The Solid-Phase Transition of Carbapenem CS-023 Polymorphs and the Change in Helicity Observed in the Transition

Author:

Matsuura Shinji1,Igarashi Koichi1,Azuma Masayuki1,Ooshima Hiroshi2

Affiliation:

1. Department of Applied Chemistry and Bioengineering, Graduate School of Engineering, Osaka City University, Osaka 558-8585, Japan

2. Kansai Chemical Engineering Co., Ltd., Amagasaki 661-0024, Japan

Abstract

Anti-solvent crystallization of carbapenem CS-023 was performed at 25 °C. The following results were obtained: (1) A solvate crystal, Form A (5/2 Ethanol·1/2 H2O), was recovered from 80 v/v% ethanol solution; (2) Form A transformed to Form H (4H2O) through solid-phase transition through the solvate-free polymorph, Form A-2, and Form A also transformed into Form C (1Ethanol·3H2O) through solvent-mediated transformation. In the present study, we found that Form C also transforms to Form H through the solid-phase transition through the solvate-free polymorph Form C-2. The three polymorphs, Forms A, H, and C, were composed of helical chain structures. However, there was an incomprehensible affair in the solid-phase transition among the three polymorphs. Namely, Form A comprised a left-handed helix. On the other hand, Form C’s and Form H’s helix chains were in a left- and right-handed helix complex, respectively. The solid-phase transition of Form A into Form H suggested a switch in helicity in the solid. We attempted to explain the helicity change in the solid-phase transition. As a result, we suggest that the over-absorption of water by Form A-2 at high humidity plays a vital role in the helicity change.

Publisher

MDPI AG

Reference22 articles.

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