Diffusion-Ordered NMR Spectroscopy Application for Analysis of Polysaccharides

Diffusion-ordered nuclear magnetic resonance spectroscopy (DOSY) is a molecular transport method in analytical chemistry, based on experimental recording of the molecules’ translational mobility at thermodinamic equilibrium in a solution. The translational mobility is characterised quantitatively by a self-diffusion coefficient. The aim of the study was to summarise the main trends in application of DOSY for the analysis of natural and modified natural polysaccharides used in pharmaceuticals and pharmaceutical biotechnology. The review shows that this method is an effective instrument for monitoring fractionation during isolation of polysaccharides from a natural mixture, for estimating their average molecular weight and molecular weight distribution, and for studying the formation of supramolecular systems based on polysaccharides. The paper describes main issues of the precise measurement of polysaccharide macromolecules self-diffusion coefficients and provides the correction factors to compensate for errors caused by fluctuations in temperature and viscosity of solutions. The observed scatter of self-diffusion coefficients of narrowly dispersed polymer macromolecules nuclei is explained using the polyphase concept. The paper illustrates ways of describing translational mobility of a polyphase polymer macromolecule as a whole. The authors summarise values of the gradient pulse sequence parameters used in quantitative measurements of self-diffusion coefficients of linear, low-branched, and branched polysaccharides

NMR Spectroscopy Study of the Effect of the Molecular Mass of Hypromellose Phthalate on Its Solubility

Scientific relevance. Hypromellose phthalate is used in enteric coatings for oral medicinal products. The proportion of phthalate groups in the polymer is standardised because it has a significant effect on solubility. Whereas, the molecular mass of hypromellose phthalate is not controlled, and its impact on solubility in media with different pH values is understudied.Aim. The study aimed to employ NMR spectroscopy to investigate the effect the molecular mass of hypromellose phthalate may have on the dissolution kinetics at the pH value declared by the polymer manufacturer.Materials and methods. The study analysed hypromellose phthalate isolated from proton-pump inhibitor enteric coatings and the hypromellose phthalate reference standard. The molecular mass of the polymer was estimated by diffusion-ordered NMR spectroscopy (DOSY) with polyethylene glycols of known molecular masses for calibration. The authors studied the dissolution profiles of hypromellose phthalates of different molecular masses using 1H NMR spectra.Results. The authors developed a procedure for estimating the average molecular mass of hypromellose phthalate by DOSY. The procedure showed variations in the molecular mass of the polymer in the test samples; the molecular mass scatter amounted to 10 kDa. The dissolution profile of the test samples in an aqueous buffer solution (pH 5.59) was described by a linear function during the first hour. The slope characterising the dissolution rate varied from 10° to 36°.Conclusions. The variation in the molecular mass of hypromellose phthalate significantly affects the dissolution rate of the test samples. The function of the dissolution rate against the molecular mass of hypromellose phthalate is non-linear. The article provides a compelling reason for further research to derive a correlation equation for the dissolution rate of hypromellose phthalate as a function of two variables (molecular mass and proportion of phthalate groups in the polymer)

First results of the Kourovka Planet Search: discovery of transiting exoplanet candidates in the first three target fields

We present the first results of our search for transiting exoplanet candidates as part of the Kourovka Planet Search (KPS) project. The primary objective of the project is to search for new hot Jupiters which transit their host stars, mainly in the Galactic plane, in the $R_c$ magnitude range of 11 to 14 mag. Our observations were performed with the telescope of the MASTER robotic network, installed at the Kourovka astronomical observatory of the Ural Federal University (Russia), and the Rowe-Ackermann Schmidt Astrograph, installed at the private Acton Sky Portal Observatory (USA). As test observations, we observed three celestial fields of size $2\times2$ deg$^2$ during the period from 2012 to 2015. As a result, we discovered four transiting exoplanet candidates among the 39000 stars of the input catalogue. In this paper, we provide the description of the project and analyse additional photometric, spectral, and speckle interferometric observations of the discovered transiting exoplanet candidates. Three of the four transiting exoplanet candidates are most likely astrophysical false positives, while the nature of the fourth (most promising) candidate remains to be ascertained. Also, we propose an alternative observing strategy that could increase the project's exoplanet haul.Comment: 11 pages, 16 figures; Accepted for publication in Monthly Notices of the Royal Astronomical Society 201

NMR spectroscopy study of the structure of hypromellose phthalate, a component of enteric coatings of medicinal products

Scientific relevance. Hypromellose phthalate is a component of enteric coatings used to modify active substance release from oral medicinal products in the small intestine. The release rate directly depends on the non-stoichiometric composition of the polymer, first of all, on the proportion of phthalate groups in the macromolecule. It is therefore necessary to develop reliable analytical procedures for determining the structure of hypromellose phthalate to evaluate the dissolution rate of medicinal products containing the polymer.Aim. The study aimed to develop an analytical procedure for quantifying the proportion of phthalate groups in hypromellose phthalate samples using NMR spectroscopy and to determine the relationship between the polymer dissolution rate in aqueous buffer solutions and its structural features (degree of molar substitution and molecular mass).Materials and methods. The study examined hypromellose phthalate samples isolated from enteric coatings of proton-pump inhibitors and used the reference standard for hypromellose phthalate. The non-stoichiometric composition of the polymer was determined by 13C NMR spectroscopy.Results. The authors established the conditions required to separate hypromellose phthalate from the other coating components and identified the characteristic 13C NMR signals that may be used to differentiate between the structural fragments of hypromellose phthalate. The study demonstrated the relationship between the dissolution rate and the structure of the polymer. Commercial grades of hypromellose phthalate were shown to differ in composition and, as a result, in their dissolution kinetics (in particular, the threshold pH for the onset of dissolution (5.0–5.5), as well as the dissolution rates at the same pH).Conclusions. The authors developed NMR-based procedures to determine the proportion of phthalate groups on the basis of their mass fraction in a weighted hypromellose phthalate sample and the degree of molar substitution of the polymer. The results support the applicability of these analytical procedures to the characterisation of sample composition in polymer dissolution rate studies. In principle, it is possible to derive a multiple linear regression equation that describes the dissolution rate of hypromellose phthalate as a function of the molecular mass and the molar substitution with phthalate groups. Further investigation of a larger number of polymer samples with different compositions is needed to improve the regression model and demonstrate its statistical significance. In addition to the proportion of phthalate groups, the pharmacopoeial analysis of hypromellose phthalate should also control the molecular mass of the polymer

Constraints on new interactions from neutron scattering experiments

Constraints for the constants of hypothetical Yukawa-type corrections to the Newtonian gravitational potential are obtained from analysis of neutron scattering experiments. Restrictions are obtained for the interaction range between 10^{-12} and 10^{-7} cm, where Casimir force experiments and atomic force microscopy are not sensitive. Experimental limits are obtained also for non-electromagnetic inverse power law neutron-nucleus potential. Some possibilities are discussed to strengthen these constraints.Comment: 18 pages, 3 figure

Dark Matter Search Perspectives with GAMMA-400

GAMMA-400 is a future high-energy gamma-ray telescope, designed to measure the fluxes of gamma-rays and cosmic-ray electrons + positrons, which can be produced by annihilation or decay of dark matter particles, and to survey the celestial sphere in order to study point and extended sources of gamma-rays, measure energy spectra of Galactic and extragalactic diffuse gamma-ray emission, gamma-ray bursts, and gamma-ray emission from the Sun. GAMMA-400 covers the energy range from 100 MeV to ~3000 GeV. Its angular resolution is ~0.01 deg(Eg > 100 GeV), and the energy resolution ~1% (Eg > 10 GeV). GAMMA-400 is planned to be launched on the Russian space platform Navigator in 2019. The GAMMA-400 perspectives in the search for dark matter in various scenarios are presented in this paperComment: 4 pages, 4 figures, submitted to the Proceedings of the International Cosmic-Ray Conference 2013, Brazil, Rio de Janeir