Hierarchy of supramolecular synthons: Persistent hydrogen bonds between carboxylates and weakly acidic hydroxyl moieties in cocrystals of zwitterions

Padmini Kavuru, Dalia Aboarayes, Kapildev K. Arora, Heather D. Clarke, Alyssa Kennedy, Lissette Marshall, Tien Teng Ong, Jason Perman, Twarita Pujari, Łukasz Wojtas, Michael J. Zaworotko

Research output: Contribution to journalArticlepeer-review

Abstract

Whereas carboxylic acids are well explored in the context of cocrystals, the same cannot be said about carboxylate moieties. This Cambridge Structural Database (CSD) and experimental study demonstrates that carboxylate moieties persistently form charge-assisted H-bonds with weakly acidic hydroxyl moieties such as phenols. CSD statistics reveal that 58 of 103 relevant structures exhibit carboxylate-hydroxyl (phenolic) supramolecular heterosynthons even in the presence of competing functional groups. The following neutral cocrystal formers sustain 15 new cocrystals of zwitterions and their crystal structures reveal that all exhibit carboxylate-hydroxyl supramolecular heterosynthons: citric acid (CIT), l-ascorbic acid (ASC), hesperetin (HES), quercetin (QUE), resveratrol (RES), catechol (CAT), protocatechuic acid (PCA), ferulic acid (FER), ellagic acid (ELA), and gallic acid (GAL). Zwitterions used were betaine (BTN), sarcosine (SAR), dimethyl glycine (DMG), baclofen (BAC), nicotinic acid (NAC), and isonicotinic acid (INA). Carboxylate-hydroxyl supramolecular heterosynthons were observed as follows: 2-point carboxylate-vicinal diol R 22 (9) in ASCSAR, ASCNAC, and BTNASC; R4 4 (18) between two carboxylate and two catechol moieties in BTNGAL, ELASAR, and ELADMG; CITINA·2H2O, GALINA·H2O, and HESNAC (+ and ± forms) exhibit 1-point H-bonds.

Original languageEnglish
Pages (from-to)3568-3584
Number of pages17
JournalCrystal Growth and Design
Volume10
Issue number8
DOIs
Publication statusPublished - 4 Aug 2010
Externally publishedYes

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