Job plots are often used by researchers to study the interactions of host–guest complexes and their stoichiometries. However, when the method was first described by Paul Job in the 1920s it was used for strong ion associations, not the weak, non-covalent interactions that dominate supramolecular systems. Janusz Jurczak and colleagues at the Polish Academy of Sciences have now shown that in many cases Job's method can give false results. This is especially true when working at low concentrations, or if studying systems with weak binding interactions, more than one binding mode, or even stoichiometries higher than 1:1. Using an inaccurate binding model will lead to association constants (and other related data) that are meaningless.
As an alternative, the researchers suggest analysing residual distributions to assess binding modes when fitting experimental association data. If the correct model is used, the residuals will be distributed randomly. This method is much more sensitive than using a Job plot and can be incorporated into any titration using standard data analysis software. Adoption of these practices will lead to the reporting of significantly more accurate data on associative interactions, such as those in sensing and recognition technology, and improve our understanding of more complex systems.