Work

Effects of Deuteration of 13C-Enriched Phospholactate on Efficiency of Parahydrogen-Induced Polarization by Magnetic Field Cycling

Year: 2018

Type: article

Abstract: We report herein a large-scale (>10 g) synthesis of isotopically enriched 1- 13 C-phosphoenolpyruvate and 1- 13 C-phosphoenolpyruvate- d 2 for application in hyperpolarized imaging technology. 1- 13 C-Phosphoenolpyruvate- d 2 was synthesized with 57% overall yield (over two steps), and >98% 2 H isotopic purity, representing an improvement over the previous report. The same outcome was achieved for 1- 13 C-phosphoenolpyruvate. These two unsaturated compounds with C═C bonds were employed for parahydrogen-induced polarization via pairwise parahydrogen addition in aqueous medium. We find that deuteration of 1- 13 C-phosphoenolpyruvate resulted in overall increase of 1 H T 1 of nascent hyperpolarized protons (4.30 ± 0.04 s versus 2.06 ± 0.01 s) and 1 H polarization (∼2.5% versus ∼0.7%) of the resulting hyperpolarized 1- 13 C-phospholactate. The nuclear spin polarization of nascent parahydrogen-derived protons was transferred to 1- 13 C nucleus via a magnetic field cycling procedure. The proton T 1 increase in deuterated hyperpolarized 1- 13 C-phospholactate yielded approximately 30% better 13 C polarization compared to that of nondeuterated hyperpolarized 1- 13 C-phospholactate. Analysis of T 1 relaxation revealed that deuteration of 1- 13 C-phospholactate may have resulted in approximately 3-fold worse 1 H → 13 C polarization transfer efficiency via magnetic field cycling. Since magnetic field cycling is a key polarization transfer step in the side-arm hydrogenation approach, the presented findings may guide more rational design of a broad range of 13 C hyperpolarized contrast agents for molecular imaging employing 13 C MRI. The hyperpolarized 1- 13 C-phospholactate- d 2 is of biomedical imaging relevance because it undergoes in vivo dephosphorylation and becomes 13 C hyperpolarized lactate, which as we show can be detected in the brain by 13 C hyperpolarized MRI; this feasibility demonstration has implications for future imaging of neurodegenerative diseases and dementia.

Source: The Journal of Physical Chemistry C

DOI: 10.1021/acs.jpcc.8b07365