Apigenin Cocrystals: From Computational Prescreening to Physicochemical Property Characterization

Apigenin (4′,5,7-trihydroxyflavone, APG) has many potential therapeutic benefits; however, its poor aqueous solubility has limited its clinical applications. In this work, a large scale cocrystal screening has been conducted, aiming to discover potential APG cocrystals for enhancement of its solubility and dissolution rate. In order to reduce the number of the experimental screening tests, three computational prescreening tools, i.e., molecular complementarity (MC), hydrogen bond propensity (HBP), and hydrogen bond energy (HBE), were used to provide an initial selection of 47 coformer candidates, leading to the discovery of seven APG cocrystals. Among them, six APG cocrystal structures have been determined by successful growth of single crystals, i.e., apigenin–carbamazepine hydrate 1:1:1 cocrystal, apigenin–1,2-di(pyridin-4-yl)ethane hydrate 1:1:1 cocrystal, apigenin–valerolactam 1:2 cocrystal, apigenin-(dl) proline 1:2 cocrystal, apigenin-(d) proline/(l) proline 1:1 cocrystal. All of the APG cocrystals showed improved dissolution performances with the potential to be formulated into drug products

Micromechanical Interactions between Clathrate Hydrate Particles and Water Droplets: Experiment and Modeling

The micromechanical interactions between hydrate particles and unconverted water droplets play an important role in determining hydrate agglomeration, which is a key cause of hydrate blockages. In this study, the interaction behaviors between cyclopentane hydrate particles and water droplets in different conditions were directly investigated using a micromechanical force apparatus. For a smaller extent of subcooling, no hydrate was visibly converted from the water droplet during the measurement. A modified theoretical model was proposed to predict the corresponding interaction behavior. A parabolic approximation was found to be adequate for describing the liquid bridge shape. The insignificant change in the interfacial area between the liquid and the hydrate as the separation distance varied suggests the presence of a strong wetting hysteresis between liquid bridges and hydrate particles. The capillary force model can predict the interaction force with satisfactory accuracy. At a higher level of subcooling, the amount of hydrate converted from water droplets during the interaction led to a reduction in liquid volume and to dynamic changes in the boundary. The theoretical model presented here is not adequate for this specific case. Furthermore, a lower temperature induces more hydrate formation during measurement, which can increase the adhesion force. Compared with cohesion forces between a hydrate particle and a particle, adhesion forces between a hydrate particle and a droplet should dominate hydrate agglomeration. The present experiment and modeling contributes an improvement to the current understanding of hydrate agglomeration, leading to new potential strategies to control this process

Investigating Gas Hydrate Formation in Moderate to High Water Cut Crude Oil Containing Arquad and Salt, Using Differential Scanning Calorimetry

Gas hydrate formation can result in the blockage of deepwater flowlines, leading to severe economic and safety risks. As oil and gas production moves to greater water depths, the operating conditions of high pressure and low temperature can lead to greater risks of hydrate formation in the flowlines. In addition, as the fields mature, the continuous increase of water cut further enhances the potential problems associated with hydrate formation. With these more challenging production conditions, antiagglomerants could offer an economical and environmentally attractive alternative for preventing hydrate plug formation. However, reported work on hydrate antiagglomerant behavior for moderate to high water content systems is quite limited. The work reported in this paper investigates the effects of Arquad 2HT-75 (used as a model antiagglomerant) and salt (NaCl) on water-in-oil emulsions, and explores the gas hydrate formation characteristics for moderate to high water content (50 and 75 vol %) crude oil using high-pressure differential scanning calorimetry (DSC). The results indicate that the formation and dissociation of both ice and hydrate could lead to destabilization of the water-in-oil emulsion under certain conditions. At a high water cut (75 vol %), hydrate conversion is much lower, because of mass-transfer limitations for hydrate formation. Furthermore, the DSC and bottle tests also suggest that, at the concentrations and conditions used in this work, the addition of salt to Arquad 2HT-75 can help to form stable water-in-oil emulsions

Counteranion-Stabilized Titanium(IV) Isopolyoxocationic Clusters Isolated from Water

A novel titanium­(IV) oxo cluster comprised solely of Ti, O, and H atoms, [Ti₆(O_μ)₈(O_<i>t</i>H₂)₂₀]⁸⁺ (<b>Ti</b>_<b>6</b>) was synthesized in high yield via controlled hydrolysis and condensation of TiX₄ (X = Cl, Br) in the presence of TBAX (TBA = tetrabutylammonium; X = Cl, Br) from water, while reactions of TiI₄ and TBAI yielded [Ti₈O₁₂(OH₂)₂₄]⁸⁺ (<b>Ti</b>_<b>8</b>). The structures and compositions of the clusters were determined by single-crystal X-ray crystallography, powder X-ray diffraction, inductively coupled plasma atomic emission spectrometry, and energy-dispersive spectrometry. <b>Ti</b>_<b>6</b> is comprised of six-coordinated titanium­(IV) atoms bridged with μ₂-O atoms, structurally similar to a typical Lindqvist polyoxometalate. On the basis of a structural comparison of <b>Ti</b>_<b>6</b> and <b>Ti</b>_<b>8</b>, density functional theory calculations, and spectroscopic analysis, it is evident that both clusters are stabilized by halide counteranions via the formation of hydrogen bonds. This study not only presents the second example of a titanium­(IV) isopolyoxocationic cluster isolated from water but also suggests that counteranions are generally important for synthesizing molecular fragments of titanium oxides

Counteranion-Stabilized Titanium(IV) Isopolyoxocationic Clusters Isolated from Water

A novel titanium­(IV) oxo cluster comprised solely of Ti, O, and H atoms, [Ti₆(O_μ)₈(O_<i>t</i>H₂)₂₀]⁸⁺ (<b>Ti</b>_<b>6</b>) was synthesized in high yield via controlled hydrolysis and condensation of TiX₄ (X = Cl, Br) in the presence of TBAX (TBA = tetrabutylammonium; X = Cl, Br) from water, while reactions of TiI₄ and TBAI yielded [Ti₈O₁₂(OH₂)₂₄]⁸⁺ (<b>Ti</b>_<b>8</b>). The structures and compositions of the clusters were determined by single-crystal X-ray crystallography, powder X-ray diffraction, inductively coupled plasma atomic emission spectrometry, and energy-dispersive spectrometry. <b>Ti</b>_<b>6</b> is comprised of six-coordinated titanium­(IV) atoms bridged with μ₂-O atoms, structurally similar to a typical Lindqvist polyoxometalate. On the basis of a structural comparison of <b>Ti</b>_<b>6</b> and <b>Ti</b>_<b>8</b>, density functional theory calculations, and spectroscopic analysis, it is evident that both clusters are stabilized by halide counteranions via the formation of hydrogen bonds. This study not only presents the second example of a titanium­(IV) isopolyoxocationic cluster isolated from water but also suggests that counteranions are generally important for synthesizing molecular fragments of titanium oxides

Counteranion-Stabilized Titanium(IV) Isopolyoxocationic Clusters Isolated from Water

A novel titanium­(IV) oxo cluster comprised solely of Ti, O, and H atoms, [Ti₆(O_μ)₈(O_<i>t</i>H₂)₂₀]⁸⁺ (<b>Ti</b>_<b>6</b>) was synthesized in high yield via controlled hydrolysis and condensation of TiX₄ (X = Cl, Br) in the presence of TBAX (TBA = tetrabutylammonium; X = Cl, Br) from water, while reactions of TiI₄ and TBAI yielded [Ti₈O₁₂(OH₂)₂₄]⁸⁺ (<b>Ti</b>_<b>8</b>). The structures and compositions of the clusters were determined by single-crystal X-ray crystallography, powder X-ray diffraction, inductively coupled plasma atomic emission spectrometry, and energy-dispersive spectrometry. <b>Ti</b>_<b>6</b> is comprised of six-coordinated titanium­(IV) atoms bridged with μ₂-O atoms, structurally similar to a typical Lindqvist polyoxometalate. On the basis of a structural comparison of <b>Ti</b>_<b>6</b> and <b>Ti</b>_<b>8</b>, density functional theory calculations, and spectroscopic analysis, it is evident that both clusters are stabilized by halide counteranions via the formation of hydrogen bonds. This study not only presents the second example of a titanium­(IV) isopolyoxocationic cluster isolated from water but also suggests that counteranions are generally important for synthesizing molecular fragments of titanium oxides