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Abstract:
Introduction: Parahydrogen-induced nuclear spin hyperpolarization is a promising tool for signal enhancement with perspective to future biomedical application. The reproducible method Signal Amplification by Reversible Exchange (SABRE)[1,2] enables the generation of always fresh hyperpolarized molecules. Hyperpolarization takes place in an organic solvent and the substrate can be transferred into a biocompatible solution via two-phase transfer. First experiments have already shown the potential but also some hurdles of this approach.[3] The choice of organic solvent plays a major role, as shown below.
Methods: Various organic fluorinated molecules were selected as test substances to investigate the influence of the organic solvent during hyperpolarization in the presence of the Ir-IMes catalyst. By choosing fluorinated molecules (no background signals during measurement), the selection of non-deuterated organic solvents could be extended. The solvents included chloroform, toluene, and xylene. In 2 mL of solvent, 1.7 mg of the Ir-IMes complex were dissolved together with e.g., 4μL of 3-fluoropyridine in a 10mm NMR tube (e. g. Fig.1). Both the activation of the catalyst and the signal amplification to 19F were investigated. The hyperpolarization was realized by using 50% enriched parahydrogen (pH2), 6bar pressure and shaking the sample for 10s at 6mT before transport to 7T for measurements.
Results/Discussion: The results show that hyperpolarization in CHCl3 and toluene can be detected already after the first introduction of hydrogen. In this activation step, the coordinating cyclooctadiene is split off. As expected, with the subsequent pH2 introductions in these samples, the signal enhancement increased significantly. This is already known from reactions in methanol. The observations from the measurements in xylene were unexpected. Initially, no signal amplifications were detectable here. After adding 500uL of CH3OH (to the xylene solution) no reaction was also measurable. Only after several hours a clear signal enhancement of the 19F signal could be detected (Fig.2). The detected negative phase of the increased 19F signal is also a special feature, since in pure CH3OH a positive signal enhancement can be detected in the case of 3-fluoropyridine. This is worth mentioning because so far, the negative 19F signal enhancement could only be detected in our studies with the Crabtree catalyst.
Conclusion: This study shows how much the choice of solvent influences the SABRE reaction. Not only the signal enhancement, but also the phase are changed by additives. The fact that the phase of the enhanced signal is different for the same catalyst and molecule shows that the solvent has an influence on the coupling system during polarization transfer.
