Abstract: Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are both characterized by a low level of sensitivity which is attributed to the low thermal polarization of nuclear spins. Nuclear spin hyperpolarization provides a highly effective solution for improving the sensitivity of NMR and MRI up to several orders of magnitude, which is based on the preparation of the non-equilibrium nuclear magnetization. Parahydrogen Induced Polarization (PHIP) [1] is a hyperpolarization technique that uses parahydrogen, a non-magnetic spin isomer of molecular hydrogen, as a means to enhance NMR signals. Despite being NMR-silent, parahydrogen possesses nuclear spin order that can be transferred to the nuclear magnetization of the target molecule. This, in turn, requires parahydrogen to be involved in a symmetry-breaking chemical process. In hydrogenative PHIP, the substrate with unsaturated bonds is hydrogenated by parahydrogen in the presence of a homogeneous or heterogenous catalyst. This gives rise to strong enhancement of the 1H NMR signals of the hydrogenation product. In signal amplification by reversible exchange (SABRE) [2], which is also termed as non-hydrogenative PHIP, a parahydrogen and substrate molecule participate in reversible interactions with an Ir-based catalytic complex, as demonstrated in Fig. 1 a. During the transient bonding of the substrate and parahydrogen with the polarization transfer complex (PTC), the substrate acquires polarization due to the J-couplings with the hydride 1H nuclei stemmed from a parahydrogen molecule. The following dissociation of the substrate from the PTC leads to formation of the hyperpolarized substrate in bulk. Typically, heteronuclear polarization transfer by SABRE occurs in magnetic shields. This method is termed as SABRE-SHEATH (SHield Enables Alignment Transfer to Heteronuclei) [3], which involves transferring the sample from the NMR spectrometer to a zone with an ultralow magnetic field, BULF (smaller than 1 μT), as shown in Fig 1 b. This procedure is performed to meet the strong coupling condition between the heteronuclei and protons. Ultralow magnetic fields are usually provided by magnetic shields, which compensate the magnetic field of the Earth. To the date, this is the most conventional technique for efficient (> 10% of polarization) heteronuclear SABRE hyperpolarization. Whereas 13C and 15N nuclei are common targets for SABRE hyperpolarization, hyperpolarization of other heteronuclear spins is challenging. One such example is the 77Se nucleus, which is a magnetic isotope of selenium (s=½). Low natural abundance (7.603 %) and small value of nuclear magnetic momentum of the 77Se nucleus (which is 1.3-fold smaller than magnetic momentum of the 13C nucleus) results in inherently low sensitivity of the 77Se NMR spectroscopy. This significantly limits the practical applications of the 77Se NMR spectroscopy, which is very informative due to 77Se nuclei exhibit a large chemical shift dispersion of over 3000 ppm. This property of 77Se nuclei makes them a useful probe for organic synthesis, biological studies in vivo and temperature sensing [4]. To the best of our knowledge, only one publication dedicated to the 77Se hyperpolarization is present, where dissolution dynamic nuclear polarization (d-DNP) has been used to hyperpolarize 77Se nuclei in sodium selenite and sodium sulfate [5]. Therefore, in this work, we examine the feasibility of hyperpolarization of 77Se nuclei using SABRE. We demonstrate efficient hyperpolarization of 77Se nuclei (7.0 ± 0.8 % of 77Se polarization) using signal amplification by reversible exchange (SABRE) at ultralow magnetic fields of a microtesla range. The 77Se hyperpolarization was performed for a biologically relevant molecule, 3-methyl-[1,2,4]-selenadiazolo-[4,5-a]-pyridine-4-ium chloride (SDAP). The most efficient hyperpolarization of 77Se nuclei was achieved for the 15N-77Se istopologue of SDAP (0.028 % natural abundance) which contains two different types of heteronuclear spins. We show that the 77Se nuclei of SDAP acquire polarization in the polarization transfer complex in a relayed manner via the J-coupling with the complex-coordinating 15N nucleus. Therefore, this work paths the road for the following optimization of polarization transfer on 77Se or other heteronuclei with s=½ by SABRE, especially in spin systems containing several types of heteronuclei (e.g. using RF excitation at low magnetic fields).

Cite: Kiryutin A.S. , Markelov D.A. , Kosenko I.D. , Osmanov V.K. , Godovikov I.A. , Yurkovskaya A.V.
Spin Hyperpolarization Of 77Se Nuclei Using Signal Amplification By Reversible Exchange (SABRE) At Microtesla Fields
22nd International School-Conference MAGNETIC RESONANCE AND ITS APPLICATIONS 31 Mar - 4 Apr 2025