Crystal structure of neotame anhydrate polymorph G

Area of Science:

• Crystallography
• Materials Science
• Computational Chemistry

Background:

• Neotame is a conformationally flexible dipeptide sweetener.
• Polymorphism in neotame anhydrate can affect its physical properties.
• Understanding crystal structures is vital for material characterization and development.

Purpose of the Study:

• To determine the crystal structure of neotame anhydrate polymorph G.
• To evaluate X-ray powder diffractometry (XRPD) combined with molecular modeling as an alternative to single crystal X-ray crystallography (SCXRD) for structural determination.
• To assess the impact of molecular conformation on XRPD-based crystal structure analysis.

Main Methods:

• Crystal structure determination of polymorph G using SCXRD.
• Crystal structure analysis of polymorph G from XRPD data utilizing molecular modeling software (Cerius2, Powder Solve module).
• Comparison of structural parameters and molecular conformations obtained from SCXRD and XRPD methods.

Main Results:

• SCXRD revealed polymorph G crystals are orthorhombic with space group P2(1)2(1)2(1) and specific unit cell dimensions.
• XRPD analysis using molecular modeling yielded the same space group and nearly identical unit cell dimensions.
• Molecular modeling with 13 rigid bodies resulted in a neotame conformation differing from the SCXRD findings.

Conclusions:

• XRPD with molecular modeling can provide accurate unit cell dimensions for neotame anhydrate polymorph G, comparable to SCXRD.
• The accuracy of the crystal structure determined by XRPD is highly dependent on selecting the correct molecular conformation prior to analysis.
• This study highlights the potential of XRPD and molecular modeling as a viable alternative for crystal structure determination, provided conformational flexibility is adequately addressed.