This paper documents and reinvestigates the solid-state
and crystal
structures of 4,4′-azobis-4-cyanopentanoic acid (ACPA), a water-soluble
azobis-nitrile of immense utility as a radical initiator in living
polymerizations and a labile mechanophore that can be embedded within
long polymer chains to undergo selective scission under mechanical
activation. Surprisingly, for such applications, both the commercially
available reagent and their derivatives are used as “single
initiators” when this azonitrile is actually a mixture of stereoisomers.
Although the racemate and meso compounds were identified
more than half a century ago and their enantiomers were separated
by classical resolution, there have been confusing narratives dealing
with their characterization, the existence of a conglomeratic phase,
and fractional crystallization. Our results report on the X-ray crystal
structures of all stereoisomers for the first time, along with further
details on enantiodiscrimination and the always intriguing arguments
accounting for the stability of homochiral versus heterochiral crystal aggregates. To this end, metadynamic (MTD)
simulations on stereoisomer molecular aggregates were performed to
capture the incipient nucleation events at the picosecond time scale.
This analysis sheds light on the driving homochiral aggregation of
ACPA enantiomers.