Cycloalkane and Alicyclic Heterocycle Complexation by New Switchable Resorcin[4]arene-Based Container Molecules: NMR and ITC Binding Studies

• Published in: Chemistry : a European journal 2011-10, Vol.17 (44), p.12362-12371
• Main Authors: Hornung, Jens, Fankhauser, Daniel, Shirtcliff, Laura D., Praetorius, Antonia, Schweizer, W. Bernd, Diederich, François
• Format: Article
• Language: English
• Subjects: Chemistry; container molecules; controllable encapsulation; Crystal structure; host-guest systems; molecular recognition; supramolecular chemistry
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201101861

The synthesis and structural characterization of novel, “molecular basket”‐type bridged cavitands is reported. The resorcin[4]arene‐based container molecules feature well‐defined cavities that bind a wide variety of cycloalkanes and alicyclic heterocycles. Association constants (Ka) of the 1:1 inclusion complexes were determined by both 1H NMR and isothermal titration calorimetry (ITC). The obtained Ka values in mesitylene ranged from 1.7×102 M−1 for cycloheptane up to 1.7×107 M−1 for morpholine. Host–guest complexation by the molecular baskets is generally driven by dispersion interactions, CH⋅⋅⋅π interactions of the guests with the aromatic walls of the cavity, and optimal cavity filling. Correlations between NMR‐based structural data and binding affinities support that the complexed heterocyclic guests undergo additional polar CO⋅⋅⋅CO, NH⋅⋅⋅π, and S⋅⋅⋅π interactions. The first crystal structure of a cavitand‐based molecular basket is reported, providing precise information on the geometry and volume of the inner cavity in the solid state. Molecular dynamic (MD) simulations provided information on the size and conformational preorganization of the cavity in the presence of encapsulated guests. The strongest binding of heterocyclic guests, engaging in polar interactions with the host, was observed at a cavity filling volume of 63 ± 9 %. The host–guest complexes of cycloalkanes and alicyclic heterocycles with new cavitand‐based molecular baskets were comprehensively investigated by 1H NMR spectroscopy and ITC analysis in mesitylene. Polar interactions between host and guest strengthened heterocycle binding, and six‐membered‐ring guests afforded the best fit based upon the interior cavity volume. The ability of the basket to act as a selective host for alicyclic guests was externally controlled by pH modulation.