Pseudopolymorphism Driven by Stoichiometry and Hydrated/Anhydrous Reagents: The Riveting Case of Methyl Gallate·l-Proline

Among GRAS molecules, α-amino acids have been extensively used to produce molecular salts and cocrystals of APIs thanks their nontoxicity, ready availability, cheapness, zwitterionic nature. Here we report on the use both anhydrous hydrated l-proline (Pro Pro·H2O, respectively) with methyl gallate (MG) selectively obtain by mechanochemical methods cocrystals: MG·Pro2 MG2·Pro2·H2O, respectively. The two new forms were characterized means single-crystal powder X-ray diffraction (SCXRD PXRD), solid-state nuclear magnetic resonance (SSNMR), DSC, TGA. Interestingly, choice starting material together stoichiometry drives formation cocrystal toward either or hydrate form: form could be obtained only from Pro, whereas Pro·H2O Pro matching correct stoichiometry. An energy framework analysis allowed us rationalize this peculiar water uptake behavior in terms relative interaction strengths proline–proline, proline–water, proline–methyl pairs packing features.