Contrast Agent Mn-NOTA Enhances Dynamic Nuclear Polarization

…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.

Dynamic nuclear polarization (DNP)¹ has become a valuable tool for enhancing nuclear magnetic resonance (NMR) signals. The transfer of spin polarization from highly polarized electrons to the nuclei of the sample to improve their nuclear spin can increase the NMR signal by several orders of magnitude².

It is desirable to increase the sensitivity of NMR if the sample to be studied has nuclei with a low natural abundance, such as ¹³C. NMR sensitivity can be improved by using a larger sample, increasing the scan duration or using a higher magnetic field. However, it is preferable to use a more precise method, such as DNP. The technique has proved especially valuable for ¹³C metabolic imaging^3,4.

NMR spectroscopy is a highly desirable and useful analytical tool in both research and industry. It provides tremendous detail on the structure, dynamics, reaction state, and chemical environment of molecules. Furthermore, it can be used to either simultaneously identify and quantify the constituents of an unknown sample or to specifically detect the amount of a particular species present. In addition, NMR  does not damage the sample and so multiple measurements can be taken over time in living tissue.

As the applications of NMR become increasingly complex, the requirement to further increase the sensitivity of the technique also rises. Consequently, there has been much research into determining the optimal polarization procedure for maximizing the enhancement in NMR signal.

Nitroxides and trityls are most commonly used as the polarizing agent that provides the free electrons as their electron paramagnetic resonance (EPR) spectra makes them particularly well suited to polarizing ¹H and ¹³C, respectively, which are popular NMR target nuclei. In order to achieve even greater NMR signal enhancement, these polarizing agents have been doped with paramagnetic compounds and metal ions, such as gadolinium, manganese, and copper. Such doping is thought to effectively enhance trityl ¹³CDNP through the reduction of electron T1 of the polarizing agent⁵.

For the first time, paramagnetic transition metal complexes have recently been studied for efficiency as doping agents to enhance ¹³C DNP6. The polarizing agent, trityl OX063, was used to obtain NMR spectra of ¹³C sodium acetate in its pure state and doped with one of three paramagnetic transition metal complexes (Mn-NOTA, Cu-NOTA or Co-NOTA). Each solution was evaluated by EPR at the National High Magnetic Field Laboratory using a Bruker E680 EPR spectrometer with a TE011 cylindrical cavity.

Doping with Mn-NOTA was found to provide a three-fold increase in solid-state ¹³C DNP signal⁶. However, no such enhancement of solid-state ¹³C DNP EPR signals was observed with either Cu-NOTA or Co-NOTA.

Further evaluation of the trityl OX063 polarizing agent using W-band EPR  revealed that the electron T1 was significantly reduced in the samples doped with Mn²⁺. Despite their paramagnetic nature, the electron T1 was not reduced in the samples doped with either Cu²⁺ or Co²⁺.

This latest research demonstrated that not all paramagnetic additives are beneficial in the enhancement of DNP.  In addition, it provided the first direct evidence that electron T1 reduction of the polarizing agent is an essential requirement for enhancing solid-state ¹³C DNP signal.

References

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