Recognizing the Limited Applicability of Job Plots in Studying Host–Guest Interactions in Supramolecular Chemistry

TLDR

The Job plot, a continuous variation method, has been the standard for determining stoichiometry of complex chemical entities for over a century. The authors propose a general alternative method based on residual distribution analysis of titration data fitting. They validate this approach with simulations and case studies of real host–guest systems, analyzing residual distributions in titration data fitting. The Job plot often yields false results for supramolecular host–guest systems, whereas the proposed residual distribution method is more convenient and consistently produces correct results in all studied cases.

Abstract

Continuous variation method, known as Job plot, is the most commonly applied method for the determination of stoichiometry of complex chemical entities for over 100 years. Although, the method was proven successful in the analysis of very stable metal–ligand complexes, we demonstrate that its use in supramolecular chemistry often provides false results. We support this statement with multiple simulations as well as cases studies of several real host–guest systems. We propose an alternative, general method relying on the analysis of residual distribution in titration data fitting. The latter method is more convenient compared to the Job plot and unlike it gives correct results in all real cases studied.