In this experiment for an introductory undergraduate organic chemistry lab, students tetraalkylate tertbutylcalix[4]arene, a bowl-shaped macrocyclic oligophenol, and examine the supramolecular chemistry of the tetraether product by proton nuclear magnetic resonance (NMR) spectroscopy. Complexation with a sodium ion reduces the conformational mobility of the macrocycle through host-guest interactions, greatly simplifying the [superscript 1]H NMR spectrum of the macrocycle and providing an excellent example of geminal coupling between the diastereotopic protons of the methylene bridges. By dealing explicitly with the organic chemistry of large molecules and host-guest complementarity, this experiment provides a useful pedagogical bridge from small-molecule organic chemistry to the biochemistry of macromolecules such as enzymes.