Improving SABRE hyperpolarization with highly nonintuitive pulse sequences: Moving beyond avoided crossings to describe dynamics

Abstract

Signal amplification by reversible exchange (SABRE) creates “hyperpolarization” (large spin magnetization) using a transition metal catalyst and parahydrogen, addressing the sensitivity limitations of magnetic resonance. SABRE and its heteronuclear variant X-SABRE are simple, fast, and general, but to date have not produced polarization levels as large as more established methods. We show here that the commonly used theoretical framework for these applications, which focuses on avoided crossings (also called level anticrossings or LACs), steer current SABRE and X-SABRE experiments away from optimal solutions. Accurate simulations show astonishingly rich and unexpected dynamics in SABRE/X-SABRE, which we explain with a combination of perturbation theory and average Hamiltonian approaches. This theoretical picture predicts simple pulse sequences with field values far from LACs (both instantaneously and on average) using different terms in the effective Hamiltonian to strategically control evolution and improve polarization transfer. Substantial signal enhancements under such highly nonintuitive conditions are verified experimentally.

Advancing homogeneous catalysis for parahydrogen-derived hyperpolarisation and its NMR applications

“…Novel pulse sequences have also been used as a route to achieve high polarisation by compensating for suboptimal ligand exchange processes. 148 …”

“…Novel pulse sequences have also been used as a route to achieve high polarisation by compensating for suboptimal ligand exchange processes. 148 Catalysts involved in early SABRE studies contained an auxiliary phosphine ligand and were of the form [Ir(H) 2 (-PCy 3 )(substrate) 3 ][BF 4 ], where Cy is cyclohexyl. It was soon noted that the identity of the auxiliary phosphine ligand was one of many important factors that determine the efficiency of SABRE catalysis and the resulting NMR signal enhancements that can be achieved.…”

SABRE enhancement with oscillating pulse sequences

“…For continuous wave excitation in SABRE/X-SABRE, we recently pointed out 23 that the level anticrossing 12,29–32 condition does not even give qualitatively correct predictions except for very small couplings and very slow exchange. For example, in the case of the AA′B system shown in Fig.…”

“…Specifically, ref. 23 shows that an alternating two-field pulse sequence (both fields high, but with a small average) can produce very large SABRE enhancements. In fact, two papers on similar field manipulations were submitted shortly after that work.…”

“…However, the amount of polarization produced at any one time is generally lower than with d-DNP or SEOP, although there is no fundamental reason why this must be true. We have recently shown 23 that a big part of the reason is that the novel field regime for SABRE and X-SABRE (where even heteronuclear couplings can be readily interconverted between the strong and weak coupling limits), combined with the very complex exchange dynamics, imply that the method is theoretically underexplored; there are clearly better (but nonintuitive) approaches to creating polarization than a simple continuous field. Specifically, ref.…”