Acid···Amide Supramolecular Synthon in Cocrystals: From Spectroscopic Detection to Property Engineering

The acid···amide dimer
heterosynthon in cocrystals
of aromatic acids and primary amides is identified by marker peaks
in the IR spectra that are characteristic of individual N–H···O
and O–H···O interactions and also of the extended
synthon. The O–H···O hydrogen bond is crucial
to heterodimer formation in contrast to the N–H···O
bond. A combinatorial study, tuning the chemical nature of acid and
amide functionalities, leads to 22 cocrystals out of 36 crystallization
attempts. Four quadrants I–IV are defined based on acidity
and basicity of the acid and amide components. The strong acid–strong
base combination in quadrant I favors the planar acid···amide
heterodimer in its eight cocrystals. Quadrant IV with its weak acid–weak
base combination is the least favored for the planar heterosynthon
and synthon diversity is observed in the eight cocrystals obtained.
The strong–weak and weak–strong combinations in quadrants
II and III are expectedly ambivalent. This exercise highlights the
effect of molecular features on supramolecular behavior. Quadrant
I crystals, with their propensity for the planar acid···amide
heterodimer are suitable for the engineering of crystals that can
be sheared. This quadrant favors the formation of elastic crystals
too. The overall result is that 57% (4 in 7) of all crystals in this
quadrant are deformable, compared with 14% (1 in 7) in the three other
quadrants. This work is a complete crystal engineering exercise from
synthon identification to a particular desired crystal packing to
property selection. One can virtually anticipate the mechanical property
of a putative acid···amide cocrystal from a knowledge
of just the molecular structures of the constituent acid and amide
molecules.