphasis>-Aspartic Acid

Three amperometric biosensors have been developed for the detection of l-malic acid, fumaric acid, and l -aspartic acid, all based on the combination of a malate-specific dehydrogenase (MDH, EC 1.1.1.37) and diaphorase (DIA, EC 1.8.1.4). The stepwise expansion of the malate platform with the enzymes fumarate hydratase (FH, EC 4.2.1.2) and aspartate ammonia-lyase (ASPA, EC 4.3.1.1) resulted in multi-enzyme reaction cascades and, thus, augmentation of the substrate spectrum of the sensors. Electrochemical measurements were carried out in presence of the cofactor β-nicotinamide adenine dinucleotide (NAD⁺) and the redox mediator hexacyanoferrate (III) (HCFIII). The amperometric detection is mediated by oxidation of hexacyanoferrate (II) (HCFII) at an applied potential of + 0.3 V vs. Ag/AgCl. For each biosensor, optimum working conditions were defined by adjustment of cofactor concentrations, buffer pH, and immobilization procedure. Under these improved conditions, amperometric responses were linear up to 3.0 mM for l-malate and fumarate, respectively, with a corresponding sensitivity of 0.7 μA mM^?1 (l-malate biosensor) and 0.4 μA mM^?1 (fumarate biosensor). The l-aspartate detection system displayed a linear range of 1.0–10.0 mM with a sensitivity of 0.09 μA mM^?1. The sensor characteristics suggest that the developed platform provides a promising method for the detection and differentiation of the three substrates.     

Studies on synthesis and in vitro biodegradability of novel optically active nanostructure poly(ester-imide)s containing <Emphasis Type="SmallCaps">l</Emphasis>-phenylalanine and <Emphasis Type="SmallCaps">l</Emphasis>-isoleucine linkages

A series of biodegradable functional amino-acid-based poly(ester-imide)s (PEI)s were designed and synthesized by the direct polycondensation reaction of chiral diacids composed of naturally occurring α-amino acids with 4,4′-thiobis(2-tert-butyl-5-methylphenol) in the presence of tosyl chloride, pyridine, and N,N-dimethylformamide as a condensing agent. These new chiral polymers were characterized with respect to chemical structure and purity using specific rotation experiments, FT-IR, ¹H-NMR, techniques, and elemental analysis. The surface morphology of these polymers was investigated by field emission scanning electron microscopy. The result indicated nanoscale morphology of the obtained polymers. Thermal stability and the weight loss behavior of the resulting PEIs were studied by TGA techniques. All PEIs showed no significant weight loss below 400 °C in a N₂ environment. The monomers and prepared polymers were co-cultivated with airborne fungal spores in culture media to study their biological activity. Soil burial test was also used for evaluation of their biodegradation behavior. The results showed that the synthesized monomers and their derived polymers are biologically active and that their degradation products are probably nontoxic to microbial growth.     

Ferrocene-containing tri- and tetranuclear cyclic copper(<Emphasis Type="SmallCaps">i</Emphasis>) and silver(<Emphasis Type="SmallCaps">i</Emphasis>) pyrazolates

New tri- and tetranuclear macrocyclic silver(i) and copper(i) 3-ferrocenyl-5-(trifluoromethyl)pyrazolates were prepared: [{(3-((η⁵-C₅H₄)Fe(η⁵-C₅H₅))-5-(CF₃)-Pz}M]₃ (M = Cu (1), Ag (2)) and [{(3-(( η⁵-C₅H₄)Fe(η⁵-C₅H₅))-5-(CF₃)-Pz}Cu]₄ (3). The structures of compounds were established by X-ray diffraction analysis. In the crystalline state, a planar trinuclear silver-containing macrocycliс pyrazolate and a saddle-shaped tetranuclear copper-containing macrocycle are formed. The introduction of a bulky substituent, ferrocene, into the pyrazole ligand results in complete shielding of the acidic metal sites, which precludes the coordination of base molecules.