Polyfunctional isocytosine derivatives: II. Regioselectivity of methylation of 2-(2-hydroxyethylamino)-6-methylpyrimidin-4(3H)-one in different media

High regioselectivity in the methylation of 2-(2-hydroxyethylamino)-6-methylpyrimidin-4-(3H)-one at the N³ atom in water and ethanol in the presence of inorganic bases is determined by participation of the oxygen atom in hydrogen bonding and its coordination to metal cation, respectively. In going to aprotic dimethylformamide which is capable of solvating cations, the regioselectivity decreases, and a mixture of N ³-and O-methyl isomers is formed.     

Synthesis of a novel chelating ligand from pentane-2,4-dione and 3-aminopropyl[tris(trimethylsilyloxy)]silane. europium(III) and erbium(III) imino enolates

Acetylacetone reacts with 3-aminopropyl[tris(trimethylsilyloxy)]silane to give a mixture of the isomers 4-[3′-tris(trimethylsilyloxy)silylpropyl]iminopent-2-en-2-ol (90%) and 4-[3′-tris(trimethylsilyloxy)silylpropyl]aminopent-3-en-2-one (10%). According to ¹H and ¹³C NMR data, both isomers exist in the cis-and trans-forms. Anhydrous europium(III) and erbium(III) tris{4-[3′-tris(trimethylsilyloxy)silylpropyl]iminopent-2-en-2-olates} were obtained from the mixture of the isomers and the corresponding propan-2-olates Eu(OPr _i )₃ and Er(OPr _i )₃. The resulting complexes are transparent air-stable liquids that are distillable in vacuo and well soluble in photopolymerizable polyorganosiloxane caoutchoucs and urethane acrylate oligomers. The volatility parameters of the europium(III) complex were studied.     

Simultaneous determination of l(+)- and d(−)-lactic acid by use of immobilized enzymes in a flow-injection system

The system comprises l(+)- and d(?)-lactate dehydrogenase reactors in parallel and a diaphorase electrode. Separate peaks are obtained for l(+)- and d(?)-lactic acid. The peak current is linearly related to the concentration of both isomers in the range 1 × 10^?5?2 × 10^?3 M.     

Reaction of N-substituted 2-oxochromen-3-carboxamides with bromoderivatives of zinc enolates prepared from alkyl 2,2-dialkyl-4,4-dibromo-3-oxoalkanoates and zinc

Zinc enolates obtained from ethyl 2,2-dialkyl-4,4-dibromo-3-oxobutanoates and zinc react with N-substituted 2-oxochromen-3-carboxamides forming ethyl 3-{1a-(R³-carbamoyl)-2-oxo-1a,7b-dihydrocyclopropa[c]chromen-1-yl}-2,2-dialkyl-3-oxopropanoate isomer with a Z-position of methine hydrogens. Zinc enolates prepared from alkyl 2,2-dialkyl-4,4-dibromo-3-oxopentanoates and-hexanoates and zinc react with N-substituted 2-oxochromen-3-carboxamides to give rise to esters of 3-{1-alkyl-1a-(R³-carbamoyl)-2-oxo-1a,7b-dihydrocyclopropa-[c]chromen-1-yl}-2,2-dialkyl-3-oxopropanoic acid as isomers with the E-position of the methine proton and the alkyl substituent. The reaction carried out in the presence of small quantities of THF and HMPA leads to the formation of 9c-alkyl-2-R³-9b,9c-dihydro-5-oxa-2-azacyclopenta[2,3]-cyclopropa[1,2-a]naphthalene-1,3,4-triones. Zinc enolates from alkyl 2,2-dialkyl-4,4-dibromo-3-oxopentanoates and-hexanoates and zinc with the secondary amides of 2-oxochromen-3-carboxylic acid form alkyl 3-{2-oxo-1a-(piperidinocarbonyl)-and 3-{6-R¹-1a-(morpholinocarbonyl)-2-oxo-1a,7b-dihydrocyclopropa[c]chromen-1-yl}-2,2-R²,R²-3-oxopropanoates as single geometrical isomers.     

Voltammetric and spectroscopic analysis of interactions of pyridine mono-carboxylic acid isomers with cysteine at physiological pH

The interactions of pyridine mono-carboxylic acid isomers (PCAIs) (nicotinic acid (NA), isonicotinic acid (INA) and picolinic acid (PA)) with cysteine (RSH) at physiological pH (7.40) have been investigated by square-wave and cyclic voltammetry (SWV and CV), and UV-Vis and infrared spectroscopy. By the addition of isomeric pyridine mono-carboxylic acids, the reduction peak current of mercurous cysteine thiolate could be decreased and also its peak potential E _p was shifted to more positive values. Also, the significant changes in formal potential E ⁰′, electron transfer coefficient α and electrode reaction standard rate constant k _s of mercurous cysteine thiolate (Hg₂(SR)₂) in the presence and absence of PCAIs were observed. The results of voltammetric measurements indicated that binding reactions were occurred between PCAIs and RSH and new electroactive molecular complexes were formed, which resulted in the decrease of free cysteine concentration and the decrease of the reduction peak current of mercurous cysteine thiolate. The logarithmic values of binding constants of NA, INA and PA were calculated as 13.4, 17.7 and 18.9, respectively. The binding ratios for NA-RSH, INA-RSH and PA-RSH complexes were determined as 1: 3, 1: 4 and 1: 4, respectively. Both UV-Vis and FTIR studies also confirmed these interaction reactions.     

496—Cyclic voltammetric studies on the application of carbon elctrodes in the determination of oxalic acid

The application of carbon paste and glassy carbon electrodes in the analysis of oxalic acid was investigated by comparing the characteristics of cyclic voltammograms of oxalic acid obtained in various supporting electrolytes (acetate, borate, citrate, phosphate, etc.). When a semi-micro carbon paste electrode (area 0.49 cm²) was used, the oxalic acid was oxidized at +1.0 to +1.2 V vs Ag|AgCl yielding current in the μA range (scan rate 50 mV/s) for oxalic acid concentration of approximately 10^?4M. Oxalic acid oxidation was observed under both acidic and alkaline conditions. The presence of chloride ions or oxygen did not have any deleterious effect on the electrode response. The peak current was reproducible for repeated scans obtained with the same electrode after brief stirring. The glassy carbon electrode was found to be less suitable for oxalic acid oxidation studies because the peaks in the voltammograms were poorly defined and the current response was markedly reduced. These investigations suggest that carbon paste electrodes are sensitive and stable for oxalic acid oxidation studies. A plot of the peak currents obtained with carbon paste electrode for different concentrations of oxalic acid between 1×10^?4M to 1×10^?3M was linear and reproducible. It is suggested that a flow through carbon paste electrode coupled to a chromatographic column can be used in the development of a sensitive method for oxalic acid analysis in biological samples.     

Structure of polypiperylene chain segments according to high-resolution 13C NMR spectra

The microstructure of stereoregular 1,4-trans-and 1,4-cis-polypiperylenes, as well as polymers prepared from the trans-and cis-piperylene isomers via cationic polymerization in the presence of TiCl₄, was studied by high-resolution ¹³C NMR spectroscopy. Polypiperylene synthesized through the cationic polymerization of the cis isomer had a more diversified morphology of the macromolecular chain, i.e., had higher relative amounts of 1,2-cis-units and combinations of irregular-addition 1,4-trans-units. It was shown that ¹³C NMR spectra give the most comprehensive and independent information on the details of structure of the piperylene macromolecular chain.     

Identification and characterization of isomeric N-glycans of human alfa-acid-glycoprotein by stable isotope labelling and ZIC-HILIC-MS in combination with exoglycosidase digestion

In this study, a ZIC-HILIC-MS methodology for the analysis of N-glycan isomers was optimized to obtain greater detection sensitivity and thus identify more glycan structures in hAGP. In a second step, this method was combined with glycan reductive isotope labelling (GRIL) through [¹²C₆]/[¹³C₆]-aniline and exoglycosidase digestion to characterize the different glycan isomers. The GRIL method allows the peak areas resulting from two different labelled samples to be compared, since neither retention time shifts nor variations in the ionization of glycans between these samples are obtained. First, sialic acid linkage assignations were performed for most hAGP glycan isomers with α2-3 sialidase digestion. Bi-, tri- and tetraantennary glycan isomers with different terminal sialic acid linkages to galactose (α2-3 or α2-6) were assigned, and the potential of this technique for the structural characterization of isobaric isomers was therefore demonstrated. Furthermore, fucose linkage isomers of hAGP glycans were also characterized using this isotope-labelling approach in combination with α1-3,4 fucosidase and β1-4 galactosidase digestion. α1-3 antennary fucoses and α1-6 core fucosylation were detected in hAGP fucosylated glycans. These established methodologies can be extremely useful for patho-glycomic studies to characterize glycoproteins of biomedical interest and find novel glycan isomers that could be used as biomarkers in cancer research.     

The synthesis and photochemical properties of amphiphilic phenylazonaphthalenes

Three novel amphiphilic phenylazonaphthalenes, namely, 6-(4-(4-octylphenylazo)naphthoxy)hexanoic acid, 6-(4-(4-dodecylphenylazo)naphthoxy)hexanoic acid, 6-(4-(4-hexadecylphenylazo)naphthoxy)hexanoic acid, were synthesized by diazo coupling, etherification and hydrolysis reactions successively. The kinetic studies of the trans–cis isomerization indicated that about 95% of the trans isomers of these compounds in chloroform solutions were transformed to cis isomers under the irradiation of near-ultraviolet light (380±30 nm) observed from UV–Vis spectra. In the dark condition, the cis isomers could reversibly convert to trans isomers following the first-order kinetics at the rates of 4.9×10^-4, 5.7×10^-4, 7.7×10^-4 S^-1, respectively.     

Voltammetric determination of agriculturally-significant benzenearsonic acids

Direct current and differential pulse polarographic measurements are reported on a series of substituted benzenearsonic acid compounds that are important in agricultural applications. Compounds studied were o-aminobenzenearsonic acid, p-aminobenzene-arsonic acid, p-nitrobenzenearsonic acid, p-ureidobenzenearsonic acid, and 3-nitro-4-hydroxybenzenearsonic acid. Polarographic reduction potentials varied with pH for all compounds, shifting to more negative values as the pH was increased. Although diffusion-controlled reduction waves were observed in all cases, some compounds exhibited a dependence of E$\text{1}\text{2}$ on concentration, especially at relatively high concentrations. Differential pulse polarographic peak currents were proportional to concentration from 10^-4 M to 10^-6 M.     

Rearrangement with oxide ion transfer in reactions of 4-chloro-2-oxo-2,3-dihydrothiazole-5-carbaldehyde with ureas. cis-(Z)-trans-(E) isomerism of N-(2,4-dioxothiazolidin-5-ylidenemethyl)ureas

4-Chloro-2-oxo-2,3-dihydrothiazole-5-carbaldehyde reacted with monosubstituted ureas to give cis-(Z)-and trans-(E)-N-(2,4-dioxothiazolidin-5-ylidenemethyl)ureas via rearrangement involving oxide ion transfer, cis (Z) Isomers were formed in methanol or dimethylformamide, while both individual cis (Z) and trans (E) isomers and their mixtures were isolated in the reaction performed in acetic acid.     

Concise synthesis of AHMHA unit in perthamide C. Structural and stereochemical revision of perthamide C

Diastereomers of 3-amino-2-hydroxy-6-methylheptanoic acid (AHMHA), a new amino acid unit in perthamides C and D, have been synthesized from commercially available 4-methylpentanol in a concise manner and 50% average overall yield. Comparison of the ¹H and ¹³C NMR data, optical rotation data and Marfey’s analysis of the resulting isomers with the natural fragment unambiguously allowed the configurational assignment of the natural residue as (2R,3R). A structural revision of perthamides C and D is also reported.     

A study of shake-up satellites in Co 2p photoelectron spectra of trans-[Co(NH3)4Cl2]Cl and cis-[Co(NH3)4Cl2]Cl isomers

Mg Kα X-ray photoelectron (ESCA) spectra of the Co 2p levels have been obtained in trans- and cis-[Co(NH₃)₄Cl₂]Cl isomers. It is observed that these compounds slowly decompose under X-ray irradiation. A procedure is employed to record real spectra for both the trans and cis isomers without any significant complication by the decomposition products. Three satellites are observed in both spectra at binding energies ≈ 4.8 eV, ≈ 9.3 eV, and ≈ 16.5 eV greater than that of the Co 2p_{$\text{3}\text{2}$} peak. These isomers are distinguished from one another by the sizable difference in the relative intensity of the first satellite to the main peak. The first two satellites are assigned to ligand to Co 3d shake-up transitions by use of symmetry arguments based on molecular orbital theory, while the origin of the third satellite is less certain. The implication of the results is discussed.     

Fourier transform NMR investigations of organotin compounds : VIII. Propenyl- and isopropenyl-tin compounds; detection and identification of isomers using 119Sn and 13c NMR

Starting from the equilibrium mixture of cis- and trans-1-bromo-1-propene, isomeric mixtures of compounds Me_n Sn(CH=GHMe)_4-n (n = 0–3) have been prepared and studied. While proton NMR only allows distinction between the methyltin signals of the various isomers (except where n = 3), the ¹³C spectra show separate signals for almost all isomeric carbons even when n = 0. In the ¹¹⁹Sn spectra the signals due to the various isomers are separated by ca. 20 ppm for a given value of n; the peak areas can be used to estimate the proportions of cis- and trans-propenyl residues present in the mixtures. Addition of 2-bromo-propene to the starting 1-bromo-1-propenes leads to the formation of further isomers, which can in all cases be observed and identified in the ¹¹⁹Sn spectra; ¹¹⁹Sn shifts can be calculated using the shifts for the Me₃SnC₃H₅ isomers as increments.     

Direct determination of bismuth and antimony in sea water by anodic stripping voltammetry

A method based on anodic stripping voltammetry at the mercury-coated graphite electrode has been developed for the direct determination of bismuth and antimony at their natural levels in sea water. Bismuth plated at -0.4 V from sea water made 1 M in hydrochloric acid gives a stripping peak proportional to concentration at -0.2 V without interference from antimony or other metals normally present. Antimony may be plated from sea water made 4 M in hydrochloric acid and gives a stripping peak at -0.2 V proportional to the sum of bismuth and antimony. By use of the standard addition technique, satisfactory results were obtained for sea water samples with concentration ranges of 0.02–0.09 μg kg^?1 for bismuth and 0.2–0.5 μg kg^?1 for antimony.     

HPLC of anions on coated reversed phase columns using indirect UV-detection and eluents containing nitrophthalic acids

Analysis of anions by HPLC has been optimized in the direction of reduced analysis times with standard reversed phase columns and UV detection. This was achieved by use of a new eluent containing 3-nitrophthalic acid and small proportions of acetonitrile. Resin-based and silica-based anion exchangers of varying ion-exchange capacities are prepared with cetyltrimethylammonium bromide by a rapid dynamic coating technique. Some new, strong eluents containing nitrophthalic acids are evaluated and compared with an eluent containing potassium hydrogen phthalate. Addition of acetonitrile was found to improve the retention behavior of mono- and divalent anions. An automatic system was developed for the analysis of chloride, nitrate, and sulfate in drinking water. It is shown that a water sample can be analyzed in less than two minutes on a column of 25 mm length.     

Investigation of the exo and endo isomers of dioxolane-type benzylidene derivatives of carbohydrates by 13C NMR spectroscopy

The absolute configurations of nine 2,3-O-benzylidene-α-L-rhamno- and α-D-mannopyranoside diasteteomeric pairs were determined and the ¹³C NMR spectra of further thirteen α-L-rhamno- and α-D-mannopyranosides, having various substituents, were completely assigned.Four ¹³C shifts were found suitable for the determination of the absolute configuration of the dioxolane skeleton. (1) The chemical shift of the acetal carbon in the endo isomers is between 103.9 and 104.7 ppm whereas for the exo isomers this region extends from 102.8 to 103.4 ppm; (2) The formation of the dioxolane ring causes a deshielding effect for the bridgehead carbons, in the exo isomers this effect is more pronounced for C-3 whereas in the endo isomers for C-2. For C-4, shielding effect was found in the exo isomers and deshielding effect in the endo ones; (3) The chemical shift of the quaternary carbon of the phenyl group is greater in the exo isomers than in the endo ones; (4) The difference between the shift of the acetal carbon and that of the quaternary carbon of the phenyl group in the exo isomers is greater than 35.4 ppm, in the endo isomers is less than 33.7 ppm.     

Separation and quantification of four isomers of indole-3-acetyl-myo-inositol in plant tissues using high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry

Indole-3-acetyl-myo-inositol (IAInos) is one of the most important auxin conjugates for storage and transportation of auxin. The information of its composition, distribution, and metabolism is particularly desired for elucidating the related signal transduction pathways of the plant hormones. However, separation and quantification of the four individual IAInos isomers in plant tissues have not been reported so far. In this work, we first synthesized and isolated four IAInos isomers using semi-preparative high-performance liquid chromatography (HPLC). The IAInos isomer structures were characterized using liquid chromatography-electrospray ionization quadrupole time-of-flight tandem mass spectrometry (LC-QTOF/MS) and nuclear magnetic resonance spectroscopy (NMR). Using these pure compounds as internal or external standards, an efficient LC-MS method was developed for simultaneous detection of indole-3-acetic acid, methyl indole-3-acetic acid ester, and the four IAInos isomers in plant tissue samples. The linear working range and lower limit of detection for the four IAInos isomers are 10–2,000 ng mL^?1 and 5.0 ng mL^?1, respectively. The stabilities and interconversion pathways of IAInos isomers were studied using our synthetic isomers. It was found that two IAInos isomers existed in Zea mays kernels, while all of the four IAInos isomers were present in the roots of Arabidopsis thaliana. The content of IAInos in A. thaliana roots was much lower than in the Z. mays kernels. The methodology in this article provides useful techniques and methods for systematic study on the phytophysiology and phytochemistry of IAA conjugates and other related plant hormones.

Development of Stereoselective Method for the Quantification of Stereoisomers and Geometrical Isomer of Pitavastatin Calcium by Enhanced Approach

A new, simple, selective, and robust normal-phase method for the accurate quantification of all the four stereoisomers and one geometrical isomer of pitavastatin calcium (PIT) in drug substances and drug products was developed. The method is capable of quantifying all the isomers in the presence of other related substances. Separation was achieved using immobilized amylose stationary phase (Chiralpak IA) with a mixture of n-heptane, 1-butanol, methanol, formic acid, and diethylamine. Multivariate analysis and statistical tools were used to develop this highly robust method in a short span of time. A central composite design was employed to study the main effects and interactions of the independent variables. The method exhibited consistent, high-quality recoveries [97.3 ± 1.7 to 99.3 ± 2.1 (mean ± RSD)] with a high precision for all the isomers. Linear regression analysis revealed an excellent correlation between peak responses and concentrations (r ² values of 0.9990–0.9998) for the isomers. The method is sensitive enough to quantify any isomers above 0.02 % and detect any isomer above 0.006 % in PIT. Forced degradation studies proved that the method is specific for isomers. m/z values were determined for the major degradants and their possible structures were proposed on the basis of the known reactivity.     

Differential scanning calorimetry study of charge-transfer complexes of polynuclear aromatic hydrocarbons with the asymmetric acceptors 3- and 4-nitrophthalic anhydride

Charge-transfer, crystalline complexes of 3- and 4-nitrophthalic anhydrides with a number of unsubstituted polynuclear aromatic hydrocabons were studied by differential scanning calorimetry. The 3- and 4-nitrophthalic anhydrides are complexing agents more selective than s.trinitrobenzene and pyromellitic dianhydride, and only form complexes with a few of the twelve hydrocarbons investigated.Under the adopted conditions 3-NPA forms complexes with: pyrene, 3,4-benzopyrene, and 1,2,5,6,-dibenzoanthracene; 4-NPA forms complexes with these hydrocarbons and with anthracene, phenanthrene, 1,2-benzoanthracene benzoperylene, and coronene. Though having an electron affinity close to that of s.trinitrobenzene, 4-NPA forms less stable complexes with the polynuclear aromatic hydrocarbons, due to the asymmetry and non-planarity of its molecule.