Coordination-Driven Switching of a Preorganized and Cooperative Calix(4)pyrrole Receptor

The study of preorganization in receptors, particularly in cooperative receptors, and their reversible control by external stimuli is important for elucidating design strategies that can lead to increased sensitivity and external control of molecular recognition. In this work we present the design, synthesis, and operation of an asymmetric tetrathiafulvalene (TTF)-calix[4]pyrrole receptor appended with a pyridine moiety. ¹H NMR spectroscopy was employed to demonstrate that intramolecular complexation between the receptor and the pyridine moiety leads to a preorganized receptor. Absorption and ¹H NMR spectroscopy along with a computational investigation were used to demonstrate the ability of the receptor to complex the substrate 1,3,5-trinitrobenzene (TNB) and that the receptor can be reversibly modulated between negative and positive cooperativity by employing external stimuli in the form of Zn ^II. Fitting procedures incorporating multiple datasets and fitting to multiple equilibria simultaneously have been employed to quantitatively determine the preorganization effects. Zinc's a turn on! The molecular recognition of an asymmetric tetrathiafulvalene (TTF)-calix[4]pyrrole receptor can be reversibly switched between positive and negative cooperativity, when binding 1,3,5-trinitrobenzene (TNB), by chemical stimuli in the form of Zn ^II (see figure). An intramolecular complexation promotes a preorganized receptor with an increased affinity for TNB with a 237-fold increase in the first complexation (K ₁).