Symmetry of hydrogen bonds in solution*

A classic question regarding hydrogen bonds (H-bonds) concerns their symmetry. Is the hydrogen centered or is it closer to one donor and jumping between them? These possibilities correspond to singleand double-well potentials, respectively. The NMR method of isotopic perturbation can answer this question. It is illustrated with 3-hydroxy-2-phenylpropenal and then applied to dicarboxylate monoanions. The 18O-induced 13C NMR splittings signify that their intramolecular H-bonds are asymmetric and that each species is a pair of tautomers, not a single symmetric structure, even though maleate and phthalate are symmetric in crystals. The asymmetry is seen across a wide range of solvents and a wide variety of monoanions, including 2,3-di-tert-butylsuccinate and zwitterionic phthalates. Asymmetry is also seen in monoprotonated 1,8-bis(dimethylamino)naphthalenediamines, N,N'-diaryl-6-aminofulvene-2-aldimines, and 6-hydroxy-2-formylfulvene. The asymmetry is attributed to the disorder of the local environment, establishing an equilibrium between solvatomers. The broader implications of these results regarding the role of solvation in breaking symmetry are discussed. It was prudent to confirm a secondary deuterium isotope effect (IE) on amine basicity by NMR titration of a mixture of PhCH2NH2 and PhCHDNH2. The IE is of stereoelectronic origin. It is proposed that symmetric H-bonds can be observed in crystals but not in solution because a disordered environment induces asymmetry, whereas a crystal can guarantee a symmetric environment. The implications for the controversial role of low-barrier H-bonds in enzyme-catalyzed reactions are discussed.