Barrier-free hydrogen bonds

Theoretical calculations of an [H3N H- NH3]+ system have shown that when the N - N distance is 2.75 A, the potential curve has two minima with a barrier of 10.9 klrnol with a decrease in the distance to ca 2.50 A, the barrier disappears. As seen in Table 5, the minimal N N distance for proton sponge cations is 2.54-2.55 A, i.e. none of the compounds has a symmetrical barrier-free H-bond. Indeed, in 80% of cases, the X-ray studies on salts of proton sponge 1 have revealed an asymmetric hydrogen bridge with the distances N—H and N - H in the ranges 0.84-1.27 A and 1.42-1.86 A, respectively. It is believed that such strong variations are due to the influence of the anion, either by an electric field effect or by structural changes in the crystal lattice. 

Most drug-like molecules dissolved in water form hydrogen bonds with the solvent. When such a molecule transfers from water into a phospholipid bilayer, the solute-water hydrogen bonds are broken (desolvation), as new solute-lipid H bonds form in the lipid phase. The free-energy difference between the two states of solvation has direct impact on the ability of the molecules to cross biological barriers. 

A.V. Degtyarev et al., 2,7-Disubstituted proton sponges as borderline systems for investigating barrier-free intramolecular hydrogen bonds. Protonated 2,7-bis(trimethylsilyl)-and 2,7-di (hydroxymethyl)-l,8-bis(dimethylamino)naphthalenes. Tetrahedron 64, 6209-6224 (2008)... 

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