Synthesis, characterization and biodegradable studies of 1,3-propanediol based polyesters

A series of biodegradable polyesters were synthesized from dicarboxylic acids and 1,3-propanediol catalyzed by transestrification polycondensation reaction in the bulk. The structure, average molecular weights and physical properties of the resulting aliphatic polyesters were characterized by ¹H NMR, FT-IR, solution viscosity, GPC, DSC and TGA. Homopolyesters show higher degree of crystallinity, melting and thermal stability in comparison to copolyesters. The biodegradability of the polyesters was determined by monitoring the normalized weight loss of polyester films with time in phosphate buffer (pH 7.2) without and with Rhizopus delemar lipase at 37 °C. The rate of enzymatic degradation of homopolyesters follows the path PPSu > PPAd > PPSe. PPSe did not show significant weight loss in presence of enzyme which may be due to its highest degree of crystallinity and melting point compared to the PPSu, PPAd and copolyesters. In the soil burial degradation polyester sample showed severe surface degradation by the attack of microorganism.     

Capillary electrophoresis-electrochemiluminescent detection of N,N-dimethyl ethanolamine and its application in impurity profiling and stability investigation of meclophenoxate

Numerous drugs are carboxylic acid derivatives containing amino group, and hydrolysis reaction of these agents often generates toxic amines. Thus, the detection of amine impurity is of great importance in drug quality control of these amino group-containing ester and amide. A capillary electrophoresis method coupled with end-column electrochemiluminescent detection based on tris(2,2′-bipyridyl)ruthenium(II) system was proposed for the analysis of N,N-dimethyl ethanolamine (DMEA, the degradation product of meclophenoxate) in the presence of its precursor. Baseline separation of DMEA and meclophenoxate can be easily achieved under the selected conditions. DMEA can be assayed within 3 min over the concentration range of 5.0 × 10⁻⁸ to 3.0 × 10⁻⁶ mol L⁻¹ with a detection limit of 2.0 × 10⁻⁸ mol L⁻¹ at the signal-to-noise ratio of 3. The relative standard deviations of the signal intensity and the migration time were less than 5.3 and 2.5% for a standard sample containing 1.0 × 10⁻⁷ mol L⁻¹ DMEA (n = 5), respectively. The presented method has been successfully applied for the profiling of DMEA resulting from the hydrolysis of meclophenoxate in commercial formulations. A primary stability investigation of meclophenoxate in aqueous solution was also carried out at different temperatures, and the results showed that the degradation of meclophenoxate accelerated at the higher temperature.     

Synthesis, characterization and intercalation property of layered zirconium benzylamino-N,N-dimethylphosphonate phosphate materials

Layered zirconium benzylamino-N,N-dimethylphosphonate phosphate (ZBMPA) was prepared by the reaction of zirconyl chloride with benzylamino-N,N-dimethylphosphonic acid (H₂BMPA) and phosphoric acid in the presence of hydrofluoric acid. The intercalation of n-alkylamines (n-butylamine, n-heptylamine and n-decylamine) into ZBMPA was primarily investigated at room temperature. These materials were characterized by elemental analysis, ICP, XRD, SEM, FT-IR, Raman spectra, TG and DSC. The composition of ZBMPA is Zr(HPO₄)(C₆H₅CH₂N(CH₂PO₃)₂)_0.5 · 2.0H₂O. The interlayer distance of ZBMPA, n-butylamine, n-heptylamine and n-decylamine intercalation compounds is 2.03, 2.58, 2.52 and 3.17 nm, respectively. ZBMPA and the n-alkylamine intercalation compounds are different in the morphology and vibration spectra. Thermogravimetries of all materials obtained reveal three step mass losses at temperatures of up to 1000 °C. These results indicate that n-alkylamines are intercalated into the galleries of host ZBMPA.     

Bis-β-sulfanylethylester and cyclic disulfide-S-oxides as precursors of bifunctionalized anionic derivatives with two oxidized sulfurs

The cyclic disulfide and the bis-β-sulfanyl ethyl ester derived from dithiol, N,N′-1,2-phenylenebis(3-methyl-3-sulfanylbutanamide) were used as precursors to prepare upon oxidation the cyclic disulfide-S-oxides and the thioether sulfur oxidized species including thioether/sulfoxide, bis-sulfoxide, sulfoxide/sulfone, and bis-sulfone. Ring cleavage with KOH/EtOH of the cyclic disulfide-S-monooxide followed by reaction of the opened intermediate with ethyl acrylate afforded the sulfinate/β-sulfanyl ethyl ester derivative. Selective oxidation with 1 and 2 equiv of (3S)-3-tert-butyl-3-methyl-2-(phenylsulfonyl)oxaziridine or with 3 equiv of DMD led to the isolation of a series of compounds containing a sulfonate and a β-sulfanyl, a β-sulfinyl, and a β-sulfonyl ethyl ester. Retro-Michaël reaction applied to the β-sulfonyl/β-sulfinyl and bis-β-sulfonyl derivatives enabled to produce compounds containing a sulfinate and a β-sulfinyl or a β-sulfonyl ethyl ester as well as the bis-sulfinate dianion. DMD oxidation of the latter afforded the bis-sulfonate dianion. All these anionic species were characterized by ¹H NMR, mass spectrometry, HRMS or elemental analysis. Sulfenates in such pseudopeptidic structures could not be isolated from the ring cleavage of the cyclic disulfide-S-dioxide or from a retro-Michaël reaction applied to the β-sulfinyl ethyl ester. A cyclization reaction leading to an isothiazolidin-3-one is likely to occur as observed from the ring cleavage of the cyclic disulfide-S-dioxide. Finally, Ni(II) and Co(III) have been inserted into the disulfinate dianion leading to the corresponding diamidato/disulfinato complexes S-bonded to Ni(II) or Co(III) centers.     

Synthesis, characterization and Schlenk equilibrium studies of methylmagnesium compounds with O- and N-donor ligands - the unexpected behavior of [MgMeBr(pmdta)] (pmdta = N,N,N′,N″,N″-pentamethyldiethylenetriamine)

MgMe₂ (1) was found to react with 1,4-diazabicyclo[2.2.2]octane (dabco) in tetrahydrofuran (thf) yielding a binuclear complex [{MgMe₂(thf)}₂(μ-dabco)] (2). Furthermore, from reactions of MgMeBr with diglyme (diethylene glycol dimethyl ether), NEt₃, and tmeda (N,N,N′,N′-tetramethylethylenediamine) in etheral solvents compounds MgMeBr(L), (L = diglyme (5); NEt₃ (6); tmeda (7)) were obtained as highly air- and moisture-sensitive white powders. From a thf solution of 7 crystals of [MgMeBr(thf)(tmeda)] (8) were obtained. Reactions of MgMeBr with pmdta (N,N,N′,N″,N″-pentamethyldiethylenetriamine) in thf resulted in formation of [MgMeBr(pmdta)] (9) in nearly quantitative yield. On the other hand, the same reaction in diethyl ether gave MgMeBr(pmdta) · MgBr₂(pmdta) (10) and [{MgMe₂(pmdta)}₇{MgMeBr(pmdta)}] (11) in 24% and 2% yield, respectively, as well as [MgMe₂(pmdta)] (12) as colorless needle-like crystals in about 26% yield. The synthesized methylmagnesium compounds were characterized by microanalysis and ¹H and ¹³C NMR spectroscopy. The coordination-induced shifts of the ¹H and ¹³C nuclei of the ligands are small; the largest ones were found in the tmeda and pmdta complexes. Single-crystal X-ray diffraction analyses revealed in 2 a tetrahedral environment of the Mg atoms with a bridging dabco ligand and in 8 a trigonal-bipyramidal coordination of the Mg atom. The single-crystal X-ray diffraction analyses of [MgMe₂(pmdta)] (12) and [MgBr₂(pmdta)] (13) showed them to be monomeric with five-coordinate Mg atoms. The square-pyramidal coordination polyhedra are built up of three N and two C atoms in 12 and three N and two Br atoms in 13. The apical positions are occupied by methyl and bromo ligands, respectively. Temperature-dependent ¹H NMR spectroscopic measurements (from 27 to −80 °C) of methylmagnesium bromide complexes MgMeBr(L) (L = thf (4); diglyme (5); NEt₃ (6); tmeda (7)) in thf-d₈ solutions indicated that the deeper the temperature the more the Schlenk equilibria are shifted to the dimethylmagnesium/dibromomagnesium species. Furthermore, at −80 °C the dimethylmagnesium compounds are predominant in the solutions of Grignard compounds 4-6 whereas in the case of the tmeda complex7 the equilibrium constant was roughly estimated to be 0.25. In contrast, [MgMeBr(pmdta)] (9) in thf-d₈ revealed no dismutation into [MgMe₂(pmdta)] (12) and [MgBr₂(pmdta)] (13) even up to −100 °C. In accordance with this unexpected behavior, 1:1 mixtures of 12 and 13 were found to react in thf at room temperature yielding quantitatively the corresponding Grignard compound 9. Moreover, the structures of [MgMeBr(pmdta)] (9c), [MgMe₂(pmdta)] (12c), and [MgBr₂(pmdta)] (13c) were calculated on the DFT level of theory. The calculated structures 12c and 13c are in a good agreement with the experimentally observed structures 12 and 13. The equilibrium constant of the Schlenk equilibrium (2 9c ? 12c + 13c) was calculated to be K_gas = 2.0 × 10⁻³ (298 K) in the gas phase. Considering the solvent effects of both thf and diethyl ether using a polarized continuum model (PCM) the corresponding equilibrium constants were calculated to be K_thf = 1.2 × 10⁻³ and K_ether = 3.2 × 10⁻³ (298 K), respectively.     

Glycolysis of poly(ethylene terephthalate) (PET) using basic ionic liquids as catalysts

The glycolysis of poly(ethylene terephthalate) (PET) was studied using several ionic liquids and basic ionic liquids as catalysts. The basic ionic liquid, 1-butyl-3-methylimidazolium hydroxyl ([Bmim]OH), exhibits higher catalytic activity for the glycolysis of PET, compared with 1-butyl-3-methylimidazolium bicarbonate ([Bmim]HCO₃), 1-butyl-3-methylimidazolium chloride ([Bmim]Cl) and 1-butyl-3-methylimidazolium bromide ([Bmim]Br). FT-IR, ¹H NMR and DSC were used to confirm the main product of glycolysis was bis(2-hydroxyethyl) terephthalate (BHET) monomer. The influences of experimental parameters, such as the amount of catalyst, glycolysis time, reaction temperature, and dosages of ethylene glycol on the conversion of PET, yield of BHET were investigated. The results showed a strong influence of the mixture evolution of temperature and reaction time on depolymerization of PET. Under the optimum conditions of m(PET):m(EG): 1:10, dosage of [Bmim]OH at 0.1 g (5 wt%), reaction temperature 190 °C and time 2 h, the conversion of PET and the yield of BHET were 100% and 71.2% respectively. Balance between the polymerization of BHET and depolymerization of PET could be changed when the reaction time was more than 2 h and contents of catalyst and EG were changed.     

Vapor–liquid equilibria for water + acetic acid + (N,N-dimethylformamide or dimethyl sulfoxide) at 13.33 kPa

Isobaric vapor–liquid equilibrium (VLE) data of the systems acetic acid + N,N-dimethylformamide (DMF), acetic acid + dimethyl sulfoxide (DMSO), DMSO + water, water + acetic acid + DMF, and water + acetic acid + DMSO have been measured at 13.33 kPa by using an improved Rose equilibrium still. The association of acetic acid in vapor phase has been considered, and the nonideality of vapor phase was accounted for using the Hayden–O’Connell (HOC) method. The experimental binary data have been correlated by the NRTL, Wilson and van Laar models. The NRTL model parameters obtained from the binary data have been used to predict the ternary VLE data. The ternary predicted values obtained in this way agree well with the experimental values.     

New N,N-amino-diphosphonate-containing methacrylic derivatives, their syntheses and radical copolymerizations with MMA

Hydroxy-amino-diphosphonates HO-C_n-NH₂, with 2 ? n ? 11, have been successfully synthesized via the Kabachnick-Field reaction at 70 °C with high yields. These hydroxy compounds are then reacted with methacryloyl chloride to lead to novel amino-diphosphonate methacrylates MAC_nNP₂ (with 2 ? n ? 11). These highly pure methacrylate monomers were obtained with yields higher than 75%. Radical copolymerizations of MAC_nNP₂ (with 2 ? n ? 11) with MMA have been conducted and the r₁ values (related to MAC_nNP₂) are in the range of 1.1-1.3, and r₂ values (related to MMA) about 0.8; this shows that the diphosphonate groups are statistically bonded to the methacrylic backbone.     

Aqueous sols of oligo(ethylene glycol) surface decorated polydiacetylene vesicles for colorimetric detection of Pb 2+

A series of ethylene glycol (EG), triethylene glycol (3EG) and pentaethylene glycol (5EG) esters of 10,12-pentacosadiynoic acid (PCDA) are synthesized. The glycol ester lipids can be hydrated and well dispersed in water but they cannot form polydiacetylenes upon UV irradiation. They however can be mixed with PCDA up to 30 mol% and polymerized to form blue sols. The mixed polydiacetylene sols show blue to red thermochromic transition with two-stepped transition temperatures. The first transition temperature decreases with the increase of the glycol ester content as well as the length of their chains indicating greater fluidity of the self-assembled structure due to less collaborative hydrogen bonding among the lipid head groups. These mixed polydiacetylene sol prepared from 30 mol% of the penta(ethylene glycol) ester show linear colorimetric response selectively to Pb²⁺ in the range of 5-30 μM.     

Micellar electrokinetic chromatography-chemiluminescent detection of biogenic amines using N-(4-aminobutyl)-N-ethylisoluminol as derivatization reagent and trivalent copper chelate as chemiluminescence enhancer

A facile, sensitive and universal method was established for analysis of biogenic amines using micellar electrokinetic chromatography coupled with chemiluminescent (CL) detection. It was found that diperiodatocuprate (III) (K₅[Cu(HIO₆)₂], DPC), a transition metal chelate at unstable high oxidation state, could effectively enhance the reaction between luminol-type compound and hydrogen peroxide, to produce very strong CL signal. In addition, triethylamine was found to be able to effectively improve the yield of the derivatization reaction between biogenic amines and a luminol-type derivatization reagent, N-(4-aminobutyl)-N-ethylisoluminol (ABEI). Based on these facts, three biogenic amines were pre-column derivatized with ABEI, and post-column detected using high sensitive luminol-hydrogen peroxide-DPC CL system. Since the background was quite low, and the signal was quite strong, a considerable improved sensitivity was obtained. The presented method had been successfully applied to simultaneously analyze glycine, proline and phenylalanine with the detection limits (S/N = 3) of 0.030 μmol L⁻¹, 0.23 μmol L⁻¹ and 0.21 μmol L⁻¹, respectively. To evaluate its potential application value, glycine in saliva and urine samples was detected using this method, and satisfied results were obtained. This approach can be further extended to detection of many other compounds such as peptides and drugs by using luminol-type derivatization reagent.     

Synthesis, characterization and in vitro degradation study of a novel and rapidly degradable elastomer

Biodegradable elastomers represent a useful class of biomaterials. In this paper, a novel biodegradable elastomer, poly(PEG-co-CA) (PEC), was synthesized by condensation of poly(ethylene glycol) (PEG) and citric acid (CA) under atmospheric pressure without any catalyst. We first synthesized a pre-polymer by carrying out a controlled condensation reaction between PEG and citric acid, and then post-polymerised and simultaneously cross-linked the pre-polymer in the mould at 120 °C. The pre-polymer was characterized by FT-IR, ¹H NMR, ¹³C NMR, GPC and DSC. A series of polymers were prepared at different post-polymerisation time and different monomer ratios. Measurements on the mechanical properties of PEC testified that the new polymers are elastomers with low hardness and big elongation, and hydrolytic degradation of the polymer films in a buffer of pH 7.4 at 37 °C showed that PEC had excellent degradability (all the films show the weight losses more than 60% after 96 h incubation). The different post-polymerisation time and monomer ratio had strong influence on the degradation rates and mechanical performances. The material is expected to be useful for controlled drug delivery and other biomedical applications.     

Aging and thermal degradation of poly(N-methylaniline)

The conductivity aging and thermal stability of poly(N-methylaniline) are reported. Poly(N-methylaniline) doped with chloride ion was electrochemically synthesized. The conductivity data obtained in the temperature range between 118 and 483 K are analysed by Arrhenius and Mott models to elucidate the conduction mechanism. The thermal degradation of both doped and dedoped samples of poly(N-methylaniline) in air and nitrogen atmosphere has been followed using thermogravimetric and differential thermal analysis techniques. The polymer is heat-aged at various temperatures and the aged samples are analysed by FT-IR, SEM and XRD. The thermogravimetric data are further analysed by three different methods: Horowitz and Metzger [Anal. Chem. 35 (1963) 1464], Coats and Redfern [Nature 201 (1964) 68], Chan et al. [Synth. Met. 31 (1989) 95] to evaluate the energy of activation. The applicability of the three methods for the evaluation of kinetic parameters is discussed.     

Cyclizations of 2-alkylthiazolines and 2-alkyloxazolines with α,α-disubstituted diacid chlorides or N-(chlorocarbonyl) isocyanate

Two-step cyclizations of 2-alkylthiazolines or 2-alkyloxazolines with α,α-disubstituted diacid chlorides produce excellent yields of 6,6-dialkyl-2,3-dihydrothiazolo[3,2-a]pyridine-5,7-diones and 6,6-dialkyl-2,3-dihydrooxazolo[3,2-a]pyridine-5,7-diones in refluxing acetonitrile containing Et₃N. Similar cyclizations using N-(chlorocarbonyl) isocyanate in place of diacid chlorides produced 2,3-dihydrothiazolo[3,2-c]pyrimidine-5,7-diones or 2,3-dihydrooxazolo[3,2-c]pyrimidine-5,7-diones, respectively. Each cyclization proceeded through cyclic ketene-N,X-acetal (X = O or S) intermediates.     

FT-IR measurement of tagitinin C after solvent extraction from Tithonia diversifolia

Tagitinin C, an antiplasmodial compound, identified as one major compound of the subtropical medicinal plant, Tithonia diversifolia, was determined by FT-IR spectroscopy method. The crude ether extracts from aerial parts of the plant were evaporated to dryness and re-dissolved in tetrachloroethylene (C₂Cl₄) before analysis.The magnitude of the absorbance of the very specific CO stretching vibration (ν_CO) at 1664.8 cm⁻¹ was exploited in order to quantify tagitinin C. The determination coefficient (r²) of the calibration scale was 0.9994, the detection limit was lower than 3 μg ml⁻¹ and the quantification limit was lower than 10 μg ml⁻¹.Recovery values from 100.5 to 101.7% were found for spiked concentration levels from 19.91 to 89.95 μg ml⁻¹. The main characteristics of the curves obtained from the calibration standards and from the standard addition technique were not statistically different (Student t-test) suggesting that matrix effects were negligible.The results obtained for the determination of tagitinin C in the crude ether extract from aerial parts of T. diversifolia by LC and FT-IR spectroscopic method agreed well: 0.76±0.02 and 0.773±0.009, of tagitinin C in dried plant respectively.     

Matrix isolation FT-IR spectroscopy and molecular orbital study of sarcosine methyl ester

N-methylglycine methyl ester (sarcosine-Me) has been studied by matrix isolation FT-IR spectroscopy and molecular orbital calculations undertaken at the DFT/B3LYP and MP2 levels of theory with the 6-311++G(d,p) and 6-31++G(d,p) basis set, respectively. Twelve different conformers were located in the potential energy surface of the studied compound, with the ASC conformer being the ground conformational state. This form is analogous to the dimethylglycine methyl ester most stable conformer and is characterized by a NH?O intramolecular hydrogen bond; in this form, the ester group assumes the cis configuration and the OC-C-N and Lp-N-C-C (where Lp is the nitrogen lone electron pair) dihedral angles are ca. −17.8 and 171.3°, respectively. The second most stable conformer (GSC) differs from the ASC conformer essentially in the conformation assumed by the methylamino group, which in this case is gauche (Lp-N-C-C dihedral angle equal to 79.4°). On the other hand, the third most stable conformer (AAC) differs from the most stable form in the conformation of the OC-C-N axis (151.4°). These three forms were predicted to differ in energy by less than ca. 5 kJ mol⁻¹ and represent ≈95% of the total conformational population at room temperature. FT-IR spectra were obtained for sarcosine-Me isolated in argon matrices revealing the presence in the matrices of the three lowest energy conformers predicted by the calculations. The matrices were prepared by deposition of the vapour of the compound using two different nozzle temperatures, 25 and 60 °C. The relative populations of the three conformers trapped in the matrices were found to be consistent with occurrence of conformational cooling during matrix deposition and with a stabilization of the most polar GSC and AAC conformers in the matrices compared to the gas phase. Indeed, like it was previously observed for the methyl ester of dimethylglycine [Phys. Chem. Chem. Phys. 5 (2003) 52] the different strength of the interactions between the conformers and the matrix environment seem to lead to a change in the relative order of stabilities of GSC and ASC upon going from the gas phase to the matrices, with the first conformer becoming the conformational ground state in the latter media. The assignment of the bands observed in the matrix spectra to the three experimentally observed conformers of sarcosine-Me is presented and discussed.     

N,N-polymethylene-bisadenine complexes with d metal ions

The reaction of N⁹,N^9′-(tri or tetramethylene)-bisadenines (Ade₂C_x; x = 3 or 4) in HCl 2 M at 50 °C with MCl₂ · 2H₂O [M = Zn(II), Cd(II)] yields outer sphere compounds like the previously described [(H-Ade)₂C₃][ZnCl₄] · H₂O (3) and [(H-Ade)₂C₃]₂[Cd₂Cl₈(H₂O)₂] · 4H₂O (4) for Ade₂C₃ and the new {[(H-Ade)₂C₄][Cd₂Cl₆(H₂O)₂] · 2H₂O}_n (5) for Ade₂C₄. On the other hand, only in case of Zn(II) complexes by changing [HCl] to 0.1 M, the inner sphere compounds [H-(Ade)₂C₃(ZnCl₃)] (6) and [H-(Ade)₂C₄(ZnCl₃)] · 1.5H₂O (7) are obtained. X-ray diffraction study of compound 6, which represents the first inner sphere complex with a N⁹,N^9′-bisadenine, shows a zwitterionic form with one adenine ring protonated at N(1) while the other ring is coordinated via N(7) to a ZnCl₃ moiety as in other alkyl-adenine derivatives. In addition, with Ade₂C₄, is also possible to obtain another inner sphere complex: [(H-Ade)₂C₄(ZnCl₃)₂] · 3H₂O (8).     

Acyclic tertiary diamines and 1,4,7,10-tetraazacyclododecane with fluorine-containing β-diketones: Leading to low melting ionic adducts

N,N,N′,N′-Tetramethylmethanediamine (1a), N,N,N′,N′-tetramethylethanediamine (1b), N,N,N′,N′-tetramethyl-1,3-propanediamine (1c), and N,N,N′,N′-tetramethyl-1,6-hexanediamine (1d) were reacted at 25 °C with 1,1,1,5,5,5-hexafluoro-2,4-pentanedione (2a), 2,2-dimethyl-6,6,7,7,8,8,8-heptafluoro-3,5-octanedione (2b), 2-thenoyltrifluoroacetone (2c), and 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione (2d) to form the ionic adducts 3-18. 1,4,7,10-Tetraazacyclododecane (1e) reacted at 25 °C with β-diketones (2a-d) and 1,1,1-trifluoro-2,4-pentanedione (2e) to give ionic solids 19-23 in good yields. Some of the products are liquid at 25 °C and are thermally stable over long liquid ranges as determined by thermal gravimetric analyses. Single-crystal X-ray structure determinations show that compounds 9 and 21 crystallize in the monoclinic space groups P2(1)/c and P2(1)/n, respectively. All the new compounds were characterized by ¹H, ¹⁹F and ¹³C NMR, electrospray MS and/or elemental analyses.     

Development and validation of a capillary zone electrophoresis method for the determination of propranolol and N-desisopropylpropranolol in human urine

A simple, rapid and sensitive procedure using solid phase extraction and capillary zone electrophoresis for the determination of propranolol (a beta-blocker) and one of its metabolites, N-desisopropylpropranolol, has been developed and validated. The optimum separation of both analytes was obtained in a 37 cm × 75 μm fused silica capillary using 20 mmol/L phosphate buffer (pH 2.2) as electrolyte, at 25 kV and 30 °C, and hydrodynamic injection for 5 s. Prior to the electrophoretic separation, the samples were cleaned up and concentrated using a C₁₈ cartridge and then, eluted with methanol, allowing a concentration factor of 30.Good results were obtained in terms of precision, accuracy and linearity. The limits of detection were 28 and 30 μg/L for N-desisopropylpropranolol and propranolol, respectively. Additionally, a robustness test of the method was carried out using the Plackett-Burman fractional factorial model with a matrix of 15 experiments.The presented method has been applied to the determination of both compounds in human urine.     

Crystal structure,spectroscopy and magnetism of a dinuclear strongly antiferromagnetically coupled N-oxido-bridged Cu(II) compound with 2,2′-bipyridine-1,1′-dioxide (bpdo) as a ligand; [Cu2(bpdo)2Br4]

A new dinuclear compound, [Cu₂(bpdo)₂Br₄], (in which bpdo = 2,2′-Bipyridine-1,1′-dioxide), has been synthesized and fully characterized, including the X-ray and the magnetic susceptibility. Each copper(II) ion in the dinuclear compound has a distorted square pyramidal geometry with the basal plane formed by two oxygen atoms of two ligand molecules which are bridging between the Cu ions with Cu–O distances of 2.021(2) and 2.039(2) Å and two bromide atoms with Cu–Br distances of 2.3577(6) and 2.3665(7) Å. The fifth position is occupied by a non bridging oxygen atom of a ligand with a Cu–O distance of 2.197(2) Å. The distance between the Cu ions is 3.334 Å, while the Cu–O–Cu angle is 110.37(9)°. The magnetic susceptibility measurements (from 5 to 350 K) agree with a very strong antiferromagnetic interaction with a large singlet–triplet splitting (J) of −905 cm⁻¹. At high T (above 250 K) a triplet powder EPR is observed.     

Determination of kynurenine levels in rat plasma by high-performance liquid chromatography with pre-column fluorescence derivatization

Kynurenine (KYN), a tryptophan metabolite, is a crucial compound for modulating neurotransmission because it can be metabolized in vivo into both quinolinic acid and kynurenic acid, which are the agonist and antagonist, respectively, of N-methyl-d-aspartate receptor. For the highly sensitive detection of KYN by high-performance liquid chromatography (HPLC), a fluorescence derivatization of KYN with a benzofurazan-type fluorogenic reagent, 4-N,N-dimethylaminosulfonyl-7-fluoro-2,1,3-benzoxadiazole (DBD-F) was investigated in the present study. KYN was derivatized with DBD-F (DBD-KYN) at 60 °C for 30 min, and separated on an octadecylsilica column with a gradient elution of the mobile phase, which consists of 0.1% formic acid in acetonitrile/methanol/water. DBD-KYN was detected fluorimetrically at 553 nm with an excitation wavelength of 431 nm. The limits of detection and quantification were approximately 0.30 pmol [signal-to-noise ratio (S/N) 3] and 1.0 pmol (S/N, 10) on column, respectively. Plasma KYN levels were successfully determined using 10 μL of rat plasma with satisfactory precision and accuracy. Intra- and inter-day precisions and accuracies were 1.7-6.8%, and −10 to 9.6%, respectively. KYN levels in plasma of male Sprague-Dawley rats (7 weeks old) were approximately 2.4 ± 0.32 μmol L⁻¹ (n = 4). The proposed HPLC method was applied to determine KYN levels in the plasma of ketamine-treated rats—the animal model of schizophrenia.