anti/gauche Conformations Lead to Polymorphism in Homologous Phenylalkylamino-Nicotinic Acids

Yunping Zhoujin, Yuping Li, Peng Yu Liang, Pan Pan Zhou, Sean Parkin, Tonglei Li, Faquan Yu, Sihui Long

Research output: Contribution to journalArticlepeer-review


A series of phenylalkylamino-nicotinic acids (1-4) were synthesized by varying the length of the linker between the pyridine and benzene rings, and their polymorphism was investigated. Under the same crystallization conditions, one crystal form was found for compounds 1 and 2, three forms were obtained for compound 3, and two forms were harvested for compound 4. A detailed conformational analysis was performed, and the polymorphism of 3 and 4 was found to be caused by the anti and/or gauche conformation of specific sigma bonds within them. However, there appears to be no correlation between the number of polymorphs and sigma bonds, and the rotation of which sigma bond(s) is responsible for the polymorphism could not be predicted. Phase behavior studies by differential scanning calorimetry (DSC) revealed a phase transition from 4-I with a small asymmetric unit (Z′ = 1) to 4-II with a larger asymmetric unit (Z′ = 2). Computational studies including Hirshfeld surface analysis and independent gradient model (IGM) analyses were performed to highlight the most significant intermolecular interactions in the crystals.

Original languageEnglish
Pages (from-to)3154-3163
Number of pages10
JournalCrystal Growth and Design
Issue number5
StatePublished - May 3 2023

Bibliographical note

Publisher Copyright:
© 2023 American Chemical Society.

ASJC Scopus subject areas

  • General Chemistry
  • General Materials Science
  • Condensed Matter Physics


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