Influence of Polar Protic Solvents on Urea Morphology: A Combination of Experimental and Molecular Modeling

Abstract

The modification of crystal shapes is used intensively in designing particles with desired properties to ensure the efficiency of the manufacturing processes. In this work, urea crystals grew in various polar protic solvents by cooling crystallization that produced α-form urea. The aspect ratios of the crystals were found to be in the range from 14.77 to 1.44, grown in the following solvents: water > methanol > ethanol > isopentanol > isobutanol > pentanol > butanol > propanol > isopropanol. An attempt to establish a correlation between the nonbonded energy, solvent molecule size, binding energy, and the change in morphology revealed that the aforementioned factors could not accurately predict the aspect ratios of the urea crystals. The solvent-surface binding energy showed the {111} and {001} capping facets recorded the highest strength (most negative energy), while the {110} facet was the lowest. The inhibition of the solvent molecules on the {001} and polar {111} facets stopped the growth along the c-axis by stopping the formation of synthon A and synthon B, while the growth along the a-axis was halted by stopping the formation of synthon B. The transformation from elongated cuboid to prismoidal shape of urea was governed by the {111}/{110} energy ratio, i.e., it must be <1.78.

Crystal growth and morphology control of needle-shaped organic crystals

“…10). 82,83 The polar (1 1 1) and (−1 −1 −1) faces are not equivalent and the two end caps of needles grown from methanol are twisted by 90 degrees. The reason for this is that the growth rate of steps on [1 1 0] in the + c direction is twice that in the − c direction, while it is the reverse for [1 −1 0] and [−1 1 0].…”

Assessment of intermolecular interaction of mefenamic acid (Form II) in acetone and dimethylformamide (DMF) solution using molecular modelling technique

“…For example, the effect of solvents that contains hydroxyl functional groups on paracetamol Form I crystal surfaces carried out using this technique has shown that the most favourable solvent binding on the {002} facet delayed the growth of an elongated hexagonal morphology along the c-axis, forming a prism-like morphology (Shahrir et al, 2022). In their other work, they reported the influence of polar protic solvents on urea crystal morphology, which resulted in {111} and {001} capping facets as the most negative binding energy and {110} as the lowest negative binding energy, hence affecting the overall crystal morphology from an elongated cuboid to a prismoidal shape (Shahrir et al, 2023).…”

“…Among the factors affecting the polymorphism of mefenamic acid are the choice of solvent, temperature, supersaturation, stirring, and the presence of interfaces or impurities during the crystallisation process (Abdul Mudalip et al, 2018). This work aims to investigate the nature of the solute-solvent interactions between mefenamic acid (Form II) and acetone or dimethylformamide (DMF) at the molecular level using the surface docking method as described by previous researchers (Shahrir et al, 2022;Shahrir et al, 2023). The method involves the docking of the solvent molecule on top of the crystal surfaces of interest, e.g., {001}, {010}, and {011} facets.…”

Uncovering the Influence Mechanism of Solvent on Crystal Morphology via a Combined Experimental and Theoretical Method: The Case of Aceclofenac

“…It plays a pivotal role in assessing product quality . The crystal habit is predominantly influenced by the molecular arrangement within the crystals and the external environment, , such as the solvent, , supersaturation, , temperature, template, and additives . The crystals’ habit significantly impacts the overall quality of the final product during industrial crystallization.…”