{"title":"氨甲环酸药物的固态多功能性:新盐和共晶的结构和热行为。","authors":"Sunil Kumar Nechipadappu, Sridhar Balasubramanian","doi":"10.1107/S2052520622011969","DOIUrl":null,"url":null,"abstract":"<p><p>Tranexamic acid (TNA) is an anti-fibrinolytic hemostatic drug widely used in various medical treatments. Six new salts and five cocrystals of TNA are reported here and the crystal structures of the obtained multicomponent compounds were determined using single-crystal X-ray diffraction (SC-XRD) techniques. TNA formed salts with coformers maleic acid (MEA), nicotinic acid, DL-mandelic acid and saccharin. Salt formation with MEA resulted in three different solid forms, namely TNA-MEA (1:1), TNA-MEA (2:1) and TNA-MEA-H<sub>2</sub>O (1:1:1). All synthesized TNA salt structures were crystallized as anhydrous except for TNA-MEA-H<sub>2</sub>O (1:1:1). TNA formed cocrystals with phenolic coformers such as catechol (CAT), resorcinol, hydroquinone, pyrogallol (PRG) and phloroglucinol. All cocrystal structures crystallized as hydrates except for TNA-PRG (1:1). The detailed structural investigation using SC-XRD revealed the presence of robust N-H...O and O-H...O hydrogen bonds in TNA salts and cocrystals. In TNA cocrystals, except for TNA-CAT-H<sub>2</sub>O (1:1:1), the coformer molecules interact with TNA molecules via bridged water molecules. In all the salt structures, TNA exists as cations, in which both carboxylic and amino groups are protonated (-COOH and -NH<sub>3</sub><sup>+</sup>), while in cocrystals TNA exists as zwitterions with total charge zero. All synthesized multicomponent compounds were further characterized by differential scanning calorimetric, thermogravimetric and Fourier transform infrared analyses, and the formation of new multicomponent compounds were assessed based on the melting temperatures, percentage weight loss and stretching frequencies, respectively, corresponding to TNA/coformer molecules. A powder X-ray diffraction study confirmed the bulk purity of the synthesized crystalline multicomponent compounds.</p>","PeriodicalId":7320,"journal":{"name":"Acta crystallographica Section B, Structural science, crystal engineering and materials","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Solid-state versatility in tranexamic acid drug: structural and thermal behavior of new salts and cocrystals.\",\"authors\":\"Sunil Kumar Nechipadappu, Sridhar Balasubramanian\",\"doi\":\"10.1107/S2052520622011969\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Tranexamic acid (TNA) is an anti-fibrinolytic hemostatic drug widely used in various medical treatments. Six new salts and five cocrystals of TNA are reported here and the crystal structures of the obtained multicomponent compounds were determined using single-crystal X-ray diffraction (SC-XRD) techniques. TNA formed salts with coformers maleic acid (MEA), nicotinic acid, DL-mandelic acid and saccharin. Salt formation with MEA resulted in three different solid forms, namely TNA-MEA (1:1), TNA-MEA (2:1) and TNA-MEA-H<sub>2</sub>O (1:1:1). All synthesized TNA salt structures were crystallized as anhydrous except for TNA-MEA-H<sub>2</sub>O (1:1:1). TNA formed cocrystals with phenolic coformers such as catechol (CAT), resorcinol, hydroquinone, pyrogallol (PRG) and phloroglucinol. All cocrystal structures crystallized as hydrates except for TNA-PRG (1:1). The detailed structural investigation using SC-XRD revealed the presence of robust N-H...O and O-H...O hydrogen bonds in TNA salts and cocrystals. In TNA cocrystals, except for TNA-CAT-H<sub>2</sub>O (1:1:1), the coformer molecules interact with TNA molecules via bridged water molecules. In all the salt structures, TNA exists as cations, in which both carboxylic and amino groups are protonated (-COOH and -NH<sub>3</sub><sup>+</sup>), while in cocrystals TNA exists as zwitterions with total charge zero. All synthesized multicomponent compounds were further characterized by differential scanning calorimetric, thermogravimetric and Fourier transform infrared analyses, and the formation of new multicomponent compounds were assessed based on the melting temperatures, percentage weight loss and stretching frequencies, respectively, corresponding to TNA/coformer molecules. A powder X-ray diffraction study confirmed the bulk purity of the synthesized crystalline multicomponent compounds.</p>\",\"PeriodicalId\":7320,\"journal\":{\"name\":\"Acta crystallographica Section B, Structural science, crystal engineering and materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2023-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta crystallographica Section B, Structural science, crystal engineering and materials\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1107/S2052520622011969\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta crystallographica Section B, Structural science, crystal engineering and materials","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1107/S2052520622011969","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
摘要
氨甲环酸(TNA)是一种广泛应用于各种医学治疗的抗纤溶止血药物。本文报道了六种新的TNA盐和五种TNA共晶,并利用单晶x射线衍射(SC-XRD)技术测定了所得多组分化合物的晶体结构。TNA与顺形物马来酸(MEA)、烟酸、dl -扁桃酸和糖精形成盐。MEA成盐可形成三种不同的固体形态,即TNA-MEA(1:1)、TNA-MEA(2:1)和TNA-MEA- h2o(1:1:1)。除TNA- mea - h2o(1:1:1)外,所有合成的TNA盐结构均为无水结晶。TNA与儿茶酚(CAT)、间苯二酚、对苯二酚、邻苯三酚(PRG)和间苯三酚等酚类共构象形成共晶。除TNA-PRG(1:1)外,所有共晶结构均为水合物。利用SC-XRD对其进行了详细的结构研究,发现其具有坚固的N-H…O和O- h…TNA盐和共晶中的O氢键。在TNA共晶中,除TNA- cat - h2o(1:1:1)外,共晶分子通过桥接水分子与TNA分子相互作用。在所有的盐结构中,TNA都以阳离子形式存在,羧基和氨基都被质子化(-COOH和-NH3+),而在共晶中,TNA以两性离子形式存在,总电荷为零。通过差示扫描量热法、热重法和傅里叶变换红外分析对合成的多组分化合物进行了进一步表征,并根据TNA/共成体分子对应的熔融温度、失重百分比和拉伸频率对新合成的多组分化合物进行了评价。粉末x射线衍射研究证实了合成的晶体多组分化合物的体积纯度。
Solid-state versatility in tranexamic acid drug: structural and thermal behavior of new salts and cocrystals.
Tranexamic acid (TNA) is an anti-fibrinolytic hemostatic drug widely used in various medical treatments. Six new salts and five cocrystals of TNA are reported here and the crystal structures of the obtained multicomponent compounds were determined using single-crystal X-ray diffraction (SC-XRD) techniques. TNA formed salts with coformers maleic acid (MEA), nicotinic acid, DL-mandelic acid and saccharin. Salt formation with MEA resulted in three different solid forms, namely TNA-MEA (1:1), TNA-MEA (2:1) and TNA-MEA-H2O (1:1:1). All synthesized TNA salt structures were crystallized as anhydrous except for TNA-MEA-H2O (1:1:1). TNA formed cocrystals with phenolic coformers such as catechol (CAT), resorcinol, hydroquinone, pyrogallol (PRG) and phloroglucinol. All cocrystal structures crystallized as hydrates except for TNA-PRG (1:1). The detailed structural investigation using SC-XRD revealed the presence of robust N-H...O and O-H...O hydrogen bonds in TNA salts and cocrystals. In TNA cocrystals, except for TNA-CAT-H2O (1:1:1), the coformer molecules interact with TNA molecules via bridged water molecules. In all the salt structures, TNA exists as cations, in which both carboxylic and amino groups are protonated (-COOH and -NH3+), while in cocrystals TNA exists as zwitterions with total charge zero. All synthesized multicomponent compounds were further characterized by differential scanning calorimetric, thermogravimetric and Fourier transform infrared analyses, and the formation of new multicomponent compounds were assessed based on the melting temperatures, percentage weight loss and stretching frequencies, respectively, corresponding to TNA/coformer molecules. A powder X-ray diffraction study confirmed the bulk purity of the synthesized crystalline multicomponent compounds.
期刊介绍:
Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials publishes scientific articles related to the structural science of compounds and materials in the widest sense. Knowledge of the arrangements of atoms, including their temporal variations and dependencies on temperature and pressure, is often the key to understanding physical and chemical phenomena and is crucial for the design of new materials and supramolecular devices. Acta Crystallographica B is the forum for the publication of such contributions. Scientific developments based on experimental studies as well as those based on theoretical approaches, including crystal-structure prediction, structure-property relations and the use of databases of crystal structures, are published.