Machine Learning Accelerates Crystallization for Structure Determination

C Cui‐Zhou Luan (State Key Laboratory of Bioactive Molecules and Druggability Assessment College of Chemistry and Materials Science Guangdong Provincial Key Laboratory of Supramolecular Coordination Chemistry Jinan University Guangzhou P. R. China) X Xue‐Zhi Wang (State Key Laboratory of Bioactive Molecules and Druggability Assessment College of Chemistry and Materials Science Guangdong Provincial Key Laboratory of Supramolecular Coordination Chemistry Jinan University Guangzhou P. R. China) J Jian‐Guo Song (State Key Laboratory of Bioactive Molecules and Druggability Assessment College of Chemistry and Materials Science Guangdong Provincial Key Laboratory of Supramolecular Coordination Chemistry Jinan University Guangzhou P. R. China) Y Yu Gu J Jing Wu Y Ye‐Ting Wang (State Key Laboratory of Bioactive Molecules and Druggability Assessment College of Chemistry and Materials Science Guangdong Provincial Key Laboratory of Supramolecular Coordination Chemistry Jinan University Guangzhou P. R. China) J Jin‐Feng Liang (State Key Laboratory of Bioactive Molecules and Druggability Assessment College of Chemistry and Materials Science Guangdong Provincial Key Laboratory of Supramolecular Coordination Chemistry Jinan University Guangzhou P. R. China) J Jia‐Le Rao (State Key Laboratory of Bioactive Molecules and Druggability Assessment College of Chemistry and Materials Science Guangdong Provincial Key Laboratory of Supramolecular Coordination Chemistry Jinan University Guangzhou P. R. China) M Mo Xie (State Key Laboratory for Flexible Electronics (LoFE)) J Jonathan R. Nitschke (Yusuf Hamied Department of Chemistry) D Dan Li

Abstract

ABSTRACT Single‐crystal X‐ray diffraction (SCXRD) is a powerful tool for structural elucidation, but requires high‐quality crystals that are often difficult to obtain. The crystalline mate strategy helps overcome this limitation by facilitating the co‐crystallization of volatile or complex molecules, with few restrictions on size or purity. However, defining its scope of applicability remains challenging, until now requiring experimental trial‐and‐error screening. Here, we demonstrate a machine learning (ML)‐accelerated workflow that rapidly identifies suitable candidates for co‐crystallization. Through feature engineering and workflow optimization, we trained the MCC model, achieving over 95% prediction accuracy. Experimental validation confirmed 114 successful co‐crystals among 120 predicted compounds. The wide structural and functional diversity exhibited highlights the robustness and broad applicability of our strategy, enabling efficient discovery of new structures by SCXRD under standard laboratory conditions.

Article Details

Volume / Issue Vol. 65, Issue 25
Published June 15, 2026
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (11)

C

Cui‐Zhou Luan

State Key Laboratory of Bioactive Molecules and Druggability Assessment College of Chemistry and Materials Science Guangdong Provincial Key Laboratory of Supramolecular Coordination Chemistry Jinan University Guangzhou P. R. China

X

Xue‐Zhi Wang

State Key Laboratory of Bioactive Molecules and Druggability Assessment College of Chemistry and Materials Science Guangdong Provincial Key Laboratory of Supramolecular Coordination Chemistry Jinan University Guangzhou P. R. China

J

Jian‐Guo Song

State Key Laboratory of Bioactive Molecules and Druggability Assessment College of Chemistry and Materials Science Guangdong Provincial Key Laboratory of Supramolecular Coordination Chemistry Jinan University Guangzhou P. R. China

Y

Yu Gu

J

Jing Wu

Y

Ye‐Ting Wang

State Key Laboratory of Bioactive Molecules and Druggability Assessment College of Chemistry and Materials Science Guangdong Provincial Key Laboratory of Supramolecular Coordination Chemistry Jinan University Guangzhou P. R. China

J

Jin‐Feng Liang

State Key Laboratory of Bioactive Molecules and Druggability Assessment College of Chemistry and Materials Science Guangdong Provincial Key Laboratory of Supramolecular Coordination Chemistry Jinan University Guangzhou P. R. China

J

Jia‐Le Rao

State Key Laboratory of Bioactive Molecules and Druggability Assessment College of Chemistry and Materials Science Guangdong Provincial Key Laboratory of Supramolecular Coordination Chemistry Jinan University Guangzhou P. R. China

M

Mo Xie

State Key Laboratory for Flexible Electronics (LoFE)

J

Jonathan R. Nitschke

Yusuf Hamied Department of Chemistry

D

Dan Li