title: Two-dimensional proton-detected (35)Cl/(1)H correlation solid-state NMR experiment under fast magic angle sample spinning: application to pharmaceutical compounds.
abstract: The determination of structure of hydrochloride salts of active pharmaceutical ingredients (HCl APIs) utilizing (35)Cl solid-state NMR studies has been of considerable interest in the recent past. Until now these studies relied on the (35)Cl 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 (35)Cl. In this contribution we demonstrate the two-dimensional (2D) (35)Cl/(1)H correlation measurement by using the proton detection-based (indirect observation of (35)Cl via(1)H) 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 (35)Cl-(1)H heteronuclear dipolar interactions. The applicability of (35)Cl indirect detection method is first demonstrated on hydrochloride salts of amino acids, l-tyrosine·HCl and l-histidine·HCl·H2O following which the 2D (35)Cl/(1)H 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 (35)Cl/(1)H correlations provide the precise determination of (1)H chemical shifts of nearby (35)Cl nuclei.
authors: RIKEN CLST-JEOL Collaboration Center, RIKEN, Yokohama, Kanagawa 230-0045, Japan. yunishiy@jeol.co.jp.
authors: Manoj Kumar
authors: MK
authors: Pandey
authors: JEOL RESONANCE Inc., Musashino, Akishima, Tokyo 196-8558, Japan.
authors: Hiroshi
authors: H
authors: Kato
authors: JEOL RESONANCE Inc., Musashino, Akishima, Tokyo 196-8558, Japan.
authors: Yuji
authors: Y
authors: Ishii
authors: RIKEN CLST-JEOL Collaboration Center, RIKEN, Yokohama, Kanagawa 230-0045, Japan. yunishiy@jeol.co.jp and JEOL RESONANCE Inc., Musashino, Akishima, Tokyo 196-8558, Japan.
authors: Yusuke
authors: Y
authors: Nishiyama
mesh_terms: D002626:Chemistry, Pharmaceutical; D002713:Chlorine / Q000737:chemistry; D006851:Hydrochloric Acid / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011522:Protons; D014443:Tyrosine / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D011522:Protons; D014443:Tyrosine; D002713:Chlorine; D006851:Hydrochloric Acid