From chemistry-request@ccl.net Tue Mar 2 08:35:07 2004 Received: from irsun275.ifp.fr (ns2.ifp.fr [81.255.42.34]) by server.ccl.net (8.12.8/8.12.8) with ESMTP id i22DZ6d4029344 for ; Tue, 2 Mar 2004 08:35:07 -0500 Received: from smtp.ifp.fr by irsun275.ifp.fr (V35.12) with ESMTP Received: from irnts21.ifp.fr (irnts21 [156.118.15.51]) by irsun165.ifp.fr (8.8.5/8.8.5) with ESMTP id OAA06619 for ; Tue, 2 Mar 2004 14:36:34 +0100 (MET) Received: by irnts21.ifp.fr with Internet Mail Service (5.5.2657.72) id <1M6NZTRR>; Tue, 2 Mar 2004 14:36:33 +0100 Message-ID: <3AA99E087354D61185E4002048403CFC02145B55!at!irnts23.ifp.fr> From: DE BRUIN theodorus To: "'chemistry!at!ccl.net'" Subject: summary : calculation of pka valuse by ab initio methods Date: Tue, 2 Mar 2004 14:36:32 +0100 MIME-Version: 1.0 X-Mailer: Internet Mail Service (5.5.2657.72) Content-Type: text/plain; charset="iso-8859-1" Content-Transfer-Encoding: 8bit X-MIME-Autoconverted: from quoted-printable to 8bit by server.ccl.net id i22DZ7d4029345 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