Systematic Approach to Solvent Selection for Biphasic Systems with a Combination of COSMO‐RS and a Dynamic Modeling Tool

Biphasic aqueous‐organic systems are important reaction systems for catalytic processes. This is especially true for biocatalysis where the range of accessible products can be significantly extended. In such systems, the aqueous phase is the reactive phase in which the biocatalyst is dissolved and the organic phase is nonreactive and acts as substrate reservoir and as in situ product extraction solvent. Here, the choice of the nonreactive phase is highly important for the overall performance of the system. In this contribution, a systematic approach to solvent selection for biphasic aqueous‐organic systems is presented with respect to partition coefficients. The model reaction is the stereoselective carbon‐carbon coupling of two 3,5‐dimethoxy‐benzaldehyde molecules to (R)‐3,3',5,5'‐tetramethoxy‐benzoin catalyzed by benzaldehyde lyase (EC 4.1.2.38) from Pseudomonas fluorescens. A systematic approach to solvent selection consisting of two steps is proposed: Firstly, the conductor‐like screening model for real solvents (COSMO‐RS) is used to facilitate a fast solvent screening. Since this is an ab initio approach it allows a pre‐screening without laborious experimental input. The proposed ranking of solvents, based on the ratio of partition coefficients at infinite dilution, is a sound basis for the successive steps. Secondly, a dynamic model is fitted to experimental data in order to obtain detailed and reliable results for mass transfer and partition coefficients. Therefore, the method makes efficient use of the experimental data and substantiates quantitative results with guided experiments.