Calixarenes are macrocyclic receptors with applications in sensors, materials, chemical biology, and medicinal chemistry. This versatility is due to the ability to fix the conformation of the calixarene, so it can be used as a topologically defined platform, or leave it mobile to provide a highly flexible scaffold.
Susan Matthews, University of East Anglia, Norwich, UK, and colleagues have developed the first conformationally switchable calixarene by incorporating a propyne – rather than a propyl group – at the lower rim. Using 1H NMR kinetic studies and molecular modeling techniques, calixarenes in the 1,3-alternate and 1,2-alternate conformations were shown to switch irreversibly to the partial cone. This occurs even at room temperature and can be modulated by choice of starting conformation, by changing the upper-rim substituent, or by the solvent. Surprisingly, conformational change can also occur on heating in the solid state without any observable change in the bulk material.
It was found that 1,2-alternate structures switch to the partial cone rapidly in solution and in the solid state. 1,3-alternate structures switch only in solvent. The ab initio calculations confirmed that the partial cone conformation is the global thermodynamic minimum. According to the researchers, this switchable system offers the potential for the development of calixarene-based stimuli-sensitive materials for drug delivery and ion sensing.
- Fixing the Conformation of Calixarenes: When Are Three Carbons Not Enough?,
Susan E. Matthews, Samy Cecioni, John E. O’Brien, Colin J. MacDonald, David L. Hughes, Garth A. Jones, Stephen H. Ashworth, Sébastien Vidal,
Chem. Eur. J. 2018.