Quantitative structure-property relationships for predicting Henry's law constant from molecular structure

Environ Toxicol Chem. 2003 Aug;22(8):1755-70. doi: 10.1897/01-605.

Abstract

Various models are available for the prediction of Henry's law constant (H) or the air-water partition coefficient (Kaw), its dimensionless counterpart. Incremental methods are based on structural features such as atom types, bond types, and local structural environments; other regression models employ physicochemical properties, structural descriptors such as connectivity indices, and descriptors reflecting the electronic structure. There are also methods to calculate H from the ratio of vapor pressure (p(v)) and water solubility (S(w)) that in turn can be estimated from molecular structure, and quantum chemical continuum-solvation models to predict H via the solvation-free energy (deltaG(s)). This review is confined to methods that calculate H from molecular structure without experimental information and covers more than 40 methods published in the last 26 years. For a subset of eight incremental methods and four continuum-solvation models, a comparative analysis of their prediction performance is made using a test set of 700 compounds that includes a significant number of more complex and drug-like chemical structures. The results reveal substantial differences in the application range as well as in the prediction capability, a general decrease in prediction performance with decreasing H, and surprisingly large individual prediction errors, which are particularly striking for some quantum chemical schemes. The overall best-performing method appears to be the bond contribution method as implemented in the HENRYWIN software package, yielding a predictive squared correlation coefficient (q2) of 0.87 and a standard error of 1.03 log units for the test set.

Publication types

  • Review

MeSH terms

  • Chemical Phenomena
  • Chemistry, Physical*
  • Forecasting
  • Gases
  • Models, Theoretical*
  • Molecular Structure
  • Pressure
  • Quantitative Structure-Activity Relationship*
  • Software
  • Solubility
  • Solvents
  • Temperature
  • Volatilization

Substances

  • Gases
  • Solvents