Harnessing Water to Enhance Quadrupolar NMR Spectroscopy and Imaging

(17)O and (14)N are attractive targets for in vivo NMR spectroscopy and imaging, but low gyromagnetic ratios γ and fast spin relaxation complicate observations. This work explores indirect ways of detecting some of these sites with the help of proton‐detected double resonance techniques. As standard coherence transfer methods are of limited use for such indirect detection, alternative routes for probing the quadrupolar spectra on (1)H were tested. These centered on modulating the broadening effects imparted onto protons adjacent to the low‐γ species through J couplings through either continuous wave or spin‐echo double‐resonance decoupling/recoupling sequences. As in all cases, the changes imparted by these double‐resonance strategies were small due to the fast relaxation undergone by the quadrupoles, the sensitivity of these approaches was amplified by transferring their effects onto the abundant water (1)H signal. These amplifications were mediated by the spontaneous exchanges that the labile (1)Hs bound to (17)O or (14)N undergo with the water protons. In experiments designed on the basis of double‐resonance spin echoes, these enhancements were imparted by looping the transverse encodings together with multiple longitudinal storage periods, leading to decoupling‐recoupling with exchange (D‐REX) sequences. In experiments designed on the basis of continuous on/off quadrupolar decoupling, these solvent exchanges were incorporated into chemical‐exchange saturation transfer schemes, leading to decoupling‐recoupling with saturation transfer (D‐REST) sequences. Both of these variants harnessed sizable proportions of the easily detectable water signals, in order to characterize the NMR spectra and/or to image with atomic‐site specificity the (17)O and (14)N species.