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Introduction: Metabolite identification in biological samples using Nuclear Magnetic Resonance (NMR) spectra is a challenging task due to the complexity of the biological matrices. Objectives: This paper introduces a new, automated computational scheme for the identification of metabolites in 1D H NMR spectra based on the Human Metabolome Database. Methods: The methodological scheme comprises of the sequential application of preprocessing, data reduction, metabolite screening and combination selection. Results: The proposed scheme has been tested on the 1D H NMR spectra of: (a) an amino acid mixture, (b) a serum sample spiked with the amino acid mixture, (c) 20 blood serum, (d) 20 human amniotic fluid samples, (e) 160 serum samples from publicly available database. The methodological scheme was compared against widely used software tools, exhibiting good performance in terms of correct assignment of the metabolites. Conclusions: This new robust scheme accomplishes to automatically identify peak resonances in H-NMR spectra with high accuracy and less human intervention with a wide range of applications in metabolic profiling. [ABSTRACT FROM AUTHOR]

The taxonomical classification among fungi kingdom in the last decades was evolved. In this work the targeted metabolomics study based on H NMR spectroscopy combined with chemometrics tools was reported to be useful for differentiation of three model of fungal strains, which represent various genus of Ascomycota ( Aspergillus pallidofulvus, Fusarium oxysporum, Geotrichum candidum) were selected in order to perform metabolomics studies. Each tested species, revealed specific metabolic profile of primary endo-metabolites. The species of A. pallidofulvus is represented by the highest concentration of glycerol, glucitol and Unk5. While, F. oxysporum species is characterised by increased level of propylene glycol, ethanol, 4-aminobutyrate, succinate, xylose, Unk1 and Unk4. In G. candidum, 3-methyl-2-oxovalerate, glutamate, pyruvate, glutamine and citrate were elevated. Additionally, a detailed analysis of metabolic changes among A. pallidofulvus, F. oxysporum and G. candidum showed that A. pallidofulvus seems to be the most pathogenic fungi. The obtained results demonstrated that targeted metabolomics analysis could be utilized in the future as a supporting taxonomical tool for currently methods. Graphical Abstract: [ABSTRACT FROM AUTHOR]

The reaction of 2,2-bis(methoxy-NNO-azoxy)ethanol nitrate with pyrazole, 3-nitropyrazole, 4-nitropyrazole, or 3,4-dinitropyrazole allowed to obtain the respective N-[2,2-bis(methoxy-NNO-azoxy)ethyl]pyrazoles. In the case of 3-nitropyrazole, only the 3-nitro isomer was formed, while alkylation of 3,4-dinitropyrazole led to a mixture of 3,4- and 4,5-dinitro isomers in 7:1 ratio, which was difficult to separate. The obtained pyrazoles were characterized by H, C, and N NMR spectroscopy. X-ray structural studies were performed for the synthesized 3-NO, 4-NO, and 3,4-(NO) derivatives. [ABSTRACT FROM AUTHOR]

Here, we report a novel approach to enumeration of carboxylic groups carried by individual molecules of humic substances using selective chemical modification and isotopic labeling (deuteromethylation) and high-resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FTICR MS). Esterification was conducted with a use of thionyl chloride-deuteromethanol reagent under mild conditions to avoid transesterification. The deuteromethylated products were subjected to solid phase extraction using PPL Bond Elute cartridges prior to FTICR MS analysis. An amount of carboxyl groups in the individual molecular component was estimated from the length of identified deuteromethylation series. The method allowed for discerning between compounds with close elemental compositions possessing different protolytic properties. We found that different carboxylic moieties occupy distinct regions in molecular space of humic substances (HS) projected onto Van Krevelen diagram. These locations do not depend on the source of the humic material and can be assigned to carboxyl-rich alicyclic molecules (5 to 6 COOH), hydrolyzable tannins (3-4 COOH), lignins (1 to 2 COOH), condensed tannins and lignans (0 to 1 COOH), and carbohydrates (0 COOH). At the same time, the alignment pattern of these carboxylated species along the structural evolution lines in Van Krevelen diagrams was characteristic to the specific transformation processes undergone by the humic materials in the different environments. The obtained data enable mapping of molecular ensemble of HS with regards to their specific acidic compartments and might be used for directed fractionation of HS. [ABSTRACT FROM AUTHOR]

Spectral (H NMR and IR), optical, and voltammetry parameters of Pd(II), Pt(II), Rh(III), and Ir(III) complexes with ethylenediamine and metallated azole luminophors [2-phenylbenzoxazole, 2-phenylbenzothiazole, 2,5-diphenyloxazole, 2-(1,1'-biphenyl)-4-yl]-5-phenyloxazole, and 2-(naphthalene-l-yl)benzothiazole] have been studied. The variation in spectroscopic parameters of the complexes is related to the increase in the efficiency of donor-acceptor interaction of Pt(II) and Ir(III) with the ligands as compared to Pd(II) and Rh(III). The correlation between the energy of the metal-ligand charge transfer bands and the difference between the single-electron oxidation and reduction potentials of the complexes is observed. Quenching of the fluorescence of metallated azoles and phosphorescence of the complexes in the visible region from the metal-modified intraligand excited state are related with the increase in the efficiency of the singlettriplet conversion due to the spin-orbital interaction in platinum metals. [ABSTRACT FROM AUTHOR]

According to the data of H NMR spectroscopy, trans-hydroxochloro complexes containing from two to four pyridine molecules in the internal sphere are formed on the heating of a dilute aqueous solution of K[Ru(NO)Cl] with pyridine. The evaporation of the reaction solution with concentrated hydrochloric acid gives fac-[Ru(NO)(Py)Cl] ( I) in a yield of ~90%. The structures of two crystalline modifications of this complex are determined by X-ray diffraction analysis (CIF files ССDС nos. 1452208 ( Ia) and 1452207 ( Ib)). IR spectroscopy shows that the irradiation of complex I (λ ~ 450 nm, T = 80 K) results in photoisomerization with the formation of the metastable state MS1 in which the nitroso group is coordinated by the oxygen atom. The activation parameters of the photoisomerization are determined from the data of differential scanning calorimetry (DSC). Compound trans-[Ru(NO)Py(OH)]Cl ∙ HO is isolated in a yield of ~70% on reflux of complex I with a pyridine excess in an aqueous solution, and the presence of molecules of water of crystallization in this compound is confirmed by thermal gravimetry (TG) and IR spectroscopy. [ABSTRACT FROM AUTHOR]

The influence of water-dimethylsulfoxide (HO-DMSO) solvent on the reaction of the molecular complex formation between cryptand [2.2.2] (L) and glycyl-glycyl-glycine (3Gly) was studied at T = 298.15 K. The thermodynamic parameters for the reaction (lg K , Δ G , Δ H , TΔ S ) were obtained from calorimetric titration experiments carried out by means of the calorimetric system TAM III (TA Instruments, USA). The binding mode of 3Gly-L complexation in HO-DMSO solvent was determined by NMR spectroscopy, and the spectroscopic data were also used to calculate the [3GlyL] stability constants. A slight increase in complex stability and reaction exothermicity was observed at increasing DMSO content. The thermodynamic parameters for [3GlyL] are compared with thermodynamic parameters of complex formation of 18-crown-6 with amino acids and 3Gly in mixed solvents using the solvation-thermodynamic approach. [ABSTRACT FROM AUTHOR]

The results of H NMR and quantum chemical studies of hydrolysis of isobutylaluminum aryloxides are presented. According to the data of H NMR spectroscopy, the hydrolysis of monomeric diisobutylaluminum aryloxides (2,6-Bu -CHO)AlBu and (2,6-Bu ,4-Me-CHO)AlBu occurs selectively at the Al-OAr bond to form the corresponding sterically bulky phenol and polyisobutylaluminoxane. At the molar ratios Al: HO = 2, the formed sterically bulky phenol reacts slowly with diisobutylaluminum monoaryloxide to form isobutylaluminum diaryloxide. Dimeric aryloxide [(2-Bu-CHO)AlBu ] is not hydrolyzed under similar conditions. The quantum chemical calculations confirmed the experimental results: the hydrolysis at the Al-OAr bond has a lower energy barrier than that at the Al-C bond because of the formation of $${H_{{H_2}O}} \ldots {O_{O - Ar}}$$ hydrogen bonds. [ABSTRACT FROM AUTHOR]

Amethod for determining molar substitution of hydroxyethylstarches by H NMR spectroscopy was validated in terms of specificity, linearity, correctness, precision, and range of application. The method can be used to evaluate the parameter 'molar substitution' in the framework of pharmacological expert assessment of hydroxyethylstarches as components of medicines. [ABSTRACT FROM AUTHOR]

The metabolic profiling of the rat liver was carried out in order to estimate the efficiency of proton nuclear magnetic resonance (H NMR) spectroscopy as a method of metabolomic phenotyping and a method of detecting early metabolic changes during toxic effects. The tissue samples were taken from three groups of rats: group C, control animals; group A, animals that repeatedly received 15% alcohol solution (its intake induced no pathological liver changes, but stimulated the proliferation of the hepatocytes); and group A + R, alcohol in combination with the plant hepatoprotective Reishi preparation ( Ganoderma lucidum). As follows from the results obtained, the changes in the metabolite concentration in liver (observed in group A) reflected the typical metabolic reaction to the alcohol intake and were expressed in a decrease in the content of glycine, leucine, isoleucine, valine, choline, and lactate, as well as in an increase in the TMAO level. The concentration of glycine, valine, and TMAO was restored in the rats of group A + R during the Reishi intake. In addition, an increase in the concentrations of NAD, ATP, UTP, succinate, pyranose, and acetate was registered in group A + R relative to the control. Individual variations in the content of valine, isoleucine, leucine, lactate, choline, and pyranose is correlated to the number of binuclear hepatocytes (as an indicator of proliferative activity). Thus, the study of liver tissues by H NMR spectroscopy method allows us to detect early deviations in the level of metabolites during chronic consumption of small alcohol doses and can be a promising approach both for diagnostic detection of alcoholic liver damage and for estimation of the efficiency of the applied drug therapy. [ABSTRACT FROM AUTHOR]

Isobutylalumoxanes have been obtained by hydrolysis of triisobutylaluminium (TIBA) with water in the form of vapour ( 1) or ice particles ( 2) at Al/HO = 2 mol/mol. H NMR spectra of hydrolyzates showed the presence of unreacted TIBA indicating the formation of alumoxanes larger than BuAl- O-AlBu which one can expect based on the molar ratio of reagents. Alumoxanes 1 and 2 demonstrate high activating ability for rac-Et(2-MeInd)ZrMe in copolymerization reactions of ethylene with propylene and terpolymerization of ethylene with propylene and 5-ethylidene-2-norbornene. Alumoxane 1 demonstrates high structural and chemical stability during long-term storage (for 1 year) that results in consistent activating ability and similarity of molecular weight characteristics of polymer formed. Alumoxane 2 is much less structurally stable which is manifested in considerable changes of H NMR spectra of the product even after several days of storage. It essentially loses activating ability after 3 months' storage. The alumoxanes with high activating ability have been also obtained by in situ TIBA hydrolysis with water intentionally incorporated into toluene (~1 × 10 mol/l) prior to polymerization also at Al/HO = 2 mol/mol. The differences of catalytic systems with different activators are also reflected in differences in microstructure, molecular-weight, thermal-physical characteristics and physical-mechanical properties of copolymers formed. [ABSTRACT FROM AUTHOR]

Features of Z→ E isomerization of ethyl α-nitrocinnamates as well as their furyl and thienyl heteroanalogs depending on the nature of the substituent in the β-position of α-nitroacrylates, deuterated solvent and duration of exposure of the sample were studied by means of H NMR spectroscopy. [ABSTRACT FROM AUTHOR]

The novel method for the peptide pharmacokinetics in tissues of laboratory animals was elaborated by the example of the HLDF-6 peptide amide. This method practically completely prevented the proteolytic degradation of peptides in the course of the analysis. The HLDF-6 hexapeptide (TGENHR) is a fragment corresponding to the 41-46 sequence of the human leukocyte differentiation factor (HLDF). It exhibits a wide spectrum of nootropic and neuroprotective activity. Therapeutic agents for prevention and therapy of cerebrovascular and neurodegenerative diseases have been created on the basis of the HLDF-6 amide (TGENHR-NH). Pharmacokinetics and the molecular mechanism of action of the HLDF-6 peptide amide were studied using its tritium-labeled and deuterium-labeled derivatives. The labeled peptides were prepared with the use of the high-temperature solid-state catalytic isotope exchange reaction (HSCIE). The tritiumlabeled [H]TGENHR-NH peptide was obtained with a molar radioactivity of 230 Ci/mmol. The deuteriumlabeled [H]TGENHR-NH peptide was prepared with an average deuterium incorporation of 10.5 atoms per the one peptide molecule. The NMR spectroscopy confirmed a uniform distribution of the isotope label throughout the whole peptide molecule. This uniformity allowed a qualitative analysis of both the peptide itself and all the possible fragments of its biodegradation in the organism's tissues. The main TGENHR-NH metabolites which were formed during its proteolytic cleavage in the blood plasma were quantitatively analyzed and pharmacokinetics of the peptide amide was investigated with the use of its tritium-labeled derivative after intravenous and intranasal administration in mice, rats, and rabbits. Values of the basic pharmacokinetic parameters were calculated, the hypothesis of pharmacokinetic linearity was checked, and metabolism of the peptide was studied on the basis of the obtained pharmacokinetic profiles of TGENHR-NH. The TGENHR-NH peptide was shown to have extremely high bioavailability with its intranasal administration (34% for rats). The peptide was quickly disappeared from blood due to its active proteolytic degradation in organism's tissues. The TGENHR-NH peptide was shown to be highly stable towards the proteolytic hydrolysis during its incubation with the blood plasma, and a quantitative analysis of the formed metabolites was performed. [ABSTRACT FROM AUTHOR]

The mechanism of formation of resinous compounds during use of industrial and motor oils was studied by IR and NMR spectroscopy. Based on a comparative analysis of the spectra of samples of the used oil and the resins separated from it and the spectrum of fresh oil it was concluded that, besides oxidative mechanism, resinous compounds are formed in the oils as a result of oligomerization of the hydrocarbons. The molecules of the latter suffer, in the thermomechanical deformation process, profound stereostructural change at the level of distortion of the torsion angles and bond lengths. This leads to increase of the potential energy, corresponding dissociation of the R-C⋯H bonds in the hydrocarbons, and increase of their acidity, which stimulates oligomerization at these protonated bonds, i.e., initiates the oligomerization process and formation of aromatic hydrocarbons, or aging of the oil. The distortion of the stereostructure of the hydrocarbons in the oil during use remains in the mechanochemical memory of the molecules. This is why the purified used oil, even without oxidation of the hydrocarbons, becomes dark during storage because of the chromophoric -C-H acids that are formed. The latter are neutralized in the presence of alkaline reagents. [ABSTRACT FROM AUTHOR]

Variations in sample collection, processing and storage within the field of clinical metabolomics might hamper its effective implementation. In this study, the impact of relevant preanalytical conditions on the plasma H NMR metabolic profile was examined. The biobanking community recently developed a method for coding preanalytical conditions called the Standard PREanalytical Code (SPREC). It is envisaged that SPREC will ultimately identify which samples are fit for a particular analysis, based on prior validation by a panel of experts in the respective field. In an effort to validate SPREC for H NMR plasma metabolomics, we have coded the conditions used here, when possible, according to SPREC and evaluated its power to identify preanalytical conditions that affect the plasma H NMR metabolic profile. From all preanalytical conditions studied, only prolonged processing delays (3 and 8 h) have a significant impact on the plasma H NMR metabolic profile as compared to the reference condition (30 min). Principal component analysis shows a clear systematic shift as a function of increasing processing delay. Nevertheless, the inter-individual variation is clearly much larger than this preanalytical variation, indicating that the impact on multivariate group classification will be minimal. Nonetheless, we recommend to keep the time gap between blood collection and centrifugation similar for all samples within a study. The implementation of SPREC within clinical metabolomics allows for an appropriate sample encoding and exclusion of samples that were subjected to unwanted, interfering preanalytical conditions. Without doubt, it will contribute to the validation of H NMR metabolomics in clinical, biobank and multicenter research settings. [ABSTRACT FROM AUTHOR]

The influence of water-acetone (HO-MeAc) and water-dimethylsulfoxide (HO-DMSO) solvents on the reaction of the molecular complex formation between 18-crown-6 ether (18C6) and small peptide triglycine (3Gly) has been studied at T = 298.15 K. The thermodynamic parameters for the reaction (lg K, Δ G, Δ H, Δ S) were obtained from calorimetric titration experiments carried out by means of the calorimetric system TAM III (TA Instruments, USA). The binding mode of 3Gly-18C6 complexation in HO-MeAc and in HO-DMSO solvents was determined by H NMR spectroscopy, and the spectroscopic data were also used to calculate the [3Gly18C6] stability constants. The increase in MeAc and DMSO concentrations in solvents results in an increase in the [3Gly18C6] complex stability and in the exothermicity of complexation. The thermodynamics of the [3Gly18C6] molecular complex formation is discussed in comparison with thermodynamic parameters of complex formation between 18C6 and amino acids in mixed solvents using the solvation-thermodynamic approach. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE) is a severe neuropsychiatric complication due to acute or chronic liver failure. In this work, an acute thioacetamide induced HE mice model was established to investigate the metabolic events in the onset of HE (OHE) and the protective role of taurine (TAU). Sera for biochemical evaluation, and livers and cortexes for histopathological inspection and NMR-based metabolomic investigation were collected. Principal component analysis and orthogonal partial least squares-discriminant analysis were performed to excavate differential metabolites of OHE, and explore the protective role of TAU. Metabolites pathway analysis was performed on significant metabolites selected based on loading/S-plots and fold change plots to identify biologically meaningful metabolic patterns and relevant pathways. The most affected pathways in OHE mice were those along the liver-brain axis: among them, the alanine, aspartate and glutamate metabolism was the most important. TAU showed better performance in improving the disturbed metabolism in the cortex than in the liver of OHE mice. This pilot study based on metabolomics approach and pathway analysis should help to understand HE systematically, and to develop new therapy for HE. [ABSTRACT FROM AUTHOR]

The hydration of systems obtained via the adsorption of alkali metal chlorides on A-300 nanosilica is studied by means of low-temperature H NMR spectroscopy. It is shown that in weakly polar organic media, adsorbed water is present in the form of weakly and strongly associated water. A reduction in the differentiation of adsorbed water in the SiO/NaCl > SiO/KCl > SiO/LiCl series of composites is established that could be due to changes in the lattice parameters of SiO. Quantum-chemical calculations are performed for the H NMR spectra of complexes containing clusters of SiO(OH) and hydrated ion pairs of alkali metal chlorides. These calculations allow us to explain the displacement in the chemical shifts of water protons. [ABSTRACT FROM AUTHOR]

Temperature-induced collapse of hydrogels of interpenetrating polymer networks (IPNs) poly( N-vinylcaprolactam)/poly( N-isopropylacrylamide) (PVCL/PNIPAm) and poly( N-isopropylmethacrylamide) (PNIPMAm)/PNIPAm, where both components are thermoresponsive, was studied by combination of H nuclear magnetic resonance (NMR) spectroscopy, small-angle neutron scattering (SANS), differential scanning calorimetry (DSC), and dynamic mechanical measurements. Behavior of studied hydrogels (one or two transitions) was found to depend on the ratio of both IPN components. For hydrogels of IPNs containing around 50 mol% of PNIPAm monomer units, separate transitions were revealed for both components. From SANS curves, it follows that compact three-dimensional multi-chain globules are formed in PNIPMAm/PNIPAm and PVCL/PNIPAm IPN hydrogels at temperatures above the phase transition, with a gyration radius of 14-28 nm. A certain portion of spatially restricted bound water (HDO) was established for all the studied IPNs at temperature above the volume phase transition from measurements of H NMR spectra, spin-spin relaxation times ( T), and diffusion coefficients ( D) of HDO. Slow exchange regime between bound and free water was revealed. Spin-spin relaxation times ( T) and diffusion coefficients ( D) as obtained for the bound HDO are up to 2 orders of magnitude smaller in comparison with 'free' HDO. Higher content of bound water as found for collapsed hydrogels of IPN PVCL/PNIPAm in comparison with PNIPMAm/PNIPAm hydrogels is in accordance with swelling experiments and lower values of the shear mechanical modulus; this shows the decisive role of bound water in this respect. [ABSTRACT FROM AUTHOR]

The binary composite ionic liquid mixtures composed of 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF]) and 1-butyl-3-methylimidazolium acetate ([bmim][Ac]) were studied and used in electroreduction of nitrobenzene for the first time. H NMR and Fourier transform infrared (FTIR) spectroscopy were carried out to acquire a deep understanding of the interaction of binary ionic liquids, and UV/Vis spectroscopy was used to study the interaction between the mixture of ionic liquids and nitrobenzene. It was found that chemical shifts of all protons were changed and significant changes in the anion IR bands were induced, and the UV maximum absorption wavelength and absorbance of nitrobenzene in binary ionic liquids were different from those in the neat ionic liquid. The electrochemical reduction behavior of nitrobenzene in binary composite ionic liquids on platinum electrode was studied by cyclic voltammetry, in situ Fourier transform infrared spectroscopy, and constant potential electrolysis. Results indicated that the reduction of nitrobenzene in binary composite ionic liquids demonstrated higher current densities with a more positive potential, and the product (azobenzene) showed higher yield and selectivity in the composite ionic liquids than in the neat ionic liquids; the concentrations of water in the binary mixtures of ionic liquids had great effect on the electrochemical behavior of nitrobenzene. In the end, the mechanism of reduction of nitrobenzene in binary mixtures of ionic liquids was discussed. [ABSTRACT FROM AUTHOR]

Reactions of [1,2-bis(diphenylphosphino)ethane](hydrido)[hydrotris(pyrazolyl)borato]-ruthenium with proton donors were studied by IR and H NMR spectroscopy in CHCl over a wide temperature range. Dihydrogen bonding to CFCHOH was detected; its spectral and thermodynamic parameters (Δ H° =-3.3±0.2 kcal mol, Δ S° =-6.7±0.6 cal mol K) were determined. The basicity factor E of the hydride ligand is 0.81. The H⋯H distance in the dihydrogen-bonded complex (2.05 Å) was estimated from the changes in the spin-lattice relaxation time T of the hydride resonance. Comparison of the results obtained with the literature data revealed a correlation between the length and enthalpy of formation of the dihydrogen bond as well as a correlation between the basicity of the hydride ligand and the tendency of the fragment [ML] toward stabilization and oxidative addition of H. [ABSTRACT FROM AUTHOR]

The relaxation time, T, of deuterium nuclei in a few deuterated compounds, such as methanol- d, benzene- d, and dimethylsulfoxide- d, is measured at higher temperatures in the range from 300 to 375 K. An almost linear increase in time, T, over an increase in temperature is observed in all these cases, which confirms an increase in the mobility of molecules and a decrease in the correlation time. A T value in the range from 2 to 3 s can be expected for deutrons in small organic molecules at temperatures above 350 K. Thus, a linewidth of about 0.1 Hz in H NMR spectra can be obtained for a magnetic field inhomogeneity of about 0.5 Hz in 1H NMR spectra. Such high resolution H NMR spectra provide information about chemical shifts and J(H-D) spin-spin coupling constants (or J(H-H) = (γ/γ) J(H-D) when the isotope effects on the spin-spin coupling constants are neglected), including information about coupling constants between magnetically equivalent protons that can not be observed in H NMR spectra. New or refined data on the coupling constants are obtained from the studied H NMR spectra for ethanol, propanol, 1,2-dichloroethane, and 1,4-dioxane. [ABSTRACT FROM AUTHOR]

The reactions of tert-butyl hydroperoxide and 1,1,3-trimethyl-3-(4-methylphenyl)butyl hydroperoxide with tetraalkylammonium bromides (AlkNBr) in various solvents were studied by NMR spectroscopy. The formation of a complex between a hydroperoxide molecule and quaternary ammonium salt was experimentally proved. The equilibrium constants for hydroperoxide-AlkNBr complex formation ( K) were determined. The influence of water on the parameters of the H NMR spectrum of tert-butyl hydroperoxide was studied. [ABSTRACT FROM AUTHOR]

The aim of the present work was to study the physicochemical properties of a new compound with kappa-opioid agonist activity, RU 1205, and to develop methods for qualitative and quantitative analysis of RU 1205 substance. Studies were performed using IR, UV, and H NMR spectroscopy, high-performance liquid chromatography, gas-liquid chromatography, and acid-base titration in non-aqueous medium. [ABSTRACT FROM AUTHOR]

Direct experimental confirmation of the formation of ion-molecular associates of (5,10,15,20-tetraphenyl-21H,23H-porphinato)silver(II) (AgTPP) with solvent protons in CFCOOH is obtained by means of 1H NMR spectroscopy. Their structure and spectral properties, as well as the kinetics of dissociation on metal-nitrogen bonds, depending on the concentration of CFCOOH (89-100%) and temperature (298-328 K), are studied It is shown that AgTPP acts as a C-base during the formation of H+ associates, the coordination centers of which have a high stability. [ABSTRACT FROM AUTHOR]

The state of water in partially destroyed dry yeast cells has been studied using low-temperature H NMR spectroscopy. It has been shown that the residual water is in the form of clusters of strongly and weakly associated water (SAW and WAW, respectively). Three or more types of SAW different in the chemical shift values have been found. It has been established that the interfacial water poorly dissolves hydrochloric and trifluoroacetic acids as well as DMSO and CDCN. Hydrochloric acid on a surface of biomaterials can be separated into HCl and water. This process is stabilized by polar co-solvents (DMSO and CDCN) added to the CDCl dispersion medium. [ABSTRACT FROM AUTHOR]

Eight hydrochlorides of 3-{2-[(2/4-fluorophenoxy)-ethylamino]}-2-hydroxypropyl-4-alkoxybenzoates and four hydrochlorides of 3- tert-butylamino-2-hydroxypropyl-4-butoxybenzoates were prepared as potential antagonists of the β-adrenergic receptor (beta-blockers). A multistep synthesis of these compounds is described as well as their detailed analytical characterization. The pharmacokinetic properties of these weak base compounds are significantly influenced by their acid-base dissociation constant, p K. The knowledge of this value is crucial for new drug development. This paper is aimed at developing a methodology that utilizes pH-dependent H NMR spectroscopy for its routine analysis. The selected predicted physico-chemical parameters of the new (arylcarbonyloxy)aminopropanols ( i.e., aryloxyaminopropanol derivatives) were compared with the model drugs esmolol and flestolol. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Elemental analysis, molecular mass, and H NMR data are presented for vacuum residue asphaltenes and the products of vacuum residue hydroconversion in the presence of nanosized MoS catalyst particles obtained 'in situ' in the hydrocarbon medium. Structural group analysis of average asphaltene molecules has been performed and their structural units have been described. The main trends of change in the structural parameters of the molecules under the hydroconversion conditions and the effect of temperature on the character of these changes have been revealed. [ABSTRACT FROM AUTHOR]

The Diels-Alder reaction as a click reaction strategy is applied to the preparation of well-defined polycarbonate (PC)-block copolymers. A well-defined α-anthracene-terminated polycarbonate (PC-anthracene) is prepared using 9-anthracene methanol as an initiator in the ring opening polymerization of benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate in CH2Cl2 at room temperature for 5 h. Next, a well-defined α-furan protected maleimide-terminated-poly(ethylene glycol) (PEG11-MI or PEG37-MI), -poly(methyl methacrylate) (PMMA26-MI), and -poly(ε-caprolactone) (PCL27-MI) were clicked with the PC-anthracene at reflux temperature of toluene to yield their corresponding PC-based block copolymers (PC- b-PEG, PC- b-PMMA, and PC- b-PCL). The homopolymer precursors and their block copolymers were characterized by using the GPC, NMR and UV analysis. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013 [ABSTRACT FROM AUTHOR]

The biologically active conformation of N-(6-phenylhexanoyl)glycyl-tryptophan amide (GB-115), a highly active cholecystokinin-4 retro dipeptide analogue with the anxiolytic activity, has been studied using the conformational analysis by H NMR spectroscopy in solution and the method of sterically restricted analogues. A study of the relationship between the preferable conformation in solution and the anxiolytic activity in the series of GB-115 derivatives showed that the biologically active conformation of this compound is the β-turn. Based on the data on the nuclear Overhauser effect H NMR spectroscopy, this structure was identified as the β-turn of type II. Subsequent synthesis and study of the pharmacological activity of novel sterically restricted analogues of dipeptide GB-115: (2 S)-2-{(3 R)-3-[(6-phenylhexanoyl)amino]-2-oxopyrrolidine-1-yl}-3-(1 H-indole-3-yl)propionic acid ethyl ester, N-(6-phenylhexanoyl)glycyl- N-methyltryptophan ethyl ester, (2 S)-2-[(10,11-dihydro-5 H-dibenzo[ b, f]azepin-5-ylcarbonyl)amino]-3-(1 H-indole-3-yl)propionic acid methyl ester, and (2 S)-2-[({3-[(ethoxycarbonyl)amino]-10,11-dihydro-5 H-dibenzo[ b, f]azepin-5-yl}carbonyl)amino]-3-(1 H-indole-3-yl)propionic acid methyl ester confirmed that the β-turn of type II is the active conformation of GB-115. [ABSTRACT FROM AUTHOR]

The solvation state of nicotinamide in water-ethanol solvent is investigated by means of H and C NMR spectroscopy. It is found that the nitrogen heteroatom is resolvated at x = 0.05-0.25. The resolvation boundary of the silver(I) ion is determined by nuclear magnetic relaxation. The relationship between the structural and thermodynamic characteristics of the solvation of nicotinamide and the silver(I) ion is demonstrated. [ABSTRACT FROM AUTHOR]

Oriented stratum corneum model lipid membranes were used to study the influence of the short chain ceramides (CER)[NP] and [AP] as well as the impact of the lipophilic penetration enhancer molecules oleic acid (OA) and isopropyl myristate (IPM) on the lipid nanostructure. The influence of the enhancer molecules were studied using specifically deuterated OA and IPM and neutron diffraction. H NMR spectroscopy was used to study the impact of the ceramides' degree of order within the stratum corneum model lipid membranes. It was found that CER[NP] forms two very stable phases with high resistance against temperature increase. Phase B showed unusual hydration behavior as no water uptake of this phase was observed. The H NMR spectroscopic measurements showed that CER[NP] based ternary model system had a higher state of lamellar order in comparison to CER[AP] based lipid matrix. The studies confirmed that the short chain ceramides, particularly CER[NP], have a very high impact on the integrity of the Stratum corneum lipid bilayers. The penetration enhancer OA has not influenced the repeat distance of the model membrane based on CER[AP], and was not able to induce a phase separation in the investigated lipid matrix. However, a disorder and a fluidisation of the model membranes were observed when OA was incorporated. IPM showed the same effect but two phases (assigned as phase A and B) appeared, when IPM was used as penetration enhancer and incorporated into the model membrane. Furthermore, two arrangements of IPM were identified in phase A using deuterated IPM. A model of the nanostructure of the Stratum corneum lipid membranes is presented. [ABSTRACT FROM AUTHOR]

Isobutylalumoxanes of different composition were synthesized by the hydrolysis of triisobutylaluminum (TIBA) with crystalline hydrate CuSO·5HO and water taken as cooled ice or as vapor. The composition of the formed alumoxanes and the degree of water participation in their formation was monitored by H NMR. The hydrolysis of TIBA on CuSO·5HO is rather selective method of synthesis of alumoxanes. The synthesized alumoxanes were used for the activation of dimethylated zirconocenes rac-MeSi(2-Me,4-PhInd)ZrMe and rac-Et(2-MeInd)ZrMe in propylene polymerization at the molar ratios Al/Zr = 50-750. It was concluded that the hydrolysis afforded several products with different structures and different activating ability. The systems with oligomeric forms of isobutylalumoxanes, especially those obtained by TIBA hydrolysis with water, showed the highest activity. [ABSTRACT FROM AUTHOR]

E5 is a 20-residue-long analog of the fusion peptide from influenza hemagglutinin (GLFEAIAEFIEGGWEGLIEG). It has been suggested that two of its five glutamates, Glu11and Glu15, are critical in its pH-dependent membrane perturbation. To reveal their specific involvement, a pair of analogs with substitution of either Glu11 or Glu15 for Ala were synthesized. By analysis of the pH-dependence of the chemical shifts of protons of these peptides bound to dodecylphosphocholine micelles we found: (1) the peptides adopt an amphiphilic alpha-helical structure within residues 2-18, similar to the parent peptide; (2) the helix is significantly more disordered at neutral pH than at acidic pH for E5 peptide only; and (3) in E5 and mutant peptides the Glu11 and 15 residues have similar p K values, higher than those of the other glutamates. This excludes their mutual interaction in E5, being a source of the elevated p K values. We attribute this phenomenon to the presence of minor states caused by deepening of the Glu11 and 15 side-chains in the hydrophobic environment of the membrane. As the mid-pH of membrane-perturbation activity of E5 matches the p K value of these glutamates, we conclude their presence contributes to the plasticity of the peptide and determines the pH-dependence of membrane perturbation caused by E5. [ABSTRACT FROM AUTHOR]

Combination of H NMR spectroscopy and differential scanning calorimetry (DSC) was used to investigate temperature-induced phase transition in DO solutions of poly( N-isopropylmethacrylamide- co-acrylamide) random copolymers. Both the NMR and DSC data showed dependence on the acrylamide (AAm) content in the copolymer; with increasing AAm content, the phase transition is shifted to higher temperatures, and both phase-separated fractions determined by NMR and change of the enthalpy determined by DSC decrease faster than the content of thermosensitive N-isopropylmethacrylamide (NIPMAm) units in the copolymer. NMR data were used to construct van't Hoff plots, and changes of the enthalpy Δ H and entropy Δ S, characterizing the phase transition, were determined. As it follows from comparison of NMR and DSC thermodynamical parameters (Δ H values), the size of the cooperative units (domains), undergoing the transition as a whole, decreases with increasing AAm content in the copolymer since the NIPMAm collapsed domains are separated by regions with hydrated AAm and surrounding NIPMAm sequences. [ABSTRACT FROM AUTHOR]

The metabolomic approach has been widely used in toxicology to investigate mechanisms of toxicity. To understand the mammalian system's response to nickel exposure, we analysed the NiCl induced metabolomic changes in urine of rats using H nuclear magnetic resonance (H NMR) spectroscopy together with clinically relevant biochemical parameters. Male Sprague-Dawley rats were administered intraperitoneally with NiCl at doses of 4, 10 and 20 mg/kg body weight. Urine samples were collected at 8, 16, 24, 72, 96 and 120 h post treatment. The metabolomic profile of rat urine showed prominent changes in citrate, dimethylamine, creatinine, choline, trimethylamine oxide (TMAO), phenyl alanine and hippurate at all doses. Principal component analysis of urine H NMR spectra demonstrated the dose and time dependent development of toxicity. The metabolomic time trajectory, based on pattern recognition analysis of H NMR spectra of urine, illustrated clear separation of pre and post treatments (temporal). Only animals treated with a low dose of NiCl returned to normal physiology. The H NMR spectral data correlated well with the clinically relevant nephrotoxic biomarkers. The urinary metabolomic phenotyping for NiCl induced nephrotoxicity was defined according to the predictive ability of the known metabolite biomarkers, creatinine, citrate and TMAO. The current approach demonstrates that metabolomics, one of the most important platform in system biology, may be a promising tool for identifying and characterizing biochemical responses to toxicity. [ABSTRACT FROM AUTHOR]

The reaction of diphenyl chlorophosphate with the 4-nitrophenolate ion was studied in the presence of a series of para derivatives of pyridine 1-oxide under inverse phase transfer catalysis (IPTC) conditions. The reaction proceeds due to the formation of an ionic intermediate in the organic phase, namely, 1-(diphenoxyphosphoryl) oxypyridinium salts. This conclusion was indicated by both H NMR and IR spectroscopy. [ABSTRACT FROM AUTHOR]

A protocol for determination of oxidation susceptibility of serum lipids based on proton nuclear magnetic resonance (H NMR) spectroscopy is presented and compared to the commonly used spectrophotometric method. Even though there are methodological differences between these two methods, the NMR-based oxidation susceptibility correlates well ( r = 0.73) with the lag time determined spectrophotometrically. In addition to the oxidizability of serum lipids, the NMR method provides also information about the lipid profile. The NMR oxidation assay was applied to the chocolate study including fasting serum samples ( n = 45) from subjects who had consumed white (WC), dark (DC) or high-polyphenol chocolate (HPC) daily for 3 weeks. The oxidation susceptibility of serum lipids decreased in the HPC group, and there was a significant difference between the WC and HPC groups ( P = 0.031). According to the random forest analysis, the consumption of the HPC chocolate induced changes to the amounts of HDL, phosphatidylcholine, sphingomyelin, and nervonic, docosahexaenoic and myristic acids. Furthermore, arachidonic, docosahexaenoic, docosapentaenoic and palmitic acids, gamma-glutamyl transferase, hemoglobin, HDL, phosphatidylcholine and choline containing phospholipids explained about 60% of the oxidation susceptibility values. [ABSTRACT FROM AUTHOR]

The development of techniques allowing the culturing of primary mammalian hepatocytes has provided great insights into liver physiology. For most applications, it is desirable for hepatocytes in culture to mimic hepatocytes in vivo. We used stable isotope resolved metabolomics (SIRM) to assess glucose and glutamine utilization in primary rat and human hepatocytes maintained in standard culture media. Primary rat hepatocytes readily metabolized C-glucose and C-glutamine made evident by C incorporation into glycogen, glycolytic end products, and Krebs cycle intermediates and responded to insulin and glucagon appropriately. In contrast, no glucose or glutamine consumption was detected in primary human hepatocytes over 4 h of exposure to high media concentrations of C-glucose or C-glutamine even in the presence of insulin. Nonetheless, cultured human hepatocytes were metabolically active and viable, as demonstrated by incorporation of media C-octanoic acid into Krebs cycle intermediates and ketone bodies. The failure to utilize glucose was not due to inhibition of glucokinase (hexokinase IV) since the human hepatocytes could readily incorporate C-glucose into glucuronic acid, as demonstrated by the production of C-glucuronide conjugates after addition of acetaminophen to the media. These novel observations support inhibition of phosphofructokinase-1, the other regulatory enzyme in glycolysis. Parts of this phenotype could be reproduced in the rat hepatocytes by replacing insulin with glucagon to the media. We conclude that under standard culture conditions human hepatocytes are in an extreme starved state. We believe this may result from prolonged fasting in the human liver donors combined with exposure to stress hormones such as, epinephrine, glucagon, and cortisol. Efforts should now be exerted to find culture conditions that will reverse this state to achieve more metabolically relevant cultures of human hepatocytes. [ABSTRACT FROM AUTHOR]

To investigate the metabolic changes that precede visible organogenesis in tissue culture, tobacco leaf explants were cultured on media supplemented with various plant growth regulators (PGRs) and analyzed with proton nuclear magnetic resonance (H NMR) spectroscopy. Principal component analysis (PCA) of H NMR spectral data was unable to differentiate between leaf explants cultured with α-naphthaleneacetic acid and those cultured with 6-benzyladenine after 4 days of culture; however, a difference was evident after 8 days of culture. A hierarchical dendrogram from PCA analysis could be grouping leaf explants cultured with various auxins separately from those treated by various cytokinins. However, leaf explants cultured with thidiazuron (TDZ) were identified as an outlier group; TDZ appeared to produce pleiotropic metabolic effects that differed from those induced by other PGRs. These results show that dedifferentiation can be initiated by either auxins or cytokinins, which is reflected by similar metabolic changes produced by the two distinct PGRs during the initial incubation period. The subsequent redifferentiation differs according to the PGR treatment, which is reflected by differential metabolic changes, depending on the fate of cells in organogenesis. Glutamine and glutamate levels increased approximately twofold in cytokinin-treated leaf explants compared with auxin-treated explants; however, changes in the levels of sugar compounds did not differ between the two treatments, demonstrating auxin regulation of the carbon/nitrogen ratio in favor of rooting. Taken together, our results suggest that H-NMR spectroscopy combined with multivariate analysis is a promising means for the metabolic evaluation of plant growth and differentiation. [ABSTRACT FROM AUTHOR]

Radiation accidents are rare events that induce radiation syndrome, a complex pathology which is difficult to treat. In medical management of radiation victims, life threatening damage to different physiological systems should be taken into consideration. The present study was proposed to identify metabolic and physiological perturbations in biofluids of mice during different phases of radiation sickness using H nuclear magnetic resonance (H NMR) spectroscopy and pattern recognition (PR) technique. The H NMR spectra of the biofluids collected from mice irradiated with 5 Gray (Gy) at different time points during radiation sickness were analysed visually and by principal components analysis. Urine and serum spectral profile clearly showed altered metabolic profiles during different phases of radiation sickness. Increased concentration of urine metabolites viz. citrate, α ketoglutarate, succinate, hippurate, and trimethylamine during prodromal and clinical manifestation phase of radiation sickness shows altered gut microflora and energy metabolism. On the other hand, serum nuclear magnetic resonance (NMR) spectra reflected changes associated with lipid, energy and membrane metabolism during radiation sickness. The metabonomic time trajectory based on PR analysis of H NMR spectra of urine illustrates clear separation of irradiated mice group at different time points from pre dose. The difference in NMR spectral profiles depicts the pathophysiological changes and metabolic disturbances observed during different phases of radiation sickness, that in turn, demonstrate involvement of multiple organ dysfunction. This could further be useful in development of multiparametric approach for better evaluation of radiation damage as well as for medical management during radiation sickness. [ABSTRACT FROM AUTHOR]

Object: The impact of inflammation in utero on amniotic fluid composition, the delivery term and the number of newborn rats per litter was investigated. The growth of newborns during the first fourteen days of life was analysed. Materials and methods: Changes in the metabolome were evaluated using H NMR spectroscopy combined with multivariate analysis. NMR spectra were segmented and principal component analysis was performed. Three groups were compared: a control group that received saline solution, a hyperthermic group (HYP) and a group that received injections of lipopolysaccharides (LPS) (350 μg/kg/day). Results: The most discriminating metabolites in the three profiles were identified, highlighting different metabolic pathways for providing glucose and energy to the foetus. The LPS group was characterized by glycolysis under anaerobic conditions, while the HYP group was characterized by a gluconeogenic amino acid pathway. These metabolic changes in amniotic fluid were accompanied by changes in the gestation outcome, the main differences concerning the mean number of pups per litter (control 9.74 ± 0.6, HYP 6.81 ± 0. and LPS 4.85 ± 1.11) and the biometric growth of the pups. Conclusion: Some consistent metabolic changes, observable by H NMR spectroscopy, occurred in amniotic fluid during prenatal stress caused by hyperthermia and LPS-induced inflammation and had an impact on the gestation outcome. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a malignant tumor with the worst prognosis among all cancers. At the time of diagnosis, surgical cure is no longer a feasible option for most patients, thus early detection of pancreatic cancer is crucial for its treatment. Metabolomics is a powerful new analytical approach to detect the metabolome of cells, tissue, or biofluids. Here, we report the application of H nuclear magnetic resonance (NMR) combined with principal components analysis to discriminate pancreatic cancer patients from healthy controls based on metabolomic profiling of the serum. The metabolic analysis revealed significant lower of 3-hydroxybutyrate, 3-hydroxyisovalerate, lactate, and trimethylamine- N-oxide as well as significant higher level of isoleucine, triglyceride, leucine, and creatinine in the serum from pancreatic cancer patients compared to that of healthy controls. Our data demonstrate that the subtle differences in metabolite profiles in serum of pancreatic cancer patients and that of healthy subjects as a result of physiological and pathological variations could be identified by NMR-based metabolomics and exploited as metabolic markers for the early detection of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Reactions of 2-acetamido-3,4,6-tri- O-acetyl-2-deoxy-α- D-glucopyranosyl chloride with thiosubstituted 5-thio-4-phenyl-Δ-l,2,4-triazolin-3-ones were studied in solid alkali-organic solvent and aqueous alkali-organic solvent catalytic phase transfer systems. The major products of glucosaminylation were the appropriate N-β-glucosaminides. The effects of reaction conditions on the product yield and composition were studied with the reaction α- D-glucosaminyl chloride with 5-methylthio-4-phenyl-Δ-l,2,4-triazolin-3-one. Optimal conditions of interphase glycosylation were found. The formation of N-l,2- trans-glycosidic bond was proved by H NMR and IR data as well as by comparison with the published spectral data for glycosides of similar structures. [ABSTRACT FROM AUTHOR]

The transformations of bis[ N-(3,5-di- tert-butylsalicylidene)-2,3,5,6-tetrafluoroanilinato]-titanium( iv) dichloride (LTiCl) occurring in toluene under the action of methylalumoxane (MAO) were studied by H NMR spectroscopy. The commercially available MAO containing trimethylaluminum (AlMe) and MAO free of AlMe (the so called 'dry' MAO) were used. The catalytic transformations of hex-1-ene involving the systems LTiCl-MAO were studied. We proposed the structures of the cationic titanium complexes formed in the absence and in the presence of hex-1-ene under the action of MAO. In the absence of olefin, neutral and cationic titanium complexes are decomposed under the action of AlMe according to the exchange reaction of the complex ligand with the methyl groups of AlMe to form LAlMe. The neutral complexes react considerably faster than the cationic ones. In the presence of olefin, decomposition of complexes under the action of AlMe is suppressed. The titanium complex activated by 'dry' MAO isomerizes hex-1-ene to hex-2-ene. In the presence of large amounts of TMA (commercial MAO), this reaction does not take place. [ABSTRACT FROM AUTHOR]

The hydrolysis of the iron nitrosyl complex {Fe[S(CH)NH](NO)}SO·2.5HO (CysAm) in water is not accompanied by the formation of its monomer form and is a reversible process. According to the ESR, H NMR, and spectrophotometric data, the dissolution of CysAm in DMSO affords the monomer form of CysAm. The kinetic parameters of the hydrolysis of CysAm in the dimer and monomer forms were determined by kinetic modeling. [ABSTRACT FROM AUTHOR]

A number of ( Z)- N,N-dialkyl- and ( Z)- N-acyl- N-alkyl- O-methylnicotinamide oximes was synthesized. Their configuration was confirmed by the NOESY experiment. Evaluation of fungicidal activity of compounds obtained was performed. [ABSTRACT FROM AUTHOR]