Toward Understandingthe Crystal Growth of 7‑AminocephalosporanicAcid Based on the Growth Unit

Crystal growth is a key stage during the crystallization process that influences the properties of the crystal and the downstream processing, while the growth unit forms and behaviors during crystal growth have not been thoroughly understood. In this work, growth unit forms and behaviors of 7-aminocephalosporanic acid (7-ACA) during the crystal growth process, including the bulk diffusion and surface integration stages in aqueous solution, were systematically explored through experiment and molecular dynamics simulation. First, the self-association of the 7-ACA molecule into the dimer in the aqueous solution was confirmed by ultraviolet and Fourier transform infrared spectroscopies. Moreover, the exact dimer structure was mainly determined as N₇H₈···O₄C₂₂ (1.966 Å/154°, AGG I) and N₇H₉···O₃–C₂₂ (1.477 Å/153°, AGG II) hydrogen-bonded dimers based on the MD simulation and nuclear Overhauser effect spectroscopy, acting as the growth unit in the solution. Furthermore, dependent on the mean square displacement, diffusion coefficient, surface chemistry, and interaction energy results, it was revealed that the AGG II growth unit was easier to diffuse from the bulk solution and adsorbed onto the crystal surface to promote crystal growth in comparison with AGG I. In addition, the diffusion and attachment of the growth units onto the (0 0 1) face were the most difficult, which led to the slowest growth rate and most dominant morphological face.