Revisiting Homochiral <i>versus</i> Heterochiral Interactions through a Long Detective Story of a Useful Azobis-Nitrile and Puzzling Racemate

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