Revisiting HomochiralversusHeterochiral Interactions through a Long Detective Story of a Useful Azobis-Nitrile and Puzzling Racemate

Abstract

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.

Reinvigorating aza-Michael reactions under ionic liquid catalysis: a greener approach

“…To this end, we carried out an automated interaction site screening (aISS) 60 with the xTB program package 61,62 involving the pairs of ionic liquid-morpholine and ionic liquid-methyl acrylate, according to a similar methodology employed in previous work. 63 The final complexes denoted as Liq-M for morpholine and Liq-A for methyl acrylate were optimised at the above-mentioned DFT level of theory. Then, all electronic energies were refined with the same method and using the def2-TZVP basis set.…”