Collection of Czechoslovak Chemical Communications - digital archive 

Abstract

In our analysis of the composition of lipophilicity parameters by the intermolecular force (IMF) model we have made use of n_H, the number of OH and/or NH bonds, as a measure of the hydrogen donor capacity of a substituent; and n_n, the number of lone pairs on O and/or N atoms in the substituent, as a measure of the hydrogen acceptor capacity of the substituent. The basis of this method is the reasonable assumption that in 55.6 molar water hydrogen bonding is maximized. The method does not account however for differences in the energy of different types of hydrogen bonds, but further assumes that these differences are to a first approximation negligible. In order to improve the model we have defined a scale of group hydrogen bonding acceptor parameters, η_XHA, and overall hydrogen bond parameters η_XHAD from the water/1-octanol partition coefficients of AkX where Ak is alkyl. These parameters should account for both the extent of hydrogen bonding in water and for the difference in hydrogen bond energies of the various types of hydrogen bonds encountered. Correlations of log P values for Ph(CH₂)_nX, X¹(CH₂)X², and substituted amino acids Xaa with the IMF equation using the η_XHA and η_XHAD parameters demonstrated their use. Correlation of log P values for PhX suggested that for many groups separate sets of η_XHA and η_XHAD values are required when they are bonded to sp² hybridized carbon rather than sp³ hybridized carbon.

Keywords: Hydrogen bonds; Lipophilicity; Intermolecular force model; Partition coefficient; Substituent effects.

References: 24 live references.