H-Bond Contribution to Octanol-Water Partition Coefficients of Polar Compounds

A quantitative description of the hydrogen bond contribution to logP is presented for carbonyl and hydroxyl compounds. A two parameter Eq. correlating the hydrophobicity with molecular volume and sum of free energy H‐bond acceptor ability is derived for carbonyl compounds. If compounds with hydroxyl groups are included also H‐bond donor abilities have to be considered. It can be concluded that hydrogen bonds play a very important role for the formation/presentation of hydrophobic properties of polar compounds. A quantitative description of the hydrogen bond contribution to logP values of such compounds is possible by means of free energy H‐bond acceptor and donor factor values only. Negative logP values result from the negative contribution of H‐bond acceptor ability.