A general method for extracting individual coupling constants from crowded 1H NMR spectra

Abstract

Couplings between protons, whether scalar or dipolar, provide a wealth of structural information. Unfortunately, the high number of 1H-1H couplings gives rise to complex multiplets and severe overlap in crowded spectra, greatly complicating their measurement. Many different methods exist for disentangling couplings, but none approaches optimum resolution. Here, we present a general new 2D J-resolved method, PSYCHEDELIC, in which all homonuclear couplings are suppressed in F2, and only the couplings to chosen spins appear, as simple doublets, in F1. This approaches the theoretical limit for resolving 1H-1H couplings, with close to natural linewidths and with only chemical shifts in F2. With the same high sensitivity and spectral purity as the parent PSYCHE pure shift experiment, PSYCHEDELIC offers a robust method for chemists seeking to exploit couplings for structural, conformational, or stereochemical analyses. Finding a needle in a haystack: Measurement of 1H-1H couplings in very crowded 1H NMR spectra is made straightforward by a general new method, PSYCHEDELIC. This resolves individual couplings at near-ideal resolution, without interference from other splittings, with good tolerance to strong coupling, and at high sensitivity.