TY - JOUR
T1 - anti/gauche Conformations Lead to Polymorphism in Homologous Phenylalkylamino-Nicotinic Acids
AU - Zhoujin, Yunping
AU - Li, Yuping
AU - Liang, Peng Yu
AU - Zhou, Pan Pan
AU - Parkin, Sean
AU - Li, Tonglei
AU - Yu, Faquan
AU - Long, Sihui
N1 - Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/5/3
Y1 - 2023/5/3
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.cgd.2c01319
DO - 10.1021/acs.cgd.2c01319
M3 - Article
AN - SCOPUS:85152711611
SN - 1528-7483
VL - 23
SP - 3154
EP - 3163
JO - Crystal Growth and Design
JF - Crystal Growth and Design
IS - 5
ER -