Prediction of acidity in acetonitrile solution with COSMO-RS

✍ Scribed by Frank Eckert; Ivo Leito; Ivari Kaljurand; Agnes Kütt; Andreas Klamt; Michael Diedenhofen

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 139 KB
• Volume: 30
• Category: Article
• ISSN: 0192-8651
• DOI: 10.1002/jcc.21103

✦ Synopsis

Abstract

The COSMO‐RS method, a combination of the quantum chemical dielectric continuum solvation model COSMO with a statistical thermodynamics treatment for realistic solvation simulations, has been used for the prediction of p__K__~a~ values in acetonitrile. For a variety of 93 organic acids, the directly calculated values of the free energies of dissociation in acetonitrile showed a very good correlation with the p__K__~a~ values (r^2^ = 0.97) in acetonitrile, corresponding to a standard deviation of 1.38 p__K__~a~ units. Thus, we have a prediction method for acetonitrile p__K__~a~ with the intercept and the slope as the only adjusted parameters. Furthermore, the p__K__~a~ values of CH acids yielding large anions with delocalized charge can be predicted with a rmse of 1.12 p__K__~a~ units using the theoretical values of slope and intercept resulting in truly ab initio p__K__~a~ prediction. In contrast to our previous findings on aqueous acidity predictions the slope of the experimental p__K__~a~ versus theoretical Δ__G__~diss~ was found to match the theoretical value 1/RT ln (10) very well. The predictivity of the presented method is general and is not restricted to certain compound classes. However, a systematic correction of −7.5 kcal mol^−1^ is required for compounds that do not allow electron‐delocalization in the dissociated anion. The prediction model was tested on a diverse test set of 129 complex multifunctional compounds from various sources, reaching a root mean square deviation of 2.10 p__K__~a~ units. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009