Role of hydrophobic effects in mechanistic QSAR


To extend the successful application of Hammett equations, previously used to predict equilibrium and rates of physico-chemical reactions with electronic and steric parameters, to the realm of biology and biochemistry, a parameter that measures hydrophobicity is required. The partition coefficient of a solute between octanol and water, expressed in log terms to put it on the same free-energy basis as the classic Hammett parameters, has been shown to be widely applicable. It is directly involved in passive transport through membranes, in binding to proteins, and in specific binding at active sites in enzymes. Methods of calculating logP(octanol) that reflect the solvation forces involved, can be useful in elucidating unusual solute conformations that may be preferred in a non-polar environment.

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Leo, A.J., Hansch, C. Role of hydrophobic effects in mechanistic QSAR. Perspectives in Drug Discovery and Design 17, 1–25 (1999).

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  • log P
  • octanol
  • partition coefficient
  • QSAR