AMHB: Anti(aromaticity) Modulated Hydrogen Bonding

Aromaticity and H-bonding are common features of many heterocycles from DNA basepairs to ligands binding proteins. Despite being known as separate bonding concepts for morethan a century, their interplay has been underappreciated. An in-silico survey on a wide rangeof aromatic and antiaromatic heterocycles capable of H-bonding shows a uniform pattern fortheir interplay: H-bonding interactions that enhance aromaticity or relieve antiaromaticity arefortified, whereas those that intensify antiaromaticity or disrupt aromaticity are weakened,relative to analogs lacking full π-circuits . Attribution of these energetic to (anti)aromaticityis supported by the calculated changes of dissected nucleus-independent chemical shift(NICS(1)zz: a computable index of (anti)aromaticity). Furthermore, experimental measurementsshow that the effect remains significant in solution phase, and provide energetic, magnetic,and geometric evidence for AMHB.