Quantitative ¹H-¹³C BRAIN multiple-CP solid-state NMR

We introduce a broadband approach to quantitative ¹H-¹³C cross-polarization magic-angle-spinning (CPMAS) solid-state NMR spectroscopy based on broadband adiabatic inversion cross-polarization (BRAIN-CP). The method simplifies conventional multiple cross-polarization (Multi-CP) by replacing Hartmann-Hahn CP with BRAIN-CP, in which a chirped pulse applied to ¹³C enables efficient ¹H → ¹³C polarization transfer over a broad offset-frequency range. Multiple BRAIN-CP blocks, separated by polarization-recovery delays, are concatenated to form a BRAIN Multi-CP sequence. Because each BRAIN-CP block directly generates longitudinal ¹³C magnetization, the 90° storage and reconversion pulses required in conventional Multi-CP are eliminated. This simplified sequence reduces errors associated with RF pulse imperfections while providing a substantially broader ¹³C offset-frequency response and more uniform polarization transfer across wide chemical-shift ranges. We further demonstrate that, for uniformly ¹³C-labeled samples, a single BRAIN-CP block followed by ¹³C-¹³C homonuclear recoupling can produce quantitative ¹³C MAS spectra. The methods are validated using uniformly ¹³C-labeled and natural-abundance model compounds, including N-acetylvaline, Ala-Gly-Gly, glucose, and tryptophan. The resulting spectra show accurate relative intensities, improved robustness, and broadband performance, establishing BRAIN Multi-CP as a simplified and effective approach to quantitative ¹³C solid-state NMR spectroscopy.