Subject: summary : calculation of pka valuse by ab initio methods

From: DE BRUIN theodorus <theodorus.DE-BRUIN!at!ifp.fr>
Date: Tue, 2 Mar 2004 14:36:32 +0100

Dear CCLers,

Recently, I've asked a question about calculation pKa values using ab initio
methods (see below). For the moment I've received 3 replies:

COSMO-RS is the only code I know that will deal with real solvents, beyond
the zeroth order dielectric continuum...
John McKelvey

I am very skeptical of the ability of any current ab initio method to
accurately calculate pKa's.  Consider acetic acid.  Its pKa is dominated by
solvent effects and is largely determined by deltas and not deltaH.
Wayne E. Steinmetz

we recently published a calculation scheme for pKa (pKb will follow soon,
prel. results can be obtained on request). We just calculated dG_diss based
on DFT/COSMO and added the statistical thermodynamics contribution from
COSMO-RS. We got a single very good linear correlation of dG_diss with pKa
for a very broad range of organic and inorganic acids. It is  probably the
most accurate "ab initio" prediction of pKa. Nevertheless there is a serious
problem with the slope of the regeression line which is discussed in detail
in the paper: 
A. Klamt, F. Eckert, M. Diedenhofen, and M.E. Beck, "First Principles
Calculations of Aqueous pKa Values for Organic and Inorganic Acids Using
COSMO-RS Reveal an Inconsistency in the Slope of the pKa Scale", J. Phys.
Chem. A., 107, 9380 - 9386 (2003)
Andreas Klamt

Orginal question:

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...

--------

Theodorus de Bruin
Institut Frangais du Pitrole
Direction Chimie et Physico-Chimie Appliquies
Dipartement Thermodynamique et Modilisation Moliculaire
1 & 4 Avenue de bois Preau
92852 Rueil-Malmaison Cedex
Tel: +33 (0)1.47.52.54.38
Fax: +33 (0)1.47.52.70.58