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Strong Hydrogen Bond Leads to a Fifth Crystalline Form and Polymorphism of Clonixin
Author(s) -
Long Sihui,
Mao Tengfei,
Chen Peng,
Liu Meng,
Parkin Sean,
Zhang Mingtao,
Li Tonglei,
Zhou Panpan,
Yu Faquan
Publication year - 2017
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201700947
Subject(s) - hydrogen bond , dihedral angle , crystallography , differential scanning calorimetry , chemistry , pyridine , polymorphism (computer science) , crystal structure , lattice energy , powder diffraction , raman spectroscopy , dimethylformamide , crystal (programming language) , crystal engineering , infrared spectroscopy , solvent , molecule , supramolecular chemistry , organic chemistry , physics , biochemistry , programming language , gene , genotype , computer science , optics , thermodynamics
Over 30 years since the discovery of four crystal forms ( I , II , III and IV ) of Clonixin [2‐(3‐chloro‐2‐methyl‐phenylamino)‐nicotinic acid], a fifth form, a dimethylformamide (DMF) solvate, has been obtained by crystal growth in DMF. The new form was characterized by single‐crystal X‐ray diffraction, FT‐IR, and Raman spectroscopy. The crystal structure is stabilized by the strong hydrogen bond between the carboxylic acid OH and the DMF carbonyl whose strength is on par with those of the four solvent‐free forms, which are based on either the acid‐acid homosynthon or the acid‐pyridine heterosynthon, depending on the dihedral angle between the two aromatic rings. This solvate loses DMF to convert into form I , as confirmed by differential scanning calorimetry (DSC) and powder X‐ray diffraction (PXRD). Other aspects of this polymorphic/solvatomorphic system were investigated both experimentally and theoretically. Theoretical studies such as lattice energy calculation, hydrogen‐bond strength estimation and Hirshfeld analysis were performed, providing further insight into the polymorphism/solvatomorphism of this system. Based on the analysis of the new form and the whole system, more solvates/cocrystals could be designed and unveiled in due time.