Peat, D.T., et al., Low-field thermal mixing in [1-(13)C] pyruvic acid for brute-force hyperpolarization. Phys Chem Chem Phys, 2016. 18(28): p. 19173-82.
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 ( approximately 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/tau) and decay (1/T1m) during mixing. This defines conditions for effective mixing, as utilized in ‘brute-force’ hyperpolarization of low-gamma nuclei like (13)C using Boltzmann polarization from nearby protons. For neat pyruvic acid, near-optimum mixing occurs for tmix approximately 100-300 ms and Bmix approximately 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 approximately (2-5)x on both tau and T1m. Annealed, well-deoxygenated samples exhibit the longest time constants, e.g., tau approximately 30-70 ms and T1m approximately 1-20 s, each growing vs. Bmix. Mixing ‘turns off’ for Bmix > approximately 100 G. That T1m>>tau is consistent with earlier success with polarization transfer from (1)H to (13)C by LFTM.