Transition Metal Doping Reveals Link between Electron T₁ Reduction and ¹³C Dynamic Nuclear Polarization Efficiency

Optimal efficiency of dissolution dynamic nuclear polarization (DNP) is essential to provide the required high sensitivity enhancements for in vitro and in vivo hyperpolarized ¹³C nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI). At the nexus of the DNP process are the free electrons, which provide the high spin alignment that is transferred to the nuclear spins. Without changing DNP instrumental conditions, one way to improve ¹³C DNP efficiency is by adding trace amounts of paramagnetic additives such as lanthanide (e.g., Gd³⁺, Ho³⁺, Dy³⁺, Tb³⁺) complexes to the DNP sample, which has been observed to increase solid-state ¹³C DNP signals by 100-250%. Herein, we have investigated the effects of paramagnetic transition metal complex R-NOTA (R = Mn²⁺, Cu²⁺, Co²⁺) doping on the efficiency of ¹³C DNP using trityl OX063 as the polarizing agent. Our DNP results at 3.35 T and 1.2 K show that doping the ¹³C sample with 3 mM Mn²⁺-NOTA led to a substantial improvement of the solid-state ¹³C DNP signal by a factor of nearly 3. However, the other transition metal complexes Cu²⁺-NOTA and Co²⁺-NOTA complexes, despite their paramagnetic nature, had essentially no impact on solid-state ¹³C DNP enhancement. W-band electron paramagnetic resonance (EPR) measurements reveal that the trityl OX063 electron T₁ was significantly reduced in Mn²⁺-doped samples but not in Cu²⁺- and Co²⁺-doped DNP samples. This work demonstrates, for the first time, that not all paramagnetic additives are beneficial to DNP. In particular, our work provides a direct evidence that electron T₁ reduction of the polarizing agent by a paramagnetic additive is an essential requirement for the improvement seen in solid-state ¹³C DNP signal.