Sweet spot matching: A thin-layer chromatography-based countercurrent solvent system selection strategy ☆

Abstract TLC-based strategies were proposed in 1979 (Hostettmann et al.) and 2005 (Friesen & Pauli; GUESS method) to minimize the number of partitioning experiments required for countercurrent separation (CCS) solvent system selection. As semi-empirical approaches, both proposed that the K values defining the sweet spot of optimal CCS corresponded to a matching R f value range from the silica gel TLC plate developed in the organic phase of a biphasic or a corresponding monophasic solvent system. Despite their simplicity, there has been an absence of theoretical support and a deficiency of reported experimental evidence. The present study explores the theory required to develop correlations between R f and K. All theoretical models surmise that the optimal R f value range should be centered at 0.5. In order to validate the feasibility of the concept of matching R f and K values, 43 natural products and six solvent system families were investigated. Out of 62 correlations, 45 resulted in matched R f and K values. Based on this study, practical guidelines for the TLC-based prediction strategy are provided. These approaches will equip CCS users with an updated understanding of how to apply the TLC-based solvent system selection strategy to accelerate a targeted selection of CCS conditions.