Quantifying hydrogen bonding in QSAR and molecular modeling

Abstract

Quantitative descriptions of hydrogen bonding for use in QSAR and molecular modeling by means of H-bond descriptors have been analyzed in detail in this paper. Ten new H-bond surface and enthalpy integral descriptors were proposed. The usefulness of these new descriptors, as well as previously developed descriptors was verified using a set of 154 drugs for which data for intestinal absorption in humans were available. The results showed that descriptors such as the number of H-bond acceptor and donor atoms and polar surface area (PSA) did not sufficiently describe the actual H-bonding ability of atoms in molecules. Thus, to enable successful modeling it was necessary to introduce descriptors directly related to the experimental thermodynamics of hydrogen bonding.

Keywords:

• H-bond descriptors
• Human intestinal absorption
• H-bond surface area
• Molecular descriptors

Acknowledgements

The authors thank Dr J.W. McFarland for his valuable comments during the preparation of this manuscript.