Prediction of Henry's law constant of benzene derivatives using quantum chemical continuum-solvation models

Semiempirical (SM2, SM5.4A, MST-AMI, COSMO-AM1) and ab inito (HF/PCM-vdW, M P2//PCM-vdW, COSMO-DFT) dielectric continuum-solvation models as well as th e surface-tension model SM5.0R are analyzed with respect to predicting Henr y's law constant at 25 degrees C using a compound set of benzene and 39 ben zene derivatives. Both hydrophilic and hydrophobic compounds are covered wi th a total variation in Henry's law constant of almost eight orders of magn itude corresponding to 44 kJ/mol, and the data set is selected such that th ere are cases where subtle changes in the molecular structure result in sub stantial changes of the free energy of solvation. The calculations with SM2 , COSMO-AM1, and COSMO-DFT include solution-phase geometry optimization, an d the ab initio results refer to polarized basis sets of double-zeta qualit y, with two gradient-corrected functionals (BPW and BLYP) being used for th e DFT-based models. The results show Considerable differences in performanc e between the different continuum-solvation models, and among the methods y ielding solvation free energies the systematic error ranges from -0.9 kJ/mo l (SM5.0R) to 12.1 kJ/mol (MP2//PCM-vdW). In particular, the nonelectrostat ic solvation energy contributions df SM2, SM5.4A, MST-AMI, and PCM-vdW do n ot correlate with each other, and with PCM-vdW omission of the nonelectrost atic component significantly improves the relative trend. The best statisti cs after scaling through linear regression are achieved with the electrosta tic component of MP2//PCM-vdW(r(adj)(2) = 0.94) and with COSMO-DFT (r(adj)( 2) = 0.93). The discussion includes detailed analyses of pecularities assoc iated with certain functional groups, deviations from the expected relation ship between dipole moment and solvation energy, and a simple approach to m odel dispersion interaction and cavitation energy by surface area terms tha t differentiate between individual atom types. (C) 2000 John Wiley & Sons,I nc.