Low-Temperature Polymorphic Transformation of β-Lactam Antibiotics

Luo Luo,Li Li,He He,Liu Liu

doi:10.3390/cryst9090460

Abstract

Abstract: Polymorphic screening and transformation of molecular crystals are presently popular research areas in pharmaceutical studies. In this study, we developed an ab initio method to examine the structures, spectra, and stabilities of β-lactam (trans-13-azabicyclo[10.2.0]tetradecan-14-one), an important component of antibiotics. Based on the density functional theory (DFT) and second-order Møller-Plesset perturbation (MP2) methods, the present work demonstrated that forms I and II have isomorphic structures but can be distinguished by their Gibbs free energies and vibrational spectra. Forms I and II show a low-temperature polymorphic transformation at 308 K, where form I is stable below 308 K and form II is stable above 308 K. The proposed method suggests that the theoretical calculation can be used as a tool to effectively distinguish the isomorphic structures, and temperature-induced polymorphic transformation has far-reaching significance for drug storage and design.

Highlights

With the continuous improvement of drug design technology, research on the crystal structure of pharmaceutical molecules has become increasingly important. [1,2,3]
Modern industrial manufacturers place great importance on drug storage and transportation to avoid the structural changes and polymorphic transformations caused by external environments, using tailored operating conditions
crystal structure prediction (CSP) is generally used for screening crystal structures and predicting the most stable structure, and there have been many important discoveries in the fields of computational materials discovery, drug design, high-pressure chemistry, and mineralogy of the earth’s and planetary interiors

Summary

Introduction

With the continuous improvement of drug design technology, research on the crystal structure of pharmaceutical molecules has become increasingly important. [1,2,3]. With the continuous improvement of drug design technology, research on the crystal structure of pharmaceutical molecules has become increasingly important. CSP provides greater potential for rational crystal design, but it is difficult to distinguish polymorphic structures according to their tiny differences in energy and spatial distribution. In this context, an advanced model that can distinguish polymorphs and predict their temperature-induced polymorphic transformation could eliminate this barrier to entry and promote widespread adoption to advance drug storage technology into the generation [8,9]

Methods

Results

Conclusion