Kinetic modeling using nonlinear differential equations is proposed to analyze the spontaneous generation of enantiomeric excess in the autocatalytic addition of diisopropylzinc to prochiral pyrimidine carbaldehydes (Soai reaction). Our approach reproduces experimentally observed giant chiral amplification from an initial enantiomeric excess of 60%, high sensitivity and positive response to the presence of minute amounts of chiral initiator at concentrations <10^–14M, and spontaneous absolute asymmetric synthesis from achiral starting conditions. From our numerical simulations using kinetic schemes derived from the Frank model, including stereospecific autocatalysis and mutual inhibition, we have shown that it is possible to reproduce the mirror-symmetry-breaking behavior of the Soai reaction under batch conditions leading to a bimodal enantiomeric product distribution. Mirror-symmetry breaking was found to be resistant to a loss of stereoselectivity up to 30%. While the mutual inhibition between enantiomers seems to originate from the presence of dimerization equilibria, the exact nature of the autocatalytic stereoselective process still remains to be revealed. From the kinetic viewpoint, simple autocatalysis involving monomers as the catalytic species is consistent with all reported experimental effects of the Soai reaction.

Combination of nitazoxanide (NTZ) with a total of 32 cocrystal formers gave cocrystals with succinic acid (NTZ-SUC, 2:1) and glutaric acid (NTZ-GLU, 1:1). Additionally, 2,5-dihydroxybenzoic acid provided a cocrystal solvate with acetonitrile (NTZ-25DHBA-CH₃CN, 1:1:1). All solid phases were characterized by X-ray powder diffraction analysis, IR spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and single-crystal X-ray diffraction analysis. Single-crystal X-ray crystallography revealed that NTZ and the carboxylic acid cocrystal formers were linked in all three cocrystals through the same supramolecular heterodimeric synthon, C(N)NH···HOOC. Despite having different stoichiometries, the crystal structures of NTZ-SUC and NTZ-GLU showed similarities in the supramolecular organization, both containing two-dimensional layers formed by NTZ molecules, which were further interconnected by single (NTZ-SUC) and homodimeric entities (NTZ-GLU) of the cocrystal former. Basic physical stability tests showed that cocrystals NTZ-SUC and NTZ-GLU are stable at least for one month under standardized temperature/relative humidity stress conditions but decompose within 1 h into the corresponding physical phase mixtures, when exposed to aqueous solutions simulating physiological gastrointestinal conditions. Measurement of the dissolution rates gave small increases of the intrinsic dissolution rate constants when compared with NTZ. Pressure stability tests showed that the cocrystals support higher pressures (at least up to 60 kg/cm²) than NTZ.