When Counting Electrons Matter: Tuning Noncovalent Interactions with Aromaticity

Aromaticity and hydrogen bonding are traditionally considered to be largely separate ideas in chemistry. We find however, that just as a change in aromaticity can enhance chemical reactivity (e.g., consider the effect of an aromatic transition state on a cycloaddition reaction)—a change in aromaticity can perturb the strengths of hydrogen bonding interactions (and even more exotic types of noncovalent interactions). Hydrogen-bonding interactions that polarize π-electrons to increase cyclic [4n+2] π-electron delocalizations (i.e., enhance aromaticity) in heterocycles are stronger than expected, while those that decrease cyclic [4n+2] π-electron delocalization (i.e., reduce aromaticity) are weakened. Following Baird’s Rule for excited-state aromaticity (a reverse of the Hückel rule), hydrogen bonding interactions at specific ππ* excited states display the opposite trend. Anion-π interactions—even without a π-acidic ring—can be especially favorable when they achieve 3D “six-interstitial electron” aromaticity. I will talk about the interpretive merit, predictive power, and probable impacts of these special connections for applications in organic and supramolecular chemistry (e.g., in enzyme catalysis, self-assembly, host-guest recognition)