NMR Reaction Monitoring Robust to Spectral Distortions.

Nuclear magnetic resonance spectroscopy (NMR) is one of the most potent analytical chemistry methods, providing unique insight into molecular structures. Its noninvasiveness makes it a perfect tool for monitoring chemical reactions and determining their products and kinetics. Typically, the reactions are monitored by a series of H NMR spectra acquired at regular time intervals. Even such a straightforward approach, however, often suffers from several problems. In particular, the reaction may cause sample inhomogeneity, resulting in a nonhomogenous magnetic field and distorted spectral lineshapes. When the studied process is fast, hardware correction (shimming and locking) cannot be applied on the fly, and the spectral quality degrades over the course of the reaction. Moreover, when nondeuterated solvents have to be used in the reaction mixture, a magnetic field-stabilizing system (deuterium lock) cannot work. Consequently, the spectra have distorted lineshapes, reduced resolution, and randomly varying peak positions, making them challenging to analyze quantitatively with standard software. In this paper, we propose a conceptually new approach to the quantitative analysis of a series of distorted spectra. The method is based on the Wasserstein distance and can effectively quantify the components of a reaction mixture without the need for peak-picking. We provide open-source software requiring minimum input from the user, i.e., a set of spectra indexed by time.