Directing the Solid-State Organization of Racemates via Structural Mutation and Solution-State Assembly Processes

Chirality
plays a central role in biomolecular recognition and
pharmacological activity of drugs and can even lead to new functions
such as spin filters. Although there have been significant advances
in understanding and controlling the helical organization of enantiopure
synthetic molecular systems, rationally dictating the assembly of
mixtures of enantiomer (including racemates) is nontrivial. Here we
demonstrate that a subtle change in molecular structure coupled with
the understanding of assembly processes of enantiomers and racemates,
in both dilute solution and concentrated gels, acts as a stepping
stone to rationally control the organization in the solid-state. We
have studied trans-1,2-disubstituted cyclohexanes
as model systems with carboxamide, thioamide, and their combination
as functional groups. On comparing the gelation propensity of individual
enantiomers and racemates, we find that racemates of carboxamide,
thioamide, and their combination adopt self-sorting, coassembly, and
mixed organization, respectively. Remarkably, these modes of assembly
of racemates were also retained in solid-state. These results point
out that studying the solution-phase assembly is a key link for connecting
molecular structure with the assembly in the solid-state, even for
racemates.