Proton-observed carbon-edited NMR spectroscopy in strongly coupled second-order spin systems

Proton-observed carbon-edited (POCE) NMR spectroscopy is commonly used to measure ¹³C labeling with higher sensitivity compared to direct ¹³C NMR spectroscopy, at the expense of spectral resolution. For weakly coupled first-order spin systems, the multiplet signal at a specific proton chemical shift in POCE spectra directly reflects ¹³C enrichment of the carbon attached to this proton. The present study demonstrates that this is not necessarily the case for strongly coupled second-order spin systems. In such cases NMR signals can be detected in the POCE spectra even at chemical shifts corresponding to protons bound to ¹²C. This effect is demonstrated theoretically with density matrix calculations and simulations, and experimentally with measured POCE spectra of [3-¹³C] glutamate.