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

• Published in: European journal of medicinal chemistry 1998-10, Vol.33 (10), p.799-807
• Main Authors: Raevsky, Oleg A., Schaper, Klaus-Jürgen
• Format: Article
• Language: English
• Subjects: absorption; descriptors; H-bond acceptor; H-bond donor; membrane; permeability; QSAR
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/S0223-5234(99)80031-2

The H-bond donor and acceptor descriptors Σ C d and Σ C a, which are estimated directly from thermodynamic data ofhydrogen 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 Σ C d and Σ C a, often only the more significant of them leads to a significant regression coefficient in multiple linear regression equations. In comparison with Σ C d and/or Σ C a less significant correlations are obtained with the experimental parameter Δlog P (the difference between the octanol/water partition coefficient log P Oct and log P 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.