Low-field thermal mixing in [1-¹³C] pyruvic acid for brute-force hyperpolarization

Abstract

We detail the process of low-field thermal mixing (LFTM) between (1)H and (13)C nuclei in neat [1-(13)C] pyruvic acid at cryogenic temperatures (4-15 K). Using fast-field-cycling NMR, (1)H nuclei in the molecule were polarized at modest high field (2 T) and then equilibrated with (13)C nuclei by fast cycling (∼300-400 ms) to a low field (0-300 G) that activates thermal mixing. The (13)C NMR spectrum was recorded after fast cycling back to 2 T. The (13)C signal derives from (1)H polarization via LFTM, in which the polarized ('cold') proton bath contacts the unpolarised ('hot') (13)C bath at a field so low that Zeeman and dipolar interactions are similar-sized and fluctuations in the latter drive (1)H-(13)C equilibration. By varying mixing time (tmix) and field (Bmix), we determined field-dependent rates of polarization transfer (1/τ) and decay (1/T1m) during mixing. This defines conditions for effective mixing, as utilized in 'brute-force' hyperpolarization of low-γ nuclei like (13)C using Boltzmann polarization from nearby protons. For neat pyruvic acid, near-optimum mixing occurs for tmix∼ 100-300 ms and Bmix∼ 30-60 G. Three forms of frozen neat pyruvic acid were tested: two glassy samples, (one well-deoxygenated, the other O2-exposed) and one sample pre-treated by annealing (also well-deoxygenated). Both annealing and the presence of O2 are known to dramatically alter high-field longitudinal relaxation (T1) of (1)H and (13)C (up to 10(2)-10(3)-fold effects). Here, we found smaller, but still critical factors of ∼(2-5)× on both τ and T1m. Annealed, well-deoxygenated samples exhibit the longest time constants, e.g., τ∼ 30-70 ms and T1m∼ 1-20 s, each growing vs. Bmix. Mixing 'turns off' for Bmix > ∼100 G. That T1m≫τ is consistent with earlier success with polarization transfer from (1)H to (13)C by LFTM.

Transportable hyperpolarized metabolites

“…In this communication, capitalizing on this concept of DNP relayed by spin diffusion, we show how micro-particles can be hyperpolarized in trapped states with high polarization levels of typically P ( 13 C)>10%, and with long lifetimes at 4.2 K of typically T 1 ( 13 C)>5 h. We also show that due to the special nature of these states, the polarized sample can be removed from the DNP polarizer while preserving much of its polarization, in contrast to 13 C spins of metabolites dissolved in conventional glassy DNP samples and similar to silicon nanoparticles2526. The polarized sample can even be transported, and finally dissolved to the liquid state in a remote location.…”

“…This was demonstrated recently in the context of brute force hyperpolarization where neat [1- 13 C]pyruvic acid was thermally polarized without PAs by cooling to 2 K in a field of 14 T (refs 34, 35). Special care needs to be taken with regard to the magnetic field for sample shuttling out of the polarizer, so as to avoid excessive relaxation losses and low-field nuclear thermal mixing3637 as recently illustrated by Peat et al 26. To test the feasibility of our strategy towards transporting hyperpolarization, Fig.…”

Scalable dissolution-dynamic nuclear polarization with rapid transfer of a polarized solid

“…Bullet-DNP may also have advantages when polarizing larger samples, e.g., for clinical studies. The transfer in the solid enables a combination of DNP with low-field thermal mixing (LFTM) [20], where polarization is transferred from protons to low-γ-nuclei simply by shuttling the sample through a region of low field. Such a strategy does not suffer from the sample size limitations that exist for cross-polarization [12].…”

“…Radicals cause extremely rapid relaxation at low fields and elevated sample temperatures. Samples for brute-force hyperpolarization are therefore deoxygenated to remove any paramagnetic impurities and kept under inert atmosphere [20,21].…”

Dipolar Order Mediated <sup>1</sup>H→<sup>13</sup>C Cross-Polarization for Dissolution-Dynamic Nuclear Polarization

“…89 Y nuclei cannot be polarized easily via traditional CP experiments due to unfeasible CP matching conditions on the heteronuclear rf-channel. Other alternatives to the CP approach also exist but are theoretically less efficient, such as low magnetic field nuclear thermal mixing (Gadian et al, 2012) which relies on energy conserving mutual spin-flips in overlapping NMR lineshapes to polarize heteronuclei in solid samples (Peat et al, 2016).…”