First Comparative Study of the Three Polymorphs of Bis(isonicotinamide) Citric Acid Cocrystals and the Concomitant Salt 4-Carbamoylpyridinium Citrate Isonicotinamide

This contribution presents a previously unreported example and comparative study of a binary crystalline adduct that exhibits concomitant salt and cocrystal forms. Specifically, three new polymorphs ( α, β, γ ) of a novel 2:1 cocrystal of bis(isonicotinamide) citric acid are reported, and the route to isolating each polymorph from aqueous solution is presented and the crystal chemistry of the system is characterized. In addition, the metastable 2:1 salt (ionic adduct) isolated as a transient (overlapping) phase under crystallization conditions identical to the polymorphs is also presented. As far as the authors can ascertain, this may be the first reported example of a salt–cocrystal–polymorphic concomitant system. A comparative study of the solid form landscape is presented, wherein mapping reveals the unique structural complexity of this multiple form salt–cocrystal concomitant system. The α and β forms are structurally very similar, where comparisons of packing behavior are shown to only be different outside the glide plane. The γ form is very different in structure, where supramolecular chirality is present. In addition, further characterization of the isolated solid-state forms includes thermal, spectroscopic, and computational analysis, all of which are employed to further verify the solid form landscape of the isonicotinamide–citric acid adduct and were found to have an order of stability of β, α, γ, salt, the salt being the metastable form.