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

Renuka Baral, Jackson V. Gunn, and C. Scott Hartley*
ChemRxiv
[Preprint]

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, where each successive binding occurs with the same equilibrium constant. Here we describe an activity for introductory organic 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 equilibria and consider their results in the context of molecular-level interactions.