Purpose. To determine the crystal structure of the neotame anhydrate polymorph G and to evaluate X-ray powder diffractometry (XRPD) with molecular modeling as an alternative method for determining the crystal structure of this conformationally flexible dipeptide. Methods. The crystal structure of polymorph G was determined by single crystal X-ray crystallography (SCXRD) and also from the X-ray powder diffraction (XRPD) pattern using molecular modeling (Cerius2, ™, Powder Solve module). Results. From SCXRD, polymorph G crystals are orthorhombic with space group of P212121 with Z = 4, unit cell constants: a = 5.5999(4), b = 11.8921(8), c = 30.917(2) Å, and one neotame molecule per asymmetric unit. The XRPD pattern of polymorph G, analyzed by Cerius2, ™ software, led to the same P212121 space group and almost identical unit cell dimensions. However, with 13 rigid bodies defined, Cerius2, ™ gives a conformation of the neotame molecule, which is different from that determined by SCXRD. Conclusions. For neotame anhydrate polymorph G, the unit cell dimensions calculated from XRPD were almost identical to those determined by SCXRD. However, the crystal structure determined by XRPD closely resembled that determined by SCXRD, only when the correct conformation of the neotame molecule had been chosen before detailed analysis of the XRPD pattern.
Bibliographical noteFunding Information:
We thank The NutraSweet Company for financial support and the United States Pharmacopeial (USP) Convention for the award of a USP Fellowship in Drug Standards Research to Zedong Dong. We also thank Novartis Corporation for a Graduate Research Fellowship and Pharmacia Corporation for a Walter F. Enz award to Zedong Dong.
Copyright 2017 Elsevier B.V., All rights reserved.
- Crystal structure
- Molecular modeling
- X-ray crystallography
- X-ray powder diffractometry