INEPT- and HMQC-based pulse sequences are widely used to transfer polarization between heteronuclei, particularly in biomolecular spectroscopy: they are easy to setup and involve low power deposition. Still, these short-pulse polarization transfers schemes are challenged by fast solvent chemical exchange. An alternative to improve these heteronuclear transfers is J-driven cross polarization (J-CP), which transfers polarization by spin-locking the coupled spins under Hartmann-Hahn conditions. J-CP provides certain immunity against chemical exchange and other T2-like relaxation effects, a behavior that is here examined in depth by both Liouville-space numerical and analytical derivations describing the transfer efficiency. While superior to INEPT-based transfers, fast exchange may also slow down these J-CP transfers, hurting their efficiency. This study therefore explores the potential of repeated projective operations to improve 1H->15N and 1H->15N->13C J-CP transfers in the presence of fast solvent chemical exchanges. It is found that while repeating J-CP provides little 1H->15N transfer advantages over a prolonged CP, multiple contacts that keep both the water and the labile protons effectively spin-locked can improve 1H->15N->13C transfers in the presence of chemical exchange. The ensuing Looped, Concatenated Cross Polarization (L-CCP) compensates for single J-CP losses by relying on the 13C longer lifetimes, leading to a kind of algorithmic cooling that can provide high polarization for the 15N as well as carbonyl and alpha 13Cs. This can facilitate certain experiments, as demonstrated with triple resonance experiments on intrinsically disordered proteins involving labile, chemically exchanging protons.
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