Multi-pathway supramolecular self-assembly of meropenem regulated by solvents

Understanding the self-assembly of organic small molecules is a long-standing objective in the fields of pharmaceutical crystallization, biomineralization, and materials science. However, the complexity of small-molecule self-assembly and the constraints imposed by relevant timescales makes related investigations particularly challenging. In this work, a multiscale approach was adopted to investigate the influence of different solvents on the supramolecular self-assembly of organic small molecules. It was found that two distinct mechanisms-formation of solvent-rich clusters and particle attachment-recognition-assembly-exist during the self-assembly process in different solvents. Subsequently, based on the particle recognition-assembly mechanism, the solvent environment was systematically varied to transform drug molecules from well-ordered assembled aggregates into disordered gel structures, which subsequently underwent self-repair to form crystals within the gel environment. Finally, molecular dynamics simulation results revealed that the formation of the disordered structure was attributed to miscoding at the molecular level under the influence of the solvent. The solvent responsiveness of the supramolecular self-assembly process provides a foundation for regulating the nucleation of small organic small molecules and for the bottom-up design of drug delivery materials.