  EXSY, TOCSY and NOESY lie at the foundation of homonuclear NMR experiments in
organic and pharmaceutical chemistry, as well as in structural biology. Limited
magnetization transfer efficiency is an intrinsic downside of these methods,
particularly when targeting rapidly exchanging species such as labile protons
ubiquitous in polysaccharides, sidechains and backbones of proteins, and in
bases and sugars of nucleic acids: the fast decoherence imparted on these
protons through solvent exchanges, greatly reduces their involvement in
homonuclear correlation experiments. We have recently discussed how these
decoherences can be visualized as an Anti-Zeno Effect, that can be harnessed to
enhance the efficiency of homonuclear transfers within Looped PROjected
SpectroscopY (L-PROSY) leading to 200-300% enhancements in NOESY and TOCSY
cross-peaks for amide groups in biomolecules. This study demonstrates that even
larger sensitivity gains per unit time, equivalent to reductions by several
hundred-folds in the duration of experiments, can be achieved by looping
inversion or using saturation procedures. In the ensuing experiments a priori
selected frequencies are encoded according to Hadamard recipes, and
subsequently resolved along the indirect dimension via linear combinations.
Magnetization-transfer (MT) processes reminiscent of those occurring in CEST
provide significant enhancements in the resulting cross-peaks, in only a
fraction of acquisition time of a normal 2D experiment. The effectiveness of
the ensuing three-way polarization transfer interplay between water, labile and
non-labile protons was corroborated experimentally for proteins,
homo-oligosaccharides and nucleic acids. In all cases, cross-peaks barely
detectable in conventional 2D NMR counterparts, were measured ca. 10-fold
faster and with 200-600% signal enhancements by the Hadamard MT counterparts.
