Hydrogen bonding, factors affecting strength

Our detailed knowledge of the mechanism of proton transfer from intramolecularly hydrogen-bonded acids and our understanding of the factors that affect the strength of intramolecular hydrogen bonds have now reached a stage when correlations of the proton-transfer behaviour with the nature of the hydrogen bond will soon be possible. 

Poorly absorbed compounds have been identified as those with a PSA >140 A2. Considering more compounds, considerably more scatter was found around the sigmoidal curve observed for a smaller set of compounds [71]. This is partly due to the fact that many compounds not only show simple passive diffusion but are also affected by active carriers, efflux mechanisms involving P-glycoprotein (P-gp) and other transporter proteins, and gut wall metabolism. These factors also contribute to the considerable interindividual variability of human oral absorption data. A further refinement in the PSA approach is expected to come from taking into account the strength of the hydrogen bonds, which in principle already is the basis of the HYBOT approach [60-62],... 

The influence of solvent in hydrogen bonding has been studied by Lorenzi, In these studies it was shown that a small cyclic peptide does not dimerize in chloroform. In a less competitive solvent like carbon tetrachloride, however, a dimerization constant of 80 is observed [27], The solvation of the binding site is a critical factor affecting the strength of binding, Wilcox has studied... 

---