Validation of the Direct-COSMO-RS Solvent Model for Diels–Alder Reactions in Aqueous Solution

Abstract

The modeling of chemical reactions in protic solvents tends to be far more computationally demanding than in most aprotic solvents, where bulk solvent effects are well described by dielectric continuum solvent models. In the presence of hydrogen bonds from a protic solvent to reactants, transition states or intermediates, a faithful modeling of the solvent effects usually requires some kind of molecular dynamics treatment. In contrast, the COSMO-RS (conductor-like screening model for real solvents) approach has been known for about a decade to describe protic solvent effects much better than continuum solvents, in spite of being an implicit solvent model without explicit molecular dynamics. More recently, the self-consistent use of its potential in electronic-structure methods has led to the Direct-COSMO-RS approach. It allows, for example, structure optimization in the presence of a protic solvent, of solvent mixtures, as well as self-consistent property calculations. In view of recent successful tests for electron transfer in organic mixed-valence systems, in this work the wider applicability of D-COSMO-RS for organic reactivity is evaluated by computation of activation and reaction free energies, as well as transition-state structures of two prototypical Diels–Alder reactions, with an emphasis on aqueous solution. D-COSMO-RS indeed provides substantial improvements over the COSMO continuum model and in judicious testing compares well with embedded supermolecular model cluster treatments, without prior knowledge about the average numbers of hydrogen-bonding interactions present