SABRE-Relay: A Versatile Route to Hyperpolarization

Abstract

Signal Amplification by Reversible Exchange (SABRE) is used to switch on the latent singlet spin order of para-hydrogen (p-H₂) so that it can hyperpolarize a substrate (sub = nicotinamide, nicotinate, niacin, pyrimidine, and pyrazine). The substrate then reacts reversibly with [Pt(OTf)₂(bis-diphenylphosphinopropane)] by displacing OTf^- to form [Pt(OTf)(sub)(bis-diphenylphosphinopropane)]OTf. The ³¹P NMR signals of these metal complexes prove to be enhanced when the substrate possesses an accessible singlet state or long-lived Zeeman polarization. In the case of pyrazine, the corresponding ³¹P signal was 105 ± 8 times larger than expected, which equated to an 8 h reduction in total scan time for an equivalent signal-to-noise ratio under normal acquisition conditions. Hence, p-H₂ derived spin order is successfully relayed into a second metal complex via a suitable polarization carrier (sub). When fully developed, we expect this route involving a second catalyst to successfully hyperpolarize many classes of substrates that are not amenable to the original SABRE method.

Scheme 1. Schematic Depiction of the SABRE-Relay

Substrate S₁ binds reversibly alongside p-H₂ to metal complex M₁ and becomes hyperpolarized. S₁ then binds reversibly to M₂–S₁ and polarization is relayed into its ³¹P response.

Scheme 2. Identities of S₁ Used in This SABRE-Relay Study

Scheme 3. Relayed Transfer of Polarization from p-H₂ into a Second Agent

Precatalyst [IrCl(IMes)(COD)] (M₁) is transformed into [Ir(H)₂(IMes)(S₁)₃]Cl (M₁–S₁) by adding p-H₂ gas and substrate S₁. S₁ then gains hyperpolarized Zeeman and singlet spin order via polarization transfer from p-H₂ depending on its identity. In a second step, the ³¹P response of M₂–S₁ becomes hyperpolarized.

Figure 1

Experimental scheme for SABRE-Relay, showing timings, magnetic field variance, and rf sequence. First, the sample is mixed with enriched p-H₂ at low magnetic field (∼6 mT and ∼1–10 μT) for the durations of τ_LF1 and τ_LF2 before moving to high field (τ_tr) for NMR observation. A simultaneous 90° pulse is applied to ¹H and ³¹P prior to acquiring the ³¹P signal with ¹H decoupling (protocol 1). In a second variant, protocol 2, an M2S sequence, is applied between τ_LF1 and τ_LF2.

Figure 2

Single-scan ³¹P{¹H} NMR spectra associated with (A) M₂–S_1a, (B) M₂–S_1b, (C) M₂–S_1c, and (D) M₂–S_1d using SABRE-Relay protocol 1 of Figure 1.

Figure 3

³¹P{¹H} NMR spectra associated with M₂–S_1g and M₂–S_1h (structures above the NMR spectra) that form from M₂ and S_1g or S_1h, respectively. In both cases, the upper ³¹P NMR spectrum is the control, which involved 128 transients, while the lower NMR spectrum was acquired by SABRE-Relay through process 1 and associated with a single detection pulse according to Figure 2.