Propensity of salicylamide and ethenzamide cocrystallization with aromatic carboxylic acids

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• 作者：Maciej Przybyłek^a ; Dorota Zió ; łkowska^b ; Karina Mroczyńska^c ; Piotr Cysewski^a ; ^{piotr.cysewski@cm.umk.pl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Salicylamide (PubChem CID ; 5147) ; Ethenzamide (PubChem CID ; 3282) ; Benzoic acid (PubChem CID ; 243) ; Salicylic acid (PubChem CID ; 338) ; Acetylsalicylic acid (PubChem CID ; 2244) ; 4-Acetamidobenzoic acid (PubChem CID ; 19266) ; 2 ; 6-Dihydroxybenzoic acid (PubChem CID ; 9338) ; 3 ; 4-Dihydroxybenzoic acid (PubChem CID ; 72) ; 2 ; 4-Dihydroxybenzoic acid (PubChem CID ; 1491) ; 4-Hydroxybenzoic acid (PubChem CID ; 135)
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：31 March 2016
• 年：2016
• 卷：85
• 期：Complete
• 页码：132-140
• 全文大小：1030 K

文摘

The cocrystallization of salicylamide (2-hydroxybenzamide, SMD) and ethenzamide (2-ethoxybenzamide, EMD) with aromatic carboxylic acids was examined both experimentally and theoretically. The supramolecular synthesis taking advantage of the droplet evaporative crystallization (DEC) technique was combined with powder diffraction and vibrational spectroscopy as the analytical tools. This led to identification of eleven new cocrystals including pharmaceutically relevant coformers such as mono- and dihydroxybenzoic acids. The cocrystallization abilities of SMD and EMD with aromatic carboxylic acids were found to be unexpectedly divers despite high formal similarities of these two benzamides and ability of the R2,2(8) heterosynthon formation. The source of diversities of the cocrystallization landscapes is the difference in the stabilization of possible conformers by adopting alternative intramolecular hydrogen boding patterns. The stronger intramolecular hydrogen bonding the weaker affinity toward intermolecular complexation potential. The substituent effects on R2,2(8) heterosynthon properties are also discussed.