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 ¹H and ¹³C nuclei in neat [1-¹³C] pyruvic acid at cryogenic temperatures (4–15 K). Using fast-field-cycling NMR, ¹H nuclei in the molecule were polarized at modest high field (2 T) and then equilibrated with ¹³C nuclei by fast cycling (∼300–400 ms) to a low field (0–300 G) that activates thermal mixing. The ¹³C NMR spectrum was recorded after fast cycling back to 2 T. The ¹³C signal derives from ¹H polarization via LFTM, in which the polarized (‘cold’) proton bath contacts the unpolarised (‘hot’) ¹³C bath at a field so low that Zeeman and dipolar interactions are similar-sized and fluctuations in the latter drive ¹H–¹³C equilibration. By varying mixing time (t_mix) and field (B_mix), we determined field-dependent rates of polarization transfer (1/τ) and decay (1/T_1m) during mixing. This defines conditions for effective mixing, as utilized in ‘brute-force’ hyperpolarization of low-γ nuclei like ¹³C using Boltzmann polarization from nearby protons. For neat pyruvic acid, near-optimum mixing occurs for t_mix ∼ 100–300 ms and B_mix ∼ 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 ¹H and ¹³C (up to 10²–10³-fold effects). Here, we found smaller, but still critical factors of ∼(2–5)× on both τ and T_1m. Annealed, well-deoxygenated samples exhibit the longest time constants, e.g., τ ∼ 30–70 ms and T_1m ∼ 1–20 s, each growing vs. B_mix. Mixing ‘turns off’ for B_mix > ∼100 G. That T_1m ≫ τ is consistent with earlier success with polarization transfer from ¹H to ¹³C by LFTM.