title: Synthesis, characterization, and molecular modeling of a pharmaceutical co-crystal: (2-chloro-4-nitrobenzoic acid):(nicotinamide).
abstract: The active pharmaceutical ingredient 2-chloro-4-nitrobenzoic acid (2c4n) is a potentially novel therapy for immunodeficiency diseases as an anti-viral and anti-cancer agent, and exists as a dimorph in the solid state. The Kofler hot stage contact method was employed to investigate the potential of preparing a co-crystal with nicotinamide (nic), a GRAS compound. The 1:1 co-crystal 1 was made using liquid-assisted grinding and solution crystallization experiments. The crystal structure determination of 1 reveals that the two molecules are associated via a carboxylic acid-pyridine hydrogen bond, while the nic forms a centrosymmetric R2(2)(8) dimer to ultimately form a ribbon architecture which is compared to other known co-crystals of nic. The melting point of the co-crystal is higher than the melting points of either of the pure components, indicating that the pharmaceutical co-crystal is thermally more stable than the pure pharmaceutical compound. The relative stability of the interactions in the co-crystal over the pure compounds is further supported by molecular modeling calculations.
authors.affiliation: Department of Chemistry, Ben-Gurion University of the Negev, PO Box 653, 84105 Beer-Sheva, Israel. andreas.lemmerer@gmail.com
authors.forename: Andreas
authors.initials: A
authors.lastname: Lemmerer
authors.forename: Catharine
authors.initials: C
authors.lastname: Esterhuysen
authors.forename: Joel
authors.initials: J
authors.lastname: Bernstein
mesh_terms: D002152:Calorimetry, Differential Scanning; D002723:Chlorobenzoates / Q000737:chemistry*; D003460:Crystallization / Q000379:methods*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D009536:Niacinamide / Q000737:chemistry*
chemical_list: C553671:2-chloro-4-nitrobenzoic acid; D002723:Chlorobenzoates; D009536:Niacinamide