20DRUG SOLUBILITY, REACTION THERMODYNAMICS, AND CO‐CRYSTAL SCREENING

Karin Wichmann and Christoph Loschen

COSMO logic GmbH & Co. KG, Leverkusen, Germany

Andreas Klamt

COSMO logic GmbH & Co. KG, Leverkusen, Germany and Institute of Physical and Theoretical Chemistry, University of Regensburg, Regensburg, Germany

20.1 INTRODUCTION

20.1.1 Methods for Compounds in Solution

There is a variety of computational methods for the treatment of compounds in solution. The scope of this chapter is not to give an overview of them, but to concentrate on applications of COSMO‐RS, a very efficient method for the a priori prediction of thermophysical data of liquids. COSMO‐RS combines unimolecular quantum chemical calculations that provide the necessary information for the evaluation of molecular interaction in the fluid phase, with a very fast and accurate statistical thermodynamic procedure. It has established itself as an alternative to structure‐based group contribution methods (GCMs) on the one hand and to force field‐based simulation methods on the other hand. Because of its special approach, COSMO‐RS is a generally applicable method for compounds in solution. It has been applied successfully in such diverse areas as solvent screening, partitioning behavior, liquid–liquid and vapor–liquid equilibria, and ADME property prediction and for such diverse compound types as drugs, pesticides, common organic compounds, halocarbons, and ionic liquids. COSMO‐RS is used in chemical, pharmaceutical, ...

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