Blog
About

7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Two-dimensional proton-detected 35Cl/1H correlation solid-state NMR experiment under fast magic angle sample spinning: application to pharmaceutical compounds

      Read this article at

      ScienceOpenPublisher
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          In this study, we have measured 35Cl/ 1H correlations in hydrochloride salts of active pharmaceutical ingredients (HCl APIs) using the D-HMQC pulse sequence at fast MAS.

          Abstract

          The determination of structure of hydrochloride salts of active pharmaceutical ingredients (HCl APIs) utilizing 35Cl solid-state NMR studies has been of considerable interest in the recent past. Until now these studies relied on the 35Cl direct observation method which has its own limitations in terms of the sensitivity and resolution due to the quadrupolar nature and the low gyromagnetic ratio of 35Cl. In this contribution we demonstrate the two-dimensional (2D) 35Cl/ 1H correlation measurement by using the proton detection-based (indirect observation of 35Cl via 1H) approach under fast magic angle sample spinning (MAS: 70 kHz). The main advantages of this approach over the direct observation method are highlighted in the present study. We have employed heteronuclear magnetization transfer through the recoupling of 35Cl– 1H heteronuclear dipolar interactions. The applicability of 35Cl indirect detection method is first demonstrated on hydrochloride salts of amino acids, l-tyrosine·HCl and l-histidine·HCl·H 2O following which the 2D 35Cl/ 1H correlations are obtained for HCl APIs, procainamide HCl (Proc) and aminoguanidine HCl (Amin). On the basis of separation between the central transition (CT) and satellite transition (ST) peaks, and the shape/width of CT powder patterns, it is also shown that the quadrupolar parameters which are useful for the elucidation of the molecular structure can be determined. Moreover, the 35Cl/ 1H correlations provide the precise determination of 1H chemical shifts of nearby 35Cl nuclei.

          Related collections

          Most cited references 29

          • Record: found
          • Abstract: not found
          • Article: not found

          Multiple-Quantum Magic-Angle Spinning NMR: A New Method for the Study of Quadrupolar Nuclei in Solids

            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            High resolution solid-state N.M.R.

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              De novo 3D structure determination from sub-milligram protein samples by solid-state 100 kHz MAS NMR spectroscopy.

              Solid-state NMR spectroscopy is an emerging tool for structural studies of crystalline, membrane-associated, sedimented, and fibrillar proteins. A major limitation for many studies is still the large amount of sample needed for the experiments, typically several isotopically labeled samples of 10-20 mg each. Here we show that a new NMR probe, pushing magic-angle sample rotation to frequencies around 100 kHz, makes it possible to narrow the proton resonance lines sufficiently to provide the necessary sensitivity and spectral resolution for efficient and sensitive proton detection. Using restraints from such spectra, a well-defined de novo structure of the model protein ubiquitin was obtained from two samples of roughly 500 μg protein each. This proof of principle opens new avenues for structural studies of proteins available in microgram, or tens of nanomoles, quantities that are, for example, typically achieved for eukaryotic membrane proteins by in-cell or cell-free expression.
                Bookmark

                Author and article information

                Affiliations
                [1 ]RIKEN CLST-JEOL Collaboration Center
                [2 ]RIKEN
                [3 ]Yokohama
                [4 ]Japan
                [5 ]JEOL RESONANCE Inc.
                [6 ]Akishima
                Journal
                PPCPFQ
                Physical Chemistry Chemical Physics
                Phys. Chem. Chem. Phys.
                Royal Society of Chemistry (RSC)
                1463-9076
                1463-9084
                2016
                2016
                : 18
                : 8
                : 6209-6216
                10.1039/C5CP06042G
                © 2016
                Product
                Self URI (article page): http://xlink.rsc.org/?DOI=C5CP06042G

                Comments

                Comment on this article