Cloud point extraction of pyridine <i>N</i> -oxides using mixed micelles of PEGylated calix[4]pyrroles and non-ionic surfactants

Pyridine <i>N</i>-oxides occur in pharmaceuticals and agrochemicals as solubilizing groups or as products of the oxidative metabolism of pyridine derivatives. Aryl-extended calix[4]pyrroles are supramolecular hosts that selectively bind pyridine <i>N</i>-oxides in host-guest complexes. A micelle-mediated extraction method was developed for the selective extraction of pyridine <i>N</i>-oxides from aqueous solutions using mixed micelles composed of aryl-extended calix[4]pyrroles and the non-ionic surfactants Triton X-100 and Tergitol 15-S-7. To this end, aryl-extended calix[4]pyrroles were functionalized with three different methoxy polyethylene glycol chains, and their binding constants for pyridine <i>N</i>-oxide and <i>p</i>-phenylpyridine <i>N</i>-oxide were determined with NMR titrations in DMSO-<i>d</i> ₆ and D₂O. The effect of calix[4]pyrroles on the cloud point temperature of Triton X-100 was measured, and the hydrodynamic diameters of Triton X-100/calix[4]pyrrole mixed micelles were characterized using dynamic light scattering. The extraction efficiency of different calix[4]pyrrole/surfactant mixtures were evaluated. Notably, pyridine <i>N</i>-oxides showed no interaction with either Triton X-100 or Tergitol alone and at the investigated analyte concentration the calix[4]pyrrole does not reach cloud point, prompting the use of mixed micelles in which the calix[4]pyrrole binds pyridine <i>N</i>-oxide and the surfactant provides the clouding properties. The developed calix[4]pyrrole system represents the first example of cloud point extraction of pyridine <i>N</i>-oxides.