No abstract

A strategy has been developed to achieve six-component molecular solids. The first part of the protocol involves the design and development of a family of stoichiometric quaternary cocrystals. It relies on the idea that when a molecule is in two distinct crystallographic environments in a lower-order cocrystal it becomes susceptible to substitution by a new molecule at the site where it is more weakly bound, if it is enthalpically advantageous to do so. Accordingly, a binary cocrystal acts as a stepping stone to a ternary, and so on. However, the subject system ran into a synthetic dead end at the level of quaternary cocrystals, in that no further crystallographic inequivalences could be found. This necessitated the development of the second part of the protocol, which exploits the shape-size similarities of 2-chloro-, 2-bromo-, and 2-methylresorcinols (CRES, BRES, and MRES respectively) and circumvents this synthetic dead end to achieve several five-and six-component solids, wherein the fifth and sixth components are incorporated in a solid solution fashion at the site of the fourth component.

Three ternary co-crystals of the title compound are reported. The design strategy hinges on the identification of a robust synthon with O− H•••N hydrogen bonds in a binary co-crystal. Construction of this module allows the tuning of π•••π stacking interactions and weak hydrogen bonds to incorporate the third component into the crystal structure. Screening of various co-formers showed that a delicate balance of electrostatics is required for stacking to favor the formation of ternaries. A C−H•••N hydrogen-bonded motif was also found to occur repetitively in the ternary co-crystals. The directional nature of weak hydrogen bonds allows them to be used effectively in this study.

Solid solutions (SS) of benzoic acid (BA) and 4-fluorobenzoic acid (4FBA) are monitored with respect to increasing fluorine content. All 10 SS studied take a crystal structure that is different from the crystal structures of either BA or 4FBA and retain structural uniformity over a wide range of composition. Adoption of a crystal structure different from either of the parent structure types is a unique observation in the context of SS. It implies the influence of directional interactions in the formation of the SS; this idea is strengthened by the observations made in this study. All the structural and interaction parameters monitored follow trends with respect to fluorine content. There is indication of the effect of C–H···F hydrogen bonds in the structures.

Co-crystal screening of the anti-HIV drug lamivudine was carried out with dicarboxylic acids as co-formers. Salts of cytosine, a molecule that incorporates critical structural features of lamivudine, with the same co-formers, were taken as model systems for IR spectroscopic studies of the synthons in the salts of lamivudine.