In a previous study by Smith and co-workers, it was shown that receptor 4a could bind to F -in pure DMSO-d6 at 298 K with a Ka of 5.3 (± 0.8) × 10 4 M -1 . The same study also noted that trace amounts of H2O in the DMSO-d6 produced HF2 -, preventing accurate fitting. Initial F -binding studies (using TBAF) were performed with tetralactams 2a and 3a (1 mM) to discover if any difference would be observed in the more competitive DMSO-d6/H2O (0.5%) solvent system (Figure and S72). Immediate peak broadening was observed for the resonances attributed to the N-H and C-H proton peaks after adding the initial aliquot of the F -guest. Further additions above 1 equiv. caused both the amide and isophthalic proton peaks to disappear. Increasing the concentration of F -caused receptor deprotonation, which was indicated by discolouration of the titration solution during binding studies.