Subject: calculation of pka valuse by ab initio methods

From: DE BRUIN theodorus <theodorus.DE-BRUIN_at_ifp.fr>
Date: Wed, 11 Feb 2004 10:30:11 +0100

Dear CCLers,
 
According to you, what is the best method to calculate absolute pKa values,
i.e. without first deriving some linear semi-empirical equation for a
training set, but to calculate pKa directly from the Delta G of the
dissociation reaction. I would like to calculate pKa values for some medium
sized molecules, NOT just in water, but in mixtures of water with alcohols
for which experimental data are very sparse.

I am aware that the calculated solvation energy for charged species can
contain relatively big errors, affecting Delta G and finally resulting in
errors of several units in the pKa value. 
According to some people, this problem can partially be overcome by applying
continuum models in which explicitly some solvent molecules are taken up. 
Is DFT accurate enough, which continuum model is best, etc...
 
I'll summarize the results.
 
Thanks in advance,
Theo de BRUIN