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The two-component crystals formed from pyridine or 4-dimethylaminopyridine with maleic, fumaric, phthalic, isophthalic, or terephthalic acids were characterized by X-ray diffraction. The two-component solid forms involving pyridine included both salts and cocrystals, while 4-dimethylaminopyridine crystallized exclusively as a salt, in agreement with the differences in the pKavalues. Five previously unknown salt solid forms of 4-dimethylaminopyridine and the crystal structure of a pyridine fumaric acid (2:1) cocrystal are reported. An in-situ base catalyzed isomerization of maleic acid was observed in cocrystallization experiments involving pyridine. The salts formed between 4-dimethylaminopyridine and fumaric acid included one or two fumaric acid molecules within the crystal lattice. Thus, the reported grid of crystal forms demonstrates the limitations of empirical rules for predicting the stoichiometry and covalent bonding of the acidic proton within salts and cocrystals. Many of the crystal structures displayed either the neutral or the ionic form of the carboxylic acid−pyridine heterosynthon, and the similarity in crystal structures between the neutral and the ionized molecules makes the visual distinction between a salt or cocrystal dependent on the experimental location of the acidic proton. Computational modelling experiments, by relocating the acid protons in the salts to produce cocrystals and vice versa, show that the crystal structure can be better modelled when the crystallographic designation of salt or cocrystal is used. Periodic electronic structure calculations also show that there is generally a significant energy penalty to relocate the acidic proton, which is considerably reduced when experiments indicate the presence of disorder in the acidic proton position. [ABSTRACT FROM AUTHOR]

A combined computational and experimental polymorph search was undertaken to establish the crystal forms of 7-fluoroisatin, a simple molecule with no reported crystal structures, to evaluate the value of crystal structure prediction studies as an aid to solid form discovery. Three polymorphs were found in a manual crystallisation screen, as well as two solvates. Form I (P21/c, Z′ = 1), found from the majority of solvent evaporation experiments, corresponded to the most stable form in the computational search of Z′ = 1 structures. Form III (P21/a, Z′ = 2) is probably a metastable form, which was only found concomitantly with form I, and has the same dimeric R22(8) hydrogen bonding motif as form I and the majority of the computed low energy structures. However, the most thermodynamically stable polymorph, form II (P1̄, Z′ = 2), has an expanded four molecule R44(18) hydrogen bonding motif, which could not have been found within the routine computational study. The computed relative energies of the three forms are not in accord with experimental results. Thus, the experimental finding of three crystalline polymorphs of 7-fluoroisatin illustrates the many challenges for computational screening to be a tool for the experimental crystal engineer, in contrast to the results for an analogous investigation of 5-fluoroisatin. [ABSTRACT FROM AUTHOR]