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

Abstract

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 are 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-fold. 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.

NMR Spectroscopy and Metal Ions in Life Sciences

“…On the basis of our experimental observation, we postulated that the largest impact on the DNP efficiency arises from the reduction of the electron T 1 of the radical, which allows for more efficient “recycling“ of the DNP process . This idea has been subsequently adopted by other authors …”

Metal‐Chelated Polymer Nanodiscs for NMR Studies

“…This system coupled with recent developments in our lab to measure RDCs will yield an useful tool for fast NMR acquisition in the study of biomolecules as well as the already known application in MP research. This study also creates potential avenues to use the paramagnetic nature of the chelated polymer nanodiscs for dynamic nuclear polarization (DNP) solid‐state NMR experiments to overcome the sensitivity issues in studying membrane proteins. We expect that the reported novel polymer design would enable multi‐labeling to utilize the benefits of PRE, 19 F and DNP approaches for distance measurements on membrane proteins by solid‐state NMR spectroscopy.…”

A spin-thermodynamic approach to characterize spin dynamics in TEMPO-based samples for dissolution DNP at 7 T field

“…Recent results show that the spin dynamics in such samples depend heavily on composition and measurement conditions, with the change in static magnetic field playing a major role [28,39,[41][42][43][44][45][46][47][48]. But to the best of our knowledge none of the analytical models is able to predict optimum sample compositions useful in applications.…”