title: Probing intermolecular hydrogen bonding in sibenadet hydrochloride polymorphs by high-resolution (1) H double-quantum solid-state NMR spectroscopy.
abstract: Molecular packing in two polymorphs of sibenadet hydrochloride (AR-C68397AA, Viozan™) is investigated using a combined experimental (1) H double-quantum (DQ) solid-state magic-angle spinning nuclear magnetic resonance and computational (gauge including projected augmented wave calculation of chemical shifts) approach. For Form I, NH-NH and NH-OH (1) H DQ peaks are observed corresponding to nearest distances of 2.62 and 2.87 Å, respectively, for the intermolecular hydrogen-bonding arrangement in the single-crystal X-ray diffraction structure. The same (1) H DQ peaks at the same (1) H chemical shifts are observed for Form II, for which there is no single-crystal diffraction structure, indicating the same intermolecular hydrogen-bonding arrangement of the benzothiazolone moieties as in Form I. (1) H DQ build-up (as a function of the DQ recoupling time) curves are presented for the resolved NH-NH and NH-OH DQ peaks for the two polymorphs. For Form I, the ratio of the maximum intensity for the NH-OH and NH-NH DQ peaks is in excellent agreement with the ratio of the summed squares of the H-H dipolar couplings, as determined using H-H distances from the crystal structure up to 4 Å. Small differences in the (1) H DQ build-up behaviour for the two polymorphs are attributed to differences in the longer-range NH-OH distances associated with different inter-layer arrangements.
authors.affiliation: Department of Physics, University of Warwick, Coventry CV4 7AL, United Kingdom.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Bradley
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Pickard
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Burley
authors.forename: Dave R
authors.initials: DR
authors.lastname: Martin
authors.forename: Leslie P
authors.initials: LP
authors.lastname: Hughes
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Cosgrove
authors.forename: Steven P
authors.initials: SP
authors.lastname: Brown
mesh_terms: D000318:Adrenergic beta-Agonists / Q000737:chemistry*; D018360:Crystallography, X-Ray; D018491:Dopamine Agonists / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D011522:Protons; D011789:Quantum Theory; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D000318:Adrenergic beta-Agonists; D018491:Dopamine Agonists; D011522:Protons; D013844:Thiazoles; C116267:sibenadet