title: Identification of New Cocrystal Systems with Stoichiometric Diversity of Salicylic Acid Using Thermal Methods.
abstract: OBJECTIVE
  The purpose of this work was to develop thermal methods to identify cocrystal systems with stoichiometric diversity.
  
  
  METHODS
  Differential scanning calorimetry (DSC) and hot stage microscopy (HSM) have been applied to study the stoichiometric diversity phenomenon on cocrystal systems of the model compound salicylic acid (SA) with different coformers (CCFs). The DSC method was particularly useful in the identification of cocrystal re-crystallization, especially to improve the temperature resolution using a slower heating rate. HSM was implemented as a complementary protocol to confirm the DSC results. The crystal structures were elucidated by single-crystal X-ray diffraction (SXRD).
  
  
  RESULTS
  Two new cocrystal systems consisting of salicylic acid-benzamide (SA-BZD, 1:1, 1:2) and salicylic acid-isonicotinamide (SA-ISN, 1:1, 2:1) have been identified in the present work. The chemical structures of the newly discovered cocrystals SA-BZD (1:2) and SA-ISN (2:1) have been elucidated using X-ray single crystal and powder diffraction methods.
  
  
  CONCLUSIONS
  The developed thermal methods could rapidly identify cocrystal systems with stoichiometric diversity, with the potential to discover new pharmaceutical cocrystals in the future.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, SAR, China.
authors.forename: Zhengzheng
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, SAR, China.
authors.forename: Hok Man
authors.initials: HM
authors.lastname: Chan
authors.affiliation: Department of Chemistry, The Hong Kong University of Science & Technology, Hong Kong, SAR,, China.
authors.forename: Herman H-Y
authors.initials: HH
authors.lastname: Sung
authors.affiliation: School of Health Sciences, Macao Polytechnic Institute, Macao, SAR, China. henrytong@ipm.edu.mo.
authors.forename: Henry H Y
authors.initials: HH
authors.lastname: Tong
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, SAR, China. yzheng@umac.mo.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry*; D001549:Benzamides / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D009536:Niacinamide / Q000737:chemistry*; D033362:Powder Diffraction; D020156:Salicylic Acid / Q000737:chemistry*; D013696:Temperature
chemical_list: D000890:Anti-Infective Agents; D001549:Benzamides; D009536:Niacinamide; C027681:isonicotinamide; C037689:benzamide; D020156:Salicylic Acid
keywords: cocrystal; differential scanning calorimetry (DSC); hot stage microscopy (HSM); salicylic acid (SA); stoichiometry; thermal