The urea-barbituric acid polymorphic co-crystal system: Characterization, thermodynamics and crystallization

Chasing the Co-crystal Disappearing Polymorph with Ab Initio Methods

“…The first analyzed stability rule, the density rule, , tends to be in agreement with the previous results. − For both temperatures (100 K and RT), P­(I) has the highest density among UBA polymorphs, suggesting that it is the most thermodynamically stable form (Table S2). However, it is often overlooked that the density rule applies only for materials without direct oriented interactions such as hydrogen bonds (HBs). , As a result, the rule should not be the base of stability assessment for most of the co-crystals.…”

“…Although the author refers to the P­(II) form as the metastable one, no computations confirming such statement were done. In the subsequent work of Zhang et al, cooling crystallization did not enable the reproduction of the P­(II) phase. In line with the previous experimental efforts, the performed DSC measurements confirmed that out of concomitant P­(I) and P­(III) polymorphs, the first one should be more stable in the temperature range below 306 K. Above this temperature, P­(III) seems to be more kinetically stabilized with slightly higher decomposition temperature .…”

“…To overcome these limitations, molecular dynamics methods were introduced to the studies of polymorphism. , Recently, metadynamics simulations , were used to analyze the disappearing conformational polymorph of succinic acid . In our studies, Born–Oppenheimer molecular dynamics (BOMD) calculations were used to investigate the self-assembly and stability of three urea–barbituric acid (UBA) polymorphs. , The BOMD results were compared with the analysis of H-bond propensities, coordination scores (CS), and the previous experimental data in the context of known thermodynamic stability rules. , Despite numerous experimental and theoretical trials, the “metastability” of the polar UBA polymorph is still unclear. − To our knowledge, UBA form (II) can be called one of the first known examples of disappearing co-crystal polymorphs.…”

Chasing the Co-crystal Disappearing Polymorph with Ab Initio Methods

“…DSC and TG measurements were previously performed for P(I) and P(III) of UBA polymorphs. 4,5 In line with Zhang et al 4 results, the small endothermic peak preceding the higher exothermic one was observed for P(I) near 185 °C (Figure S20). A similar thermal characteristic was detected in the DSC profile for disappearing P(II) form, although shifted to higher temperatures.…”

In Situ Analysis of Lactose Crystal in Solution through Slurry Flow Cell X‐Ray Diffraction

“…[4,5] These techniques include differential scanning calorimetry, X-ray powder diffraction, isothermal microcalorimetry, dynamic vapor sorption, and near infrared and Raman spectroscopy. [6][7][8] Process video microscopy was used for understanding particle size, particle shape, and particle population, but it was not in the way of in situ visualization of crystallization process. [9] In situ environmentally controlled atomic force microscopy could realize the real-time imaging of crystallization processes at a nanoscopic level, which was confined by its visual field.…”