Role of Functionalities in Structural Analogues Urocanic Acid and l-Histidine, toward the Formation of Anhydrous and Hydrated Molecular Salts

Abstract

Cocrystallization of structural analogues urocanic acid and l-histidine with mono-, di-, and trisubstituted hydroxy benzoic acids has been carried out to gain insights into the formation of anhydrous and hydrated molecular salts. Urocanic acid generated anhydrous molecular salts with 2-hydroxy, 3,5-dihydroxy, and 2,4,6-trihydroxybenzoic acids, whereas 2,3-dihydroxy, 3,4-dihydroxy, and 3,4,5-trihydroxybenzoic acids resulted in hydrated salts. Cocrystallization experiments of anhydrous l-histidine with 2,3-dihydroxy, 3,4-dihydroxy, 3,5-dihydroxy, 3,4,5-trihydroxy, and 2,4,6-trihydroxybenzoic acids resulted in hydrated molecular salts. However, l-histidine 2-hydroxybenzoic acid formed an anhydrous molecular salt. In this context, the hitherto elusive structure of native urocanic acid (anhydrous form) has been determined. The rationale for the formation of hydrated and anhydrous salts is evaluated in terms of the hydroxyl substituents on benzoic acids and the presence of additional amino group in l-histidine. Differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA) proved the presence or absence of hydration, whereas Fourier-transform infrared (FT-IR) experiments confirmed proton transfer suggesting the formation of molecular salts for those combinations that did not produce good quality single crystals for diffraction.