Halogen bonding, arguably the most prominent σ-hole interaction, has become an indispensable tool for chemists, used in a wide variety of application ranging from design and synthesis of liquid crystalline, phosphorescent and non-linear optical materials, to resolution of racemic mixtures, and pharmaceutical property modulation through co-crystal formation.  These applications are realized as a direct result of the high directionality and tunability of these σ-hole interactions, where the magnitude of the σ-hole potentials are used as a yardstick to measure the strength of its halogen bond donor ability. A very strong interaction results in synthon robustness which is significant when it comes to molecular recognition, structural prediction, self-assembly and design strategy. A double activation strategy has been previously demonstrated  by Aakeröy et al. to produce effective and powerful halogen bond donors with very high σ-hole potentials. In this work, we attempt to answer the question, can the boundaries of activation be pushed even further, by a triply activated halogen bond donor? Here we present the first such examples through a library of triply activated 3-iodo-1-phenylprop-2-yn-1-ones differently substituted with -F, -C≡N and -NO<sub>2</sub> groups which demonstrate the highest known σ-hole potentials to date. The targets possess multiple possible acceptor sites within its structure, but which among them will the halogen-bond donor prefer to bind to? We attempt to predict this theoretically by computing the interaction energies for these different interactions and co-relate these predictions with that experimentally observed from their crystal structures. We also compute interaction energies between synthesized targets and ammonia as a model acceptor to predict the most stable interaction from within this series.

A group of world class halogen-bond donors: A structural and theoretical analysis of “triply activated” 3-iodo-1-phenylprop-2-yn-1-ones with exceptional σ-hole potentials

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.