A theoretical framework for efficient solvent suppression in solid-state NMR: Circumventing solvent-signal refocusing by adiabatic-inversion-based dephasing.

We recently developed a solvent-suppression scheme employing adiabatic-inversion pulses for high-resolution solid-state NMR (SSNMR), termed Solvent suppression of Liquid signal with Adiabatic Pulse (SLAP) [T. Matsunaga et al., J. Biomol. NMR 75, 365 (2021)], and demonstrated its superior performance over the traditional MISSISSIPPI scheme [D.H. Zhou et al., J. Magn. Reson. 192, 162 (2008)]. Here, we present a theoretical framework explaining this advantage. We show that MISSISSIPPI-based suppression is intrinsically limited by solvent-signal refocusing. Theory and simulations revealed that up to 50% of the solvent signal was reintroduced after 60 ms of the MISSISSIPPI period. Experiments on 1H methyl solvent signals of 2-methylpentane-2,4-diol (MPD) and isopropanol (IPA) in a microcrystalline sample of immunoglobulin-binding protein G (GB1) confirmed a persistent residual signal (~10%), consistent with the theoretical analyses. In contrast, for the SLAP scheme, which combines a CW-pulse period (τ) and an adiabatic-inversion-pulse train period (τinv), theory, simulations, and experiments demonstrated that, by design, SLAP circumvents echo formation and dissipates residual signals rapidly when τinv≳ 3τ. In 1H-detected 2D 1H/13C correlation SSNMR experiments on the uniformly 13C, 15N-labeled GB1 sample at a magic-angle-spinning (MAS) rate of 60 kHz, SLAP provided a 2.6-fold improvement in solvent suppression relative to MISSISSIPPI within 60 ms. Furthermore, a 5.9-fold improvement in solvent suppression by SLAP was achieved over MISSISSIPPI in 1H-detected 3D 1H/13C/15N correlation experiments on the GB1 sample at a MAS rate of 70 kHz. A similar 5.6-fold improvement by SLAP was observed for water suppression in 1H-detected 2D 1H/13C correlation experiments on a highly hydrated (70% H2O) uniformly 13C, 15N-labeled 0N3R tau amyloid fibril sample at a MAS rate of 70 kHz. These results establish adiabatic-inversion-based dephasing as a robust approach for solvent suppression in SSNMR.