Higher-Rank Correlation NMR Spectra with Spectral Moment Filtering

Higher-rank correlation spectroscopy is introduced as an alternative to 3D Fourier-transform (FT) NMR spectroscopy for resonance assignment and molecular structure determination. The method combines standard 2D FT spectra that share a common frequency dimension, such as a 2D (13)C-(1)H HSQC and a 2D (1)H-(1)H TOCSY spectrum, and constructs higher-rank correlation spectra with ultra-high spectral resolution. Spectral overlap along a common dimension, in particular the (1)H dimension, is addressed by a spectral filtering method, which identifies mismatches between the 1(st) and 2(nd) moments of cross-peak profiles. The method, which provides a substantial speed-up over traditional 3D FT spectroscopy while effectively suppressing false peaks, is demonstrated for the triple-rank (13)C-(1)H HSQC-TOCSY spectrum of a cyclic decapeptide with different mixing times. Higher-rank correlation spectroscopy is usefully applicable to the analysis of a wide range of NMR spectra of synthetic and natural products.