Strong, Size-Selective, and Electronically Tunable C−H···Halide Binding with Steric Control over Aggregation from Synthetically Modular, Shape-Persistent [34]Triazolophanes

Abstract

A series of shape-persistent [3(4)]triazolophanes bearing t-butyl or triethylene glycol (OTg) substituents on the phenylene linkers have been prepared in a modular manner from simple building blocks. Triazolophane-halide binding affinities were determined using UV titrations in order to help in understanding the driving forces behind the large receptor-anion binding strengths supported solely by CH hydrogen-bond donors. The fixed size of the central cavity provides a means for selective recognition of Cl(-) and Br(-) anions with large binding strengths (Ka > 1,000,000 M(-1); DeltaG > -8.5 kcal mol(-1)). The smaller F(-) and larger I(-) anions are bound less tightly by approximately 1 and approximately 3 orders of magnitude, respectively. The four triazole-based H-bond donors are believed to be of primary importance, while the four phenylene CH H-bond donors take on a secondary role. Consistent with this idea, the binding affinity can be tuned by as much as 1 kcal mol(-1) by changing the character of the four phenylene-based substituents from more (OTg) to less (t-butyl) electron-donating. Preorganization was also found to play a central role, on the basis of comparisons with a foldamer analogue that shows much-reduced binding. Aggregation was facilitated as the substituents were changed from t-butyl to OTg, increasing the degree of self-association from K(E) approximately = 0 to 230 M(-1) in CD2Cl2. Diffusion NMR experiments established aggregation as opposed to dimerization. These findings indicate the importance of the cavity size for selective anion recognition as well as the role of the phenylene linkers in tuning the binding strengths and modulating the aggregation of the [3(4)]triazolophanes.