Spin Relays Enable Efficient Long-Range Heteronuclear Signal Amplification By Reversible Exchange

A systematic experimental study is reported on the polarization transfer to distant spins, which do not directly bind to the polarization transfer complexes employed in Signal Amplification By Reversible Exchange (SABRE) experiments. Both, long-range transfer to protons and long-range transfer to heteronuclei i.e. ¹³C and ¹⁵N are examined. Selective destruction of hyperpolarization on ¹H, ¹³C, and ¹⁵N sites is employed, followed by their re-hyperpolarization from neighboring spins within the molecules of interest (pyridine for ¹H studies and metronidazole-¹⁵N₂-¹³C₂ for ¹³C and ¹⁵N studies). We conclude that long-range sites can be efficiently hyperpolarized when a network of spin-½ nuclei enables relayed polarization transfer (i.e. via short-range interactions between sites). In case of proton SABRE in the milli-Tesla regime, a relay network consisting of protons only is sufficient. However, in case ¹³C and ¹⁵N are targeted (i.e. via SABRE in SHield Enables Alignment Transfer to Heteronuclei or SABRE-SHEATH experiment), the presence of a heteronuclear network (e.g. consisting of ¹⁵N) enables a relay mechanism that is significantly more efficient than the direct transfer of spin order from para-H₂-derived hydrides.