Selectively Enhanced 1H–1H Correlations in Proton-Detected Solid-State NMR under Ultrafast MAS Conditions

Proton-detected solid-state NMR has emerged as a powerful analytical technique in structural elucidation via 1H–1H correlations, which are mostly established by broadband methods. We propose a new class of frequency-selective homonuclear recoupling methods to selectively enhance 1H–1H correlations of interest under ultrafast magic-angle spinning (MAS). These methods, dubbed as selective phase-optimized recoupling (SPR), can provide a sensitivity enhancement by a factor of ∼3 over the widely used radio-frequency-driven recoupling (RFDR) to observe 1HN–1HN contacts in a protonated tripeptide N-formyl-Met-Leu-Phe (fMLF) under 150 kHz MAS and are successfully utilized to probe a long-range 1H–1H contact in a pharmaceutical molecule, the hydrochloride form of pioglitazone (PIO-HCl). SPR is not only highly efficient in frequency-selective recoupling but also easy to implement, imparting to it great potential to probe 1H–1H contacts for the structural elucidation of organic solids such as proteins and pharmaceuticals under ultrafast MAS conditions.