Efficient 13C-13C correlations obtained by AL FRESCO mixing schemes under any arbitrary MAS spinning rates

An efficient chirp pulse-based mixing technique, Adiabatic Linearly FREquency Swept reCOupling (AL FRESCO), is introduced for establishing broadband two-dimensional (2D) 13C-13C dipolar correlations in uniformly 13C-labeled protein samples. AL FRESCO utilizes a single or a series of frequency-swept (chirped) pulses applied to homonuclear spin pairs (e.g., 13Cs, 15Ns, or 1Hs) to mediate homonuclear correlations under magic-angle spinning (MAS). Originally developed for ultrafast MAS, we demonstrate that AL FRESCO performs robustly across a wide range of MAS rates. The AL FRESCO method exhibits strong immunity to dipolar truncation, allowing efficient recoupling of long-range interactions even in the presence of dominant short-range dipolar couplings and regardless of the chemical shift difference between the recoupled sites. A distinctive feature of AL FRESCO is its use of weak radiofrequency (rf) fields (5-20 kHz), independent of the MAS rate, significantly reducing sample heating and enabling extended mixing times (>1 s). This facilitates the observation of long-range correlations that are often inaccessible using conventional recoupling techniques under ultrafast MAS rates. The effectiveness of the method is governed by key parameters such as rf amplitude and envelope shape, dwell time (Δt), and sweep bandwidth. Numerical simulations and average Hamiltonian theory offer insight into the recoupling mechanism. Experimental validation was carried out via 2D 13C-13C correlation spectroscopy at fast, moderate, and slow MAS rates using three different protein systems: uniformly 13C,15N-labeled transthyretin, selectively 13C-[T,W]-labeled CrgA, and uniformly 13C,15N-labeled GB1.