Crystal Growth & Design最新文献

{"title":"Investigating Additive Effects on α-Glycine Growth through the Measurement of Facet Specific Growth Rates.","authors":"Caroline Offiler, Roger J Davey, Aurora J Cruz-Cabeza, Thomas Vetter","doi":"10.1021/acs.cgd.5c00028","DOIUrl":"10.1021/acs.cgd.5c00028","url":null,"abstract":"<p><p>The presence of trace amounts of additives during crystal growth can have a significant impact on the physical properties of the crystallizing substrate (e.g., crystal morphology, purity, polymorphic phase, or growth kinetics). In this work, we report the growth of α-glycine crystals (α-gly) in the presence of a variety of diverse additives: two l-amino acids, two organic acids, α-iminodiacetic acid, and two chloride salts. Growth rate data from imaging, together with analytical techniques such as X-ray photoelectron spectroscopy (XPS) and fluorescence microscopy, are used to observe which facet growth is impacted by the additive and to what extent. Relating these findings to the α-gly crystal structure provides explanations for the observed effects. Specifically, the growth inhibition of the (02̅0) facet α-gly in the presence of l-tryptophan and l-methionine shows how the prochirality of glycine results in two symmetrically equivalent facets growing at different rates. In the presence of malonic acid and salicylic acid, growth of the {011} facets is inhibited as a result of the interaction of deprotonated acids at the {011} surfaces. We find α-iminodiacetic acid to be an extremely effective inhibitor of α-gly, stopping the growth of both the {011} and {020} facets. We correlate the effectiveness of α-iminodiacetic acid to its structural similarity to gly, allowing it to easily block the growth of two α-gly facets. Finally, we observe the incorporation of the metal ions Fe(II), Cu(II), and Zn(II) into the {011} facets of α-gly. Interestingly, in the cases of Cu(II) and Zn(II), the incorporation of the metals into the α-gly lattice does not cause a noticeable change in the growth rates. The formation of coordination complexes containing the metal ions and glycine ligands allows for the observed incorporation of the metals into the α-gly lattice with limited disturbance to its crystal growth.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 5","pages":"1644-1652"},"PeriodicalIF":3.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating Additive Effects on α-Glycine Growth through the Measurement of Facet Specific Growth Rates","authors":"Caroline Offiler,&nbsp;Roger J. Davey,&nbsp;Aurora J. Cruz-Cabeza* and Thomas Vetter*,&nbsp;","doi":"10.1021/acs.cgd.5c0002810.1021/acs.cgd.5c00028","DOIUrl":"https://doi.org/10.1021/acs.cgd.5c00028https://doi.org/10.1021/acs.cgd.5c00028","url":null,"abstract":"<p >The presence of trace amounts of additives during crystal growth can have a significant impact on the physical properties of the crystallizing substrate (e.g., crystal morphology, purity, polymorphic phase, or growth kinetics). In this work, we report the growth of α-glycine crystals (α-gly) in the presence of a variety of diverse additives: two <span>l</span>-amino acids, two organic acids, α-iminodiacetic acid, and two chloride salts. Growth rate data from imaging, together with analytical techniques such as X-ray photoelectron spectroscopy (XPS) and fluorescence microscopy, are used to observe which facet growth is impacted by the additive and to what extent. Relating these findings to the α-gly crystal structure provides explanations for the observed effects. Specifically, the growth inhibition of the (02̅0) facet α-gly in the presence of <span>l</span>-tryptophan and <span>l</span>-methionine shows how the prochirality of glycine results in two symmetrically equivalent facets growing at different rates. In the presence of malonic acid and salicylic acid, growth of the {011} facets is inhibited as a result of the interaction of deprotonated acids at the {011} surfaces. We find α-iminodiacetic acid to be an extremely effective inhibitor of α-gly, stopping the growth of both the {011} and {020} facets. We correlate the effectiveness of α-iminodiacetic acid to its structural similarity to gly, allowing it to easily block the growth of two α-gly facets. Finally, we observe the incorporation of the metal ions Fe(II), Cu(II), and Zn(II) into the {011} facets of α-gly. Interestingly, in the cases of Cu(II) and Zn(II), the incorporation of the metals into the α-gly lattice does not cause a noticeable change in the growth rates. The formation of coordination complexes containing the metal ions and glycine ligands allows for the observed incorporation of the metals into the α-gly lattice with limited disturbance to its crystal growth.</p><p >Growth rate data of α-glycine facets in the presence of a varied selection of additives is presented together with a molecular-level rationalization of the mechanisms.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 5","pages":"1644–1652 1644–1652"},"PeriodicalIF":3.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.cgd.5c00028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Coformer Substitution in Cocrystallization: Griseofulvin and Phenol Derivatives","authors":"Janine Lässer,&nbsp; and ,&nbsp;Doris E. Braun*,&nbsp;","doi":"10.1021/acs.cgd.5c0006510.1021/acs.cgd.5c00065","DOIUrl":"https://doi.org/10.1021/acs.cgd.5c00065https://doi.org/10.1021/acs.cgd.5c00065","url":null,"abstract":"<p >This study investigates the cocrystallization of griseofulvin with phenolic coformers, highlighting its feasibility and variability. In addition to the previously reported cocrystal of griseofulvin with 4-<i>t</i>-butylphenol (1:1), the experimental screening identified three new cocrystals: with phenol (2:5), 4-<i>t</i>-amylphenol (1:1), and 2,4,6-trichlorophenol (2:3). Phenols with carbon substituents in the <i>ortho</i> or <i>meta</i> positions failed to form cocrystals, likely due to steric hindrance and electron-donating effects. In contrast, phenols with chlorine substituents, particularly in the <i>ortho</i> and <i>para</i> positions, demonstrated enhanced cocrystallization potential, driven by the electron-withdrawing effects that promote hydrogen bonding. The 2:5 phenol cocrystal required optimized conditions for isolation and exhibited instability under ambient conditions due to coformer sublimation, a tendency also observed for the other cocrystals. While challenging, sublimation facilitated the determination of stoichiometric ratios, which varied from 1:1 to 2:3 and 2:5. Furthermore, this study provides a data set of cocrystal-forming and noncocrystal-forming combinations as a rigorous test case for virtual cocrystal prediction. Among the tested methods, crystal structure prediction proved the most reliable, identifying all observed cocrystal combinations and, together with powder X-ray diffraction, offering insights into the experimental coformer and cocrystal structures. Future integration of CSP with machine learning could accelerate prediction speed and accommodate a broader range of stoichiometric ratios. Overall, this work highlights the complexity and potential of cocrystallization.</p><p >This study demonstrates the cocrystallization feasibility between griseofulvin and selected phenolic coformers, identifying three new cocrystals with phenol, 4-<i>t</i>-amylphenol, and 2,4,6-trichlorophenol. The results emphasize the impact of substituent effects, sublimation tendencies, and stoichiometric variability on cocrystal formation and stability. The dataset serves as a critical benchmark for virtual prediction tools, showcasing both the potential and limitations of <i>in silico</i> cocrystal screening approaches.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 5","pages":"1688–1707 1688–1707"},"PeriodicalIF":3.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.cgd.5c00065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Negative Linear Compressibility in the Elastically Flexible Crystal of Copper(II) Acetylacetonate","authors":"Yu Liu,&nbsp;Boyang Fu,&nbsp;Weilong He,&nbsp;Wenbo Qiu,&nbsp;Xiangting Ren,&nbsp;Panfeng Zhao* and Weizhao Cai*,&nbsp;","doi":"10.1021/acs.cgd.4c0149310.1021/acs.cgd.4c01493","DOIUrl":"https://doi.org/10.1021/acs.cgd.4c01493https://doi.org/10.1021/acs.cgd.4c01493","url":null,"abstract":"<p >The coordination compound copper(II) acetylacetonate, [Cu(acac)₂], exhibits remarkable elastic flexibility due to the reversible rotation of molecules when the crystal is twisted or bent without loss of its crystallinity. The effects of external stimuli, including heat and strain, have been intensively studied on this material, but its mechanical response to the pressure has not yet been reported. Using the high-pressure single-crystal X-ray diffraction method, we show the herringbone-type [Cu(acac)₂] demonstrates remarkable structural changes in molecular orientations toward the (001) plane under compression, without the occurrence of phase transitions. The alterations in molecular packing arrangements result in the emergence of unusual negative linear compressibility (NLC) of −6.2(6) TPa^–1 along the <i>b</i> axis over the pressure range of 0.1 MPa–6.19 GPa. Moreover, synchrotron powder X-ray diffraction and Raman spectroscopy measurements demonstrate that the ambient-pressure phase is robust and can be stabilized at least to 10 GPa. In addition, the bandgap exhibits a slight reduction of ∼0.2 eV as the pressure is increased to 10.10 GPa, and the sample returns to its original state upon complete pressure release. Our findings suggest that the NLC behavior may be present in a diverse range of unidentified herringbone-type molecular crystals, which differs from the extensively researched hinged wine-rack frameworks.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 5","pages":"1423–1431 1423–1431"},"PeriodicalIF":3.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multicomponent Solid Forms of Pioglitazone and Their Influence on Drug Dissolution","authors":"Naoki Shimada,&nbsp;Haruka Uchida,&nbsp;Vasanthi Palanisamy,&nbsp;Vladimir Chernyshev* and Toshiro Fukami*,&nbsp;","doi":"10.1021/acs.cgd.4c0161710.1021/acs.cgd.4c01617","DOIUrl":"https://doi.org/10.1021/acs.cgd.4c01617https://doi.org/10.1021/acs.cgd.4c01617","url":null,"abstract":"<p >Pioglitazone (PIO), a type 2 diabetes medication, effectively decreases blood glucose levels. It exhibits poor aqueous solubility and falls in the category of the biopharmaceutics classification system (BCS)-II. To enhance solubility and dissolution characteristics of the lipophilic drug, cocrystallization with organic acids such as 2-naphthalenesulfonoic acid (NSA), oxalic acid (OXA), maleic acid (MLE), and dihydroxy benzoic acid (DHBA) were successfully carried out via the solvent-drop grinding method. The multicomponent solid forms were characterized by powder X-ray diffraction (PXRD), infrared spectroscopy, and thermal analysis. The crystal structures of the PIO–NSA and PIO–MLE solid forms were obtained through Rietveld refinement from the high-resolution PXRD data as their crystallization was challenging. The N–H···N hydrogen-bonded PIO homodimer in the drug is replaced by the O–H···N neutral hydrogen bond in the cocrystal monohydrate (PIO–NSA 1:1:1) and N⁺–H···O^– ionic interactions in the salt hemihydrate (PIO–MLE 1:1:0.5). Spectroscopic analysis confirmed the formation of 1:1 salts between PIO and OXA/DHBA. However, the structural prediction was compromised due to the nonmonophasic behavior of these salts. Solubility of novel multicomponent solid forms was performed in pH 6.8 phosphate buffer at 37 °C and determined using UV–vis spectroscopy. The PIO–NSA cocrystal hydrate dissolved 7 times compared to PIO, which may be useful for further pharmaceutical application during drug formulation. The solubility data was correlated with the synthon modulation, lower melting point, and coformer solubility.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 5","pages":"1514–1525 1514–1525"},"PeriodicalIF":3.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Double Salt Formation on Diastereoisomeric Crystallization of Mefloquine with Propionic and Succinic Acid Derivatives: A Structural Study of Chiral Nondiscrimination","authors":"Paulo S. Carvalho Jr.*,&nbsp;Juan Carlos Tenorio and Luan F. Diniz,&nbsp;","doi":"10.1021/acs.cgd.4c0104010.1021/acs.cgd.4c01040","DOIUrl":"https://doi.org/10.1021/acs.cgd.4c01040https://doi.org/10.1021/acs.cgd.4c01040","url":null,"abstract":"<p >The diastereomeric resolution remains a challenging endeavor due to the intricate interplay of experimental parameters and the inherent variability of crystallization outcomes. Understanding of the enantiomer’s discrimination leading to the formation of the diastereomeric double salts was investigated for mefloquine (Mf), a racemic antimalarial drug. A series of nine diastereomeric double salts and their racemic counterparts were synthesized by combining racemic Mf with propionic and succinic acid derivatives. All materials were characterized by differential scanning calorimetry, thermogravimetry, and single-crystal X-ray diffraction. The salts were designed to exploit the NH⁺···COO^– H-bond to create the salts. This resulted in a diverse range of crystal packing arrangements. The complexity of the packing of the double salt structure includes a high <i>Z</i>’ parameter, hydration, conformational, and synthon multiplicity. In comparison to the pure racemic counterparts, the double salt structures exhibit isostructurality and/or isomorphism. From thermal behavior and solubility data, it is noticed that the pure racemate is still the most stable state, and double salts occur, in general, as an attempt to imitate or achieve the pure racemic structure.</p><p >Racemic and diastereoisomeric double salts of mefloquine were synthesized and their crystal structures elucidated. A comprehensive analysis of chiral recognition and molecular self-assembly in relation to varying molecular size and chirality is presented.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 5","pages":"1315–1329 1315–1329"},"PeriodicalIF":3.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.cgd.4c01040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppression of Screw Dislocation-Induced Hillocks in MOCVD-Grown α-Ga2O3 on m-Plane Sapphire by Introducing a High-Temperature Buffer","authors":"Zhucheng Li,&nbsp;Xiaodong Zhang*,&nbsp;Li Zhang,&nbsp;Tiwei Chen,&nbsp;Gaofu Guo,&nbsp;Dengrui Zhao,&nbsp;Yu Hu,&nbsp;Zhili Zou,&nbsp;Huanyu Zhang,&nbsp;Kun Xu,&nbsp;Feng Yang,&nbsp;Guangyuan Yu,&nbsp;Wenxiang Mu*,&nbsp;Zhongming Zeng and Baoshun Zhang,&nbsp;","doi":"10.1021/acs.cgd.4c0147210.1021/acs.cgd.4c01472","DOIUrl":"https://doi.org/10.1021/acs.cgd.4c01472https://doi.org/10.1021/acs.cgd.4c01472","url":null,"abstract":"<p >α-Gallium oxide (Ga₂O₃) has great potential in the applications of high-power, high-frequency, and energy-saving electronic devices. In this study, we successfully grew pure-phase α-Ga₂O₃ films on m-plane sapphire substrates by using metal organic chemical vapor deposition (MOCVD) and systematically investigated the impact of various growth parameters on the resulting film characteristics. The crystallization quality of the films improved by adjusting the VI/III ratio, ultimately yielding a symmetric rocking curve full width at half-maximum (fwhm) of 0.39° for the (300) diffraction. The surface morphology of α-Ga₂O₃ films exhibited a layer-by-layer growth mode, characterized by a remarkably flat surface (RSM = 0.365 nm) in the early growth stage. Nevertheless, as the film thickness increased, the appearance of hillock defects composed of β-Ga₂O₃ detrimentally impacted the surface quality. To mitigate this issue, a high-temperature buffer layer was introduced to inhibit the formation of hillocks. This approach resulted in α-Ga₂O₃ films on m-plane sapphire with substantial thickness and exceptional surface quality, establishing a robust foundation for the future fabrication of heterojunction devices.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 5","pages":"1406–1414 1406–1414"},"PeriodicalIF":3.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Polymorphism and Phase Stability of Hydrated Magnesium Carbonate Nesquehonite MgCO₃·3H₂O: Negative Axial Compressibility and Thermal Expansion in a Cementitious Material\".","authors":"David Santamaría-Pérez, Raquel Chuliá-Jordán, Javier Gonzalez-Platas, Alberto Otero-Dela-Roza, Javier Ruiz-Fuertes, Julio Pellicer-Porres, Robert Oliva, Catalin Popescu","doi":"10.1021/acs.cgd.5c00115","DOIUrl":"10.1021/acs.cgd.5c00115","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1021/acs.cgd.3c01171.].</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 5","pages":"1724"},"PeriodicalIF":3.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Evolution and Cu Diffusion Mechanism in Bi2Se3 Thin Films on YBa2Cu3O7 as a Function of Cracked-Se Processing Time","authors":"Woo-Jung Lee*,&nbsp;Dae-Hyung Cho,&nbsp;Tae-Ha Hwang,&nbsp;Jin Young Maeng,&nbsp;Kwangsik Jeong,&nbsp;So-Young Lim,&nbsp;Rina Kim,&nbsp;Yong-Duck Chung and Jonghyun Song,&nbsp;","doi":"10.1021/acs.cgd.4c0151810.1021/acs.cgd.4c01518","DOIUrl":"https://doi.org/10.1021/acs.cgd.4c01518https://doi.org/10.1021/acs.cgd.4c01518","url":null,"abstract":"<p >This study provides a comprehensive investigation into the fabrication and interface chemistry of a heterojunction between yttrium barium copper oxide (YBa₂Cu₃O₇, YBCO), a high-temperature superconductor (HTS), and bismuth selenide (Bi₂Se₃), a prototypical topological insulator (TI). Bi₂Se₃ thin films were deposited on YBCO using a controlled cracked-Se process with varying durations to optimize crystallographic and chemical properties at the HTS/TI interface. Various analytical techniques were employed to systematically characterize the morphological evolution and phase transitions of Bi₂Se₃ on YBCO. Notably, extended cracked-Se process time substantially enhanced the crystallinity of Bi₂Se₃, as evidenced by the emergence of distinct Raman-active vibrational modes and a well-defined <i>c</i>-axis orientation. In addition, the cracked-Se process facilitated the diffusion of Cu atoms from YBCO into Bi₂Se₃, resulting in the formation of interstitial Cu atoms in the van der Waals gaps and Cu–Se bonds. These Cu-related chemical interactions were confirmed via depth-resolved X-ray photoemission spectroscopy, which revealed an expanded mixed interfacial layer with increasing cracked-Se process time. This study offers crucial insights into the complex interfacial dynamics between HTS and TI materials, emphasizing the pivotal role of Se crackers in modulating the structural and chemical characteristics of Bi₂Se₃ thin films. These findings are significant in advancing the integration of HTS/TI heterostructures into next-generation quantum devices.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 5","pages":"1439–1447 1439–1447"},"PeriodicalIF":3.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroED Structures of Fluticasone Furoate and Fluticasone Propionate Provide New Insights into Their Function","authors":"Jieye Lin,&nbsp;Johan Unge and Tamir Gonen*,&nbsp;","doi":"10.1021/acs.cgd.4c0168310.1021/acs.cgd.4c01683","DOIUrl":"https://doi.org/10.1021/acs.cgd.4c01683https://doi.org/10.1021/acs.cgd.4c01683","url":null,"abstract":"<p >The detailed understanding of the conformational pathway of fluticasone, a widely prescribed medicine for allergic rhinitis, asthma, and chronic obstructive pulmonary disease (COPD), from formulation to its protein-bound state, has been limited due to a lack of access to its high-resolution structures. The three-dimensional (3D) structure of fluticasone furoate <b>1</b> remains unpublished, and the deposited structure of fluticasone propionate <b>2</b> could be further refined due to refinement against new data. We applied microcrystal electron diffraction (MicroED) to determine the 3D structures of <b>1</b> and <b>2</b> in their solid states. The preferred geometries in solution were predicted by using density functional theory (DFT) calculations. A comparative analysis of the structures of <b>1</b> and <b>2</b> across three states (in solid state, in solution, and protein-bound conformation) revealed the course of the conformational changes during the entire transition. Potential energy plots were calculated for the most dynamic bonds, uncovering their rotational barriers. This study underscores the combined use of MicroED and DFT calculations to provide a comprehensive understanding of conformational and energy changes during drug administration. The quantitative comparison also highlights the subtle structural differences that may lead to significant changes in the pharmaceutical properties.</p><p >The 3D structures of fluticasone furoate <b>1</b> and fluticasone propionate <b>2</b> in solid states were solved by microcrystal electron diffraction (MicroED). A comparative analysis of the structures of <b>1</b> and <b>2</b> across three states (in the solid state, in solution, and in the protein-bound conformation) revealed the conformational and energy changes during drug administration.</p>","PeriodicalId":34,"journal":{"name":"Crystal Growth & Design","volume":"25 5","pages":"1588–1596 1588–1596"},"PeriodicalIF":3.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.cgd.4c01683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}