Solid-state stereochemistry of (-)-scopolamine hydrobromide sesquihydrate, a new polymorph of the anticholinergic drug.
The solid-state structure of (-)-scopolamine hydrobromide sesquihydrate was determined by single-crystal X-ray diffraction analysis at low temperature. (Nr,C alpha-S)-(-)-Scopolamine hydrobromide sesquihydrate gives crystals belonging to the tetragonal space group P4(3)2(1)2, and at 180 K: a = 11.870(4), c = 26.193(3) A, V = 3691(1) A3, Z = 8, R(F) = 0.062, and Rw(F) = 0.059. Thermogravimetric analysis afforded a total weight loss of approximately 6%, consistent with a loss of 1.5 molecules of water and in accord with the sesquihydrate stoichiometry found by single-crystal X-ray crystallography. The unit cell dimensions, molecular structure, basic packing arrangement [minus the full water molecule], and the crystal system are all the same as that of the P4(1)2(1)2 hemihydrate form [R(F) = 0.09] reported earlier by Pauling and Petcher. This suggests that the previously reported "hemihydrate" description of the structure should be reconsidered. In addition to partial dehydration of the sesquihydrate crystal, non-observance of the eight water molecules might have arisen from their relatively large thermal motions at ambient temperature coupled with a lack of sufficient data versus the number of variable parameters. The phenyl ring syn-to-oxirane arrangement in the sesquihydrate form is the same as that in the corresponding crystalline methyliodide quaternary ammonium salt and in (-)-(Ns,C alpha-S)-hyoscyamine [atropine] hydrobromide, but differs from the elongated anti-to-oxirane arrangement in anhydrous (Nr,C alpha-S)-(-)-scopolamine hydrobromide.(ABSTRACT TRUNCATED AT 250 WORDS)
Michel
A
A
Département de Chimie, Université de Sherbrooke, Québec, Canada.
Drouin
M
M
Glaser
R
R
D018360:Crystallography, X-Ray; D006859:Hydrogen / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D012601:Scopolamine / Q000737:chemistry*; D013237:Stereoisomerism; D013818:Thermogravimetry
D006859:Hydrogen; D012601:Scopolamine