First and Second Dissociation Enthalpies in Bi-Component Crystals Consisting of Maleic Acid and L-Phenylalanine

The energetics of the stepwise dissociation of a A:B-2 bi-component crystal, according to A:B-2(cr) -> A:B(cr) + B(cr) and A:B(cr) -> A(cr) + B(cr), was investigated using MA:Phe(2) and MA:Phe (MA = maleic acid; Phe = L-phenylalanine) as model systems. The enthalpy changes associated with these sequential processes and with the overall dissociation reaction A:B-2(cr) -> A(cr) + 2B(cr) were determined by solution calorimetry. It was found that they are all positive, indicating that there is a lattice enthalpy gain when MA:Phe(2) is formed, either from the individual precursors or by adding Phe to MA:Phe. Single-crystal X-ray diffraction (SCXRD) analysis showed that MA:Phe(2) is best described as a protic salt containing a maleate anion (MA(-)) and two non-equivalent L-phenylalanine units, both linked to MA(-) by NH center dot center dot center dot O hydrogen bonds (H-bond): one of these units is protonated (HPhe(+)) and the other zwitterionic (Phe(+/-)). Only MA(-) and HPhe(+) molecules are present in the MA:Phe lattice. In this case, however, NH center dot center dot center dot O and OH center dot center dot center dot O H-bonds are formed between each MA(-) unit and two HPhe(+) molecules. Despite these structural differences, the enthalpy cost for the removal of the zwitterionic Phe(+/-) unit from the MA:Phe(2) lattice to yield MA:Phe is only 0.9 +/- 0.4 kJ mol(-1) higher than that for the dissociation of MA:Phe, which requires a proton transfer from HPhe(+) to MA(-) and the rearrangement of L-phenylalanine to the zwitterionic, Phe(+/-), form. Finally, a comparison of the dissociation energetics and structures of MA:Phe and of the previously reported glycine maleate (MA:Gly) analogue indicated that parameters, such as the packing coefficient, density, hydrogen bonds formed, or fusion temperature, are not necessarily good descriptors of dissociation enthalpy or lattice enthalpy trends when bi-component crystals with different molecular composition are being compared, even if the stoichiometry is the same.

Automated summary

The study investigated the energetics of the stepwise dissociation of a A:B-2 bi-component crystal and found that structural differences between maleic acid and L-phenylalanine have minimal impact on the enthalpy cost for dissociation. Additionally, comparing bi-component crystals with different molecular compositions may not be accurately described by lattice enthalpy trends.