Quantitative estimation of hydrogen bond contribution to permeability and absorption processes of some chemicals and drugs

The H-bond donor and acceptor descriptors Sigma C-d and Sigma C-a, which are estimated directly from thermodynamic data of hydrogen bonding, were successfully used for the correlation with permeability and absorption data for some chemicals and drugs. The evaluation of different types of permeability test systems and of different classes of compounds showed that in addition to steric bulk effects both the H-bond donor and acceptor strength play an important role in explaining differences in permeability and absorption of neutral chemical compounds and drugs. However, because of the frequently observed intercorrelation between Sigma C-d and Sigma C-a, often only the more significant of them leads to a significant regression coefficient in multiple linear regression equations. In comparison with Sigma C-d and/or Sigma C-a less significant correlations are obtained with the experimental parameter Delta logP (the difference between the octanol/water partition coefficient logP(Oct) and logP for the system alkane or cyclohexane/water) which has to be considered as a composed descriptor containing H-bond donor as well as H-bond acceptor effects. (C) Elsevier, Paris.