NMR case study of ropinirole: Concentration-dependent effects of nonexchangeable proton resonances

NMR is an established technique that is commonly used for structure characterization and determination of purity of small molecules. It is generally accepted that nonexchangeable protons of chemical structures show a characteristic chemical shift and signal multiplicity depending on the local geometry, such as binding partners, bond lengths and binding angle. The chemical shifts of nonexchangeable protons, unlike for exchangeable protons, are typically independent from the sample concentration. However, significant changes in chemical shifts of nonexchangeable protons have been previously reported for a range of scaffolds including quinolones, indoles, benzofurans, naphthalenes and other related structures. Details about the concentration of a sample are generally not reported for NMR experiments; however, unidentified as well as unreported concentration-dependent NMR effects complicate the reproducibility and comparison of spectral data from different experiments and potentially lead to false interpretation of results.