Molecular recognition and crystallization behavior of Lisinopril ester

Abstract

The influence of the solvent on the crystallization of N²-((S)-1-ethoxycarbonyl-3-phenylpropyl) -N⁶-trifluoroacetyl-L-lysyl-L-proline (Lisinopril ester) was investigated. It was found that Lisinopril ester could be crystallized from about 20 kinds of solvent, all of which had some similarities in molecular structure. The amount of the solvent inside the obtained crystals was approximately 1 to 100 mol% per Lisinopril ester and it was influenced by the molecular form or the bulkiness of the solvent molecule and the kind of substituents present therein. It was recognized that the presence of a suitable substituent in the solvent molecule is essential for crystallization and that there was a possibility that the substituent in the solvent molecule interacts with, at a minimum, the trifluoroacetylamino group in a Lisinopril ester molecule. It is suggested that the above crystallization of Lisinopril ester is a kind of adductive crystallization wherein the host is Lisinopril ester and the guest is the crystallizing solvent itself.