Current Computer-Aided Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811


Hydrogen Bonding Contribution to Lipophilicity Parameters. Hydrogen Acceptor and Hydrogen Acceptor-Donor Parameters for Substituents Bonded to sp2-Hybridized Carbon Atoms

Author(s): Marvin Charton.


Hydrogen bonding parameters for QSAR are reviewed. Forty five hydrogen bonding parameters for hydrogen acceptor groups and fifteen for hydrogen acceptor and donor groups for substituents bonded to sp2 hybridized carbon atoms (ήXPh) were derived from1-octanol/water partition coefficients by the method previously used for substituents bonded to sp3 hybridized carbon atoms (ήXAk). The parameters derived from log PO/W values for substituted benzenes are applicable to any data set in which substituents are bonded to sp2 hybridized carbon atoms. In aqueous solutions a leveling effect occurs with regard to groups that are hydrogen donors. Thus, groups that are both hydrogen donors and acceptors in aqueous solutions function only as hydrogen acceptors. Colinearity exists between bond moment and hydrogen bonding parameters which may mask the dependence of log PO/W on the former. Partition coefficients of substituted cyclopropanes are probably a function of ήXPh rather than of ήXAk. A study of a data set of 1-substituted naphthalenes showed no significant interaction between a substituent in position 1 and the carbon atom in position 8. Partition coefficients are a function of polarizability, hydrogen bonding, and in some cases, bond moment; the first two effects are dominant. For a data set XG where G is the skeletal group to which the substituent X is bonded the polarizability of both X and G is important.

Keywords: Hydrogen bonding, hydrogen acceptor groups, hydrogen donor groups, hydrogen acceptor and donor groups, partition coefficients, substituted cyclopropanes, polarizability, bond moments

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Article Details

Year: 2006
Page: [353 - 368]
Pages: 16
DOI: 10.2174/157340906778992337
Price: $58