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Solvation in octanol: parametrization of the continuum MST model
Author(s) -
Curutchet Carles,
Orozco Modesto,
Luque F. Javier
Publication year - 2001
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.1076
Subject(s) - solvation , parametrization (atmospheric modeling) , partition coefficient , chemistry , octanol , monte carlo method , thermodynamics , root mean square , absolute deviation , water model , partition (number theory) , computational chemistry , solvent , molecular dynamics , physics , mathematics , chromatography , organic chemistry , quantum mechanics , combinatorics , radiative transfer , statistics
This study reports the parametrization of the HF/6‐31G(d) version of the MST continuum model for n ‐octanol. Following our previous studies related to the MST parametrization for water, chloroform, and carbon tetrachloride, a detailed exploration of the definition of the solute/solvent interface has been performed. To this end, we have exploited the results obtained from free energy calculations coupled to Monte Carlo simulations, and those derived from the QM/MM analysis of solvent‐induced dipoles for selected solutes. The atomic hardness parameters have been determined by fitting to the experimental free energies of solvation in octanol. The final MST model is able to reproduce the experimental free energy of solvation for 62 compounds and the octanol/water partition coefficient (log P ow ) for 75 compounds with a root‐mean‐square deviation of 0.6 kcal/mol and 0.4 (in units of log P ), respectively. The model has been further verified by calculating the octanol/water partition coefficient for a set of 27 drugs, which were not considered in the parametrization set. A good agreement is found between predicted and experimental values of log P o/w , as noted in a root‐mean‐square deviation of 0.75 units of log P . © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1180–1193, 2001