New hydrate cocrystal of L-proline with 4-acetylphenylboronic acid obtained via mechanochemistry and solvent evaporation: An experimental and theoretical study

In this work, we present the formation of a new multi-component molecular complex by targeting the boronic acid moiety (-B(OH)₂) of 4-acetylphenylboronic acid with the carboxylate group (-COO^-) of L-proline using two different techniques: mechanochemistry and solvent evaporation. The experiments produced efficiently a new cocrystal named L-PRO4APBA. It was characterised to study its structural properties by X-ray powder diffraction (XRPD), infrared spectroscopy (FTIR), single-crystal X-ray diffraction (SCXRD), and quantum chemical methods based on QTAIM. Also, its thermal behaviour was analysed using a simultaneous DSC/TGA experiment. The results showed that L-PRO4APBA comprises discrete molecular units held together mainly by O–H⋯O and N–H⋯O hydrogen bonds. However, C–H⋯O, C–H⋯π, and other non-conventional interactions gave further stabilisation. Moreover, SCXRD showed that the asymmetric unit contains five independent molecules: two of L-proline (PRO1 and PRO2), two of 4-acetylphenylboronic acid (4APBA1 and 4APBA2) and one of water. PRO1 and PRO2 adopted different conformations with their carboxylate groups in equatorial and axial positions, respectively. This feature produced two independent helical chains running along the 2₁ screw axis in which 4APBA1 and 4APBA2 bound through the expected -B(OH)₂···⁻OOC- heterosynthon. Surprisingly, the presence of water molecules in the lattice did not disrupt the formation of this motif. However, water molecules played an essential role for the stabilisation of the 3D structure. These findings would set up the structural basis to continue exploring the formation of new cocrystals by combining L-proline with boronic acids.