Crystallisation of organic materials from the solution phase: a molecular, synthonic and crystallographic perspective

A short review of X-ray topographic studies of crystals grown from solution is presented. The dislocation configurations characteristic of such crystals are described, and Klapper's explanation in terms of minimization of the elastic energy of a dislocation per unit growth length is highlighted. It is shown that the principles apply to crystals grown not only from low temperature solution but also by hydrothermal growth and growth from fluxed melts. Recent studies of growth of protein crystals have found that they have similar dislocation configurations and characteristics to those of ionic and small organic molecule crystals grown from solution.

Section: Discussionmentioning

confidence: 99%

X-ray Diffraction Topography (Imaging) of Crystals Grown from Solution: A Short Review

Tanner

2023

“…Alpha urea structures are interlinked within their periodic space through an intermolecular hydrogen bonding network. The periodic hydrogen bonds are extended into all three dimensions of its periodic space (3D hydrogen bond dimensionality) Figure shows the crystal structure of urea packed in its lattice and viewed from the x -, y -, and z -directions.…”

Section: Methodsmentioning

confidence: 99%

“…These functional groups can therefore serve as hydrogen bond donors and acceptors to form hydrogen bonds with other polar solvent molecules in the solution. This nonbonded hydrogen bonding provides the strongest interaction energy compared to the van der Waals and electrostatic interactions; hence, different solvents used in a crystallization process might produce different patterns of hydrogen bonding networks, resulting in different crystal morphologies . Previous studies have shown that the crystals of organic compounds such as urea produced different habits depending on the solvents used. ,− Urea crystals grown in methanol produce unfavorable, long needle-like shapes with polar and nonpolar facets.…”

Section: Introductionmentioning

confidence: 99%

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

Shahrir

Yusop

Anuar

et al. 2023

Self Cite

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.

“…The morphologically important faces associated together with their growth layer thickness were identified and ranked by the BFDH method − using Mercury . Dominant intermolecular interactions, identified in the lattice energy calculations, were partitioned between the intrinsic (bulk) and extrinsic (surface-terminated) synthons , and the associated surface attachment energies calculated and, through this, the morphologies predicted (see further details in the Supporting Information, Section S5.2).…”

Section: Methodsmentioning

confidence: 99%

Role of Molecular, Crystal, and Surface Chemistry in Directing the Crystallization of Entacapone Polymorphs on the Au(111) Template Surface

Geatches

Hsiao

et al. 2023

Self Cite

The pharmaceutical compound entacapone ((E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide) is important in the treatment of Parkinson’s disease, exhibiting interesting polymorphic behavior upon crystallization from solution. It consistently produces its stable form A with a uniform crystal size distribution on the surface of an Au(111) template while concomitantly forming its metastable form D within the same bulk solution. Molecular modeling using empirical atomistic force-fields reveals more complex molecular and intermolecular structures for form D compared to form A, with the crystal chemistry of both polymorphs being dominated by van der Waals and π–π stacking interactions with lower contributions (ca. 20%) from hydrogen bonding and electrostatic interactions. Comparative lattice energies and convergence for the polymorphs are consistent with the observed concomitant polymorphic behavior. Synthon characterization reveals an elongated needle-like morphology for form D crystals in contrast to the more equant form A crystals with the surface chemistry of the latter exposing the molecules’ cyano groups on its {010} and {011} habit faces. Density functional theory modeling of surface adsorption reveals preferential interactions between Au and the synthon GA interactions of form A on the Au surface. Molecular dynamics modeling of the entacapone/gold interface reveals the entacapone molecular structure within the first adsorbed layer to show nearly identical interaction distances, for both the molecules within form A or D with respect to the Au surface, while in the second and third layers when entacapone molecule–molecule interactions overtake the interactions between those of molecule–Au, the intermolecular structures are found to be closer to the form A structure than form D. In these layers, synthon GA (form A) could be reproduced with just two small azimuthal rotations (5° and 15°) whereas the closest alignment to a form D synthon requires larger azimuthal rotations (15° and 40°). The cyano functional group interactions with the Au template dominate interfacial interactions with these groups being aligned parallel to the Au surface and with nearest neighbor distances to Au atoms more closely matching those in form A than form D. The overall polymorph direction pathway thus encompasses consideration of molecular, crystal, and surface chemistry factors.