Quantifying the association of caffeine using NMR spectroscopy in the organic chemistry laboratory

Renuka Baral, Jackson V. Gunn, and C. Scott Hartley*
J. Chem. Educ., in press
[Published version | Preprint]

Table of Contents figure, which depicts a stack of three caffeine molecules and a plot of chemical shift vs caffeine concentration.

Abstract

The self-association of caffeine in solution, driven by the hydrophobic effect, is a simple example of molecular aggregation. It obeys an isodesmic association model in which each successive binding occurs with the same equilibrium constant. Here, we describe an activity for chemistry students that explores this phenomenon using nuclear magnetic resonance (NMR) spectroscopy. By analyzing concentration-dependent chemical shift changes in the ¹H NMR spectra of caffeine dissolved in D₂O, students are introduced to uses of NMR spectroscopy beyond structure elucidation. They gain hands-on experience in quantifying supramolecular equilibria and consider their results in the context of molecular-level interactions.