A test of various computational solvation models on a set of “difficult” organic compounds

Abstract

Various dielectric continuum models in Gaussian 03, based on the SCRF approach, PCM, CPCM, DPCM, IEFPCM, IPCM, and SCIPCM, have been tested on a set of 54 highly polar, generally polyfunctional compounds for which experimental solvation energies are available. These compounds span a range of 13 kcal/mol in ΔGt. The root-mean-square (RMS) errors for the full set of compounds range from 2.48 for DPCM to 1.77 for IPCM. For each method, classes of compounds which were not handled well could be identified. If these classes of compounds were omitted, the performance improved, and ranged from 1.58 (PCM, 39 compounds) to 1.02 (IPCM, 42 compounds). Models in the PCM family (PCM, CPCM, DPCM, and IEFPCM) with the recommended UAHF or UAKS sets of radii rely on a highly parameterized definition of the solvent cavity. Where this parameterization was inadequate, the calculated solvation energies were less reliable. This has been demonstrated by devising a new parameterization for PCM and halogen compounds, which markedly improves performance for polyhalogen compounds. The effective radius for the portion of the cavity centered on a halogen atom was assumed to be linear in the electron-withdrawing or -donating properties of the rest of the molecule as measured by Hammett σ (for halogens on aromatic rings) or Taft σ* (for halogens on aliphatic carbons). This new parameterization for PCM was tested on a set of 45 aliphatic and 22 aromatic polyhalogen compounds and shown to do well. IPCM, which was already the best of the methods in Gaussian, can be considerably improved by a parameterization to allow for cavitation, dispersion, and hydrogen bonding. A large set of compounds was used for the parameterization to have multiple examples for each parameter and as far as possible to have molecules with multiple instances of each structural feature. In the end, 15 parameters were found to be defined by the data for 241 compounds. With this parameter set, the RMS error for the set used for fitting was 0.81 kcal/mol, and the RMS error for the original set of 54 compounds was 0.85. With this new parameterization, IPCM is clearly the best of the methods available in Gaussian 03.