文献类型：期刊文献

英文题名：Nucleation Behavior of Tiamulin Hydrogen Fumarate: Insights from Metastable Zone Widths, Nucleation Theory, and Molecular Simulation

作者：Chen, Qidan[1];Zhang, Qi[1];Li, Qiang[1];Zhou, Xiaojie[1];Yan, Yizhen[2];Zhang, Xiangyang[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Chem Engn, Shanghai 200237, Peoples R China;[2]Univ Sussex, Sch Engn & Informat, Dept Engn & Design, Brighton BN1 9RH, England

年份：2025

卷号：25

期号：21

起止页码：8956

外文期刊名：CRYSTAL GROWTH & DESIGN

收录：;EI(收录号：20254519451395);WOS:【SCI-EXPANDED(收录号:WOS:001599902100001)】；

基金：This work was financially supported by the Natural Science Foundation of Shanghai Municipality (No. 23ZR1417100).

语种：英文

外文关键词：Complexation - Free energy - Gibbs free energy - Hydrogen - Hydrogen bonds - Interfacial energy - Nucleation - Solvents

摘要：The systematic investigation of nucleation is critical for controlling and optimizing the crystallization process. The metastable zone width (MSZW) of tiamulin hydrogen fumarate (THF) was determined across a range of temperatures in four different solvents during this study. A self-consistent Nyvlt-like approach along with modified Sangwal's model and classical nucleation theory collectively reveal synchronized solvent-dependent variations in critical nucleation parameters, including interfacial energy, critical Gibbs free energy, and critical nucleation size. These results indicate that the ease of THF nucleation in the four ester solvents increases in the order isobutyl acetate < butyl acetate < isopropyl acetate < ethyl acetate. The interfacial energy shows a decreasing trend with increasing saturation temperature, which explains the enhanced nucleation tendency at higher temperatures. Finally, molecular electrostatic potential surface, Hirshfeld surface, and radial distribution function based on molecular dynamics simulation were performed to show the influence of hydrogen bonds between THF and solvents on the nucleation behavior. The relative hydrogen bond strength positively correlates with the extent of the MSZW in the four solvent systems, revealing that the hydrogen bonding interaction is a critical molecular-level factor to govern both the MSZW characteristics and nucleation behavior of THF in different solvent environments.