Mechanistic study of the formation of arbutin polymorphs and solvates

Taiwaikuli, Mukaidaisi; Wang, Ting; Chen, Kui; Feng, Yaoguang; Xing, Jiangna; Huang, Xin; Wang, Na; Zhou, Lina; Hao, Hongxun

doi:10.1039/d2ce01670b

Cited by 5 publications

(4 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well-known that the molecular electrostatic potential (MEP) is widely used as a tool for identifying the sites of favorable interactions with other molecules. , As a result, we calculated the MEP of MPV and solvent molecules to analyze the formation mechanism of MPV solvates, as shown in Figure . Normally, molecules always prefer to approach each other in the electrostatic potential complementary manner . The MPV contains many positive and negative potential zones, which are the basis of forming the potential complementary with solvent molecules.…”

Section: Resultsmentioning

confidence: 99%

“…Normally, molecules always prefer to approach each other in the electrostatic potential complementary manner. 52 The MPV contains many positive and negative potential zones, which are the basis of forming the potential complementary with solvent molecules. Meanwhile, the global minimum value on MEP surfaces of solvent molecules is −36.62 (THF), −36.71 (EtOH), −36.44 (IPA), and −36.07 kcal/mol (IBA), respectively.…”

Section: Formation Mechanism Of Mpv Solvatesmentioning

confidence: 99%

See 1 more Smart Citation

Polymorphs and Solvates of Molnupiravir: Crystal Structures and Solid Forms Transformation Analysis

Han,

Wang,

Song

et al. 2024

Crystal Growth & Design

View full text Add to dashboard Cite

Molnupiravir (MPV) is a widely used oral anti-COVID-19 drug. Owing to the rotatable bonds and the large number of acceptors and donors of hydrogen bonds in the molecular structure of MPV, three pure polymorphs (forms I, II, and III) and four solvates (ethanol, isopropanol, isobutanol, and tetrahydrofuran) of MPV (MPV-EtOH, MPV-IPA, MPV-IBA, and MPV-THF) were obtained. Importantly, the crystal structures of form I and the four solvates were successfully determined by single-crystal X-ray diffraction for the first time. Interestingly, all solvates are isostructural and have very similar unit cell parameters. Meanwhile, the solvent molecules in their structures are all in the voids surrounded by MPV molecules, forming a channel structure that facilitates desolvation. The formation mechanism of the solvates was also investigated based on the molecular electrostatic potential and hydrogen-bond energy of possible synthons. Moreover, a detailed stability study of MPV was conducted by using thermal analysis and dynamic vapor sorption. Finally, the phase transformations of the different solid forms were summarized. Our study provides a comprehensive understanding of the crystal landscape of the MPV.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Formation Mechanism Of Mpv Solvatesmentioning

confidence: 99%

Polymorphs and Solvates of Molnupiravir: Crystal Structures and Solid Forms Transformation Analysis

Han,

Wang,

Song

et al. 2024

Crystal Growth & Design

View full text Add to dashboard Cite

show abstract

“…46,47 The monohydrate was obtained in the crystallization of organic solvents with water, which may be attributed to the two hydroxyl groups in water molecules, while differences in molecular sizes facilitate stable hydrogen bonding with the compound, promoting precipitation. [48][49][50] The 100 kg scale-up flowchart is depicted in Fig. 4, with Fig.…”

Section: Design and Scale-up Of Chiral Separationmentioning

confidence: 99%

Design and process study of chiral separation of (2S,4S)-1-(tert-butoxy carbonyl)-4-(methoxymethyl) pyrrolidine-2-carboxylic acid for green manufacturing

Ge,

Fu,

et al. 2024

Green Chem.

View full text Add to dashboard Cite

show abstract

“…It is common to obtain API crystals with different solid forms in different solvents. − Conversely, there are also some examples that the same solid form was obtained in the same solvent using different solid forms of APIs as the raw material. − Therefore, it is of great significance to study the mechanism of the effect of solvents on the solution crystallization process. Some studies have been conducted on the effect of different solvents on the form of products in solution crystallization. − However, most of these studies were focused only on the polarity and solubility properties of the solvents, and the mechanism of solvent effect on polymorphism still needs further investigation. Molecular dynamics (MD) simulation is a widely used analytical method to simulate the dynamic behavior of a large number of molecules.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic Study on the Effect of Solvents on Polymorphic Transformation of Aripiprazole by Solvent Property Parameters and Molecular Dynamics Simulation

Zheng,

Huang,

Wang

et al. 2024

Crystal Growth & Design

Self Cite

View full text Add to dashboard Cite

The choice of solvent is crucial in the drug crystallization process, and the mechanism of solvent effect on the crystallization results can be conducive to the selection of solvents. In this work, the effect of solvents on the suspension crystallization process of Aripiprazole (APZ) was explored by generalized solvent property parameters and molecular dynamics simulation. Eight different crystal products of APZ (Form III, Form IV, Form V, and five solvates) were obtained after suspension crystallization in 15 different solvents, in which APZ semiethylene glycol solvate (S EG ) is one newly discovered product, and its crystal structure was elucidated. Besides, the crystal transformation processes were studied using molecular dynamics simulations. Conformational search was also adopted to investigate the formation mechanisms of different forms. The results indicated that van der Waals interactions between the solute and solvents dominate the conformations of the APZ molecules in the solvents and further influence the crystal form of the products. However, the polymorphism of APZ in solvents with similar van der Waals interactions may also be different, suggesting that other solvent properties also influence the polymorphism results. Thus, the solvent property parameters were analyzed in detail, and the results indicated that in addition to the van der Waals interaction energy between the solvent molecules and the APZ molecules, the hydrogen bond donor propensity, the volume, the sphericity, and the cohesive energy density of the solvent molecules are also decisive for the suspension crystallization results of APZ. Finally, the mechanism of the effects of solvents species on the suspension crystallization results was proposed and discussed.

show abstract

Mechanistic study of the formation of arbutin polymorphs and solvates

Abstract: In this study, the complicated solvation behaviors of arbutin were studied from both experiment investigations and theoretical calculations. Six solid forms of arbutin including anhydrous Form I and five solvates...

Cited by 5 publications

References 37 publications

Polymorphs and Solvates of Molnupiravir: Crystal Structures and Solid Forms Transformation Analysis

Polymorphs and Solvates of Molnupiravir: Crystal Structures and Solid Forms Transformation Analysis

Design and process study of chiral separation of (2S,4S)-1-(tert-butoxy carbonyl)-4-(methoxymethyl) pyrrolidine-2-carboxylic acid for green manufacturing

Mechanistic Study on the Effect of Solvents on Polymorphic Transformation of Aripiprazole by Solvent Property Parameters and Molecular Dynamics Simulation

Contact Info

Product

Resources

About