Thermodynamic solubility of celecoxib in organic solvents

The present work investigates the solubility of the stable polymorph of celecoxib (CEL) drug in a range of pure organic solvents, including methanol, isopropanol, butanol, ethyl acetate, acetonitrile and toluene,...

Synthetic control over polymorph formation in the d-band semiconductor system FeS2

Pyrite, also known as fool's gold is the thermodynamic stable polymorph of FeS2.

Crystal structure of a 1:1 co-crystal of the anticancer drug gefitinib with azelaic acid

In the title co-crystal, C22H24ClFN4O3·C9H16O4, gefitinib (GTB; systematic name: quinazolin-4-amine) co-crystallizes with azelaic acid (AA; systematic name: nonanedioic acid). The co-crystal has the monoclinic P21/n centrosymmetric space group, containing one molecule each of GTB and AA in the asymmetric unit. A structure overlay of the GTB molecule in the co-crystal with that of its most stable polymorph revealed a significant difference in the conformation of the morpholine moiety. The significant deviation in the conformation of one of the acidic groups of azelaic acid from its usual linear chain structure could be due to the encapsulation of one acidic group in the pocket formed between the two pincers of GTB namely, the morpholine and phenyl moieties. Both GTB and AA molecules form N—H...O, O—H...N, C—H...O hydrogen bonds with C—H...F close contacts along with off-stacked aromatic π–π interactions between the GTB molecules.

Polymorph evolution during crystal growth studied by 3D electron diffraction

3D electron diffraction (3DED) has been used to follow polymorph evolution in the crystallization of glycine from aqueous solution. The three polymorphs of glycine which exist under ambient conditions follow the stability order β < α < γ. The least stable β polymorph forms within the first 3 min, but this begins to yield the α-form after only 1 min more. Both structures could be determined from continuous rotation electron diffraction data collected in less than 20 s on crystals of thickness ∼100 nm. Even though the γ-form is thermodynamically the most stable polymorph, kinetics favour the α-form, which dominates after prolonged standing. In the same sample, some β and one crystallite of the γ polymorph were also observed.

Bulk (in)stability as a possible source of surface reconstruction

A density functional theory-based study shows that surface energy stabilization reconstruction mechanisms of transition metal carbides and nitrides occur when featuring a crystal structure different from most stable polymorph, and driven by its instablity.

Study of the effect the rate of addition of the antisolvent on the crystallization of the CL-20

In this paper, the effect of antisolvent addition rate on the yield and polymorphic purity of the obtained product, in order to optimise the 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) precipitation process using a solvent/antisolvent system, was determined. It was found that increased dispensing rate of the antisolvent results in increased supersaturation in the mother liquor. This, in turn, increases the nucleation rate. The prevalence of the process of creating new seeds reduces the growth rate of the crystal, which affects the size distribution of the final crystallisation product. Reducing the time of the process results in the transformation of the initially formed, kinetically stable polymorph β, into the thermodynamically stable ε form with a lower yield, than the yield obtained after increased time.

Thermodynamic vs. Kinetic Basis for Polymorph Selection

Ratios of equilibrium solubilities rarely exceed two-fold for polymorph pairs. A model has been developed based on two intrinsic properties of polymorph pairs, namely the ratio of equilibrium solubilities of the individual pairs (C*me/C*st) and the ratio of interfacial energies (γst/γme) and one applied experimental condition, namely the supersaturation identifies which one of a pair of polymorphs nucleates first. A domain diagram has been developed, which identifies the point where the critical free energy of nucleation for the polymorph pair are identical. Essentially, for a system supersaturated with respect to both polymorphs, the model identifies that low supersaturation with respect to the stable polymorph (Sst) leads to an extremely small supersaturation with respect to the metastable polymorph (Sme), radically driving up the critical free energy with respect to the metastable polymorph. Generally, high supersaturations sometimes much higher than the upper limit of the metastable zone, are required to kinetically favour the metastable polymorph.

Synthesis and Adsorbing Properties of Tabular {001} Calcite Crystals

One of the most common crystal habits of the thermodynamically stable polymorph of calcium carbonate, calcite, is the rhombohedral one, which exposes {10.4} faces. When calcite is precipitated in the presence of Li+ ions, dominantly {00.1} faces appear together with the {10.4}, thus generating truncated rhombohedrons. This well-known phenomenon is explored in this work, with the aim of obtaining calcite crystals with smooth {00.1} faces. In order to achieve this objective, the formation of calcite was examined in precipitation systems with different c(Ca2+)/c(Li+) ratios and by performing an initial high-power sonication. At the optimal conditions, a precipitate consisting of thin, tabular {001} calcite crystals and very low content of incorporated Li+ has been obtained. The adsorption properties of the tabular crystals, in which the energetically unstable {00.1} faces represent almost all of the exposed surface, were tested with model dye molecules, calcein and crystal violet, and compared to predominantly rhombohedral crystals. It was found that the {00.1} crystals showed a lower adsorption capability when compared to the {10.4} crystals for calcein, while the adsorption of crystal violet was similar for both crystal morphologies. The obtained results open new routes for the usage of calcite as adsorbing substrates and are relevant for the understanding of biomineralization processes in which the {00.1} faces often interact with organic macromolecules.