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The effects of nitroxide structure upon Overhauser dynamic nuclear polarization efficacy at ultralow-field
Kai Buckenmaier1, Paul Fehling1, Sergey Dobrynin2, Denis Morozov2, Yulia Borozdina1, Jörn Engelmann1, Yuliya Polienko2, Yulia Khoroshunova2, Klaus Scheffler1, Goran Angelovski1, Igor Kirilyuk2
1 Max Planck Institute for Biological Cybernetics, Tübingen, Germany
2 Novosibirsk Institute of Organic Chemistry, Novosibirsk, Russian Federation
Introduction
Overhauser dynamic nuclear polarization (ODNP) is a hyperpolarization method, which transfers electron spin order to protons. In contrast to other DNP mechanisms (solid effect, cross effect, etc.), the Overhauser effect allows for the hyperpolarization of liquids and can be used for in vivo Overhauser MRI (OMRI) at ultralow-fields (< 10 mT). For OMRI usually trityl radicals or nitroxides such as carboxy-PROXYL and TEMPO in mM concentrations are used. In this study a great variety of nitroxide free radical molecules are being investigated in respect to their physical ODNP properties.
Methods
All measurements were performed with a home-made superconducting quantum interference device based field cycling ULF-MRI setup operating at B0 = 92 ± 0.8 mT and hyperpolarization field Bp = 1—10 mT. For radical characterization, the hyperpolarization field was set to 2 – 4 mT, matching an electron Larmor frequency of we = (120 ± 1) MHz. The spin probes were dissolved in PBS (Phosphate Buffered Saline) and pH adjusted to 7.3. For TEMPO a 2 mM concentration leads to the highest enhancement at a moderate HF power level P. For the sample characterization, the leakage factor f, the product of the coupling constant and the maximum saturation factor x∙smax, the maximum theoretical possible enhancement Emax and the power P1/2 needed to reach 0.5∙Emax have been determined.
Results/Discussion
More than 25 different nitroxide free radicals were synthesized and characterized. The focus was set on the interpretation of P1/2 and Emax. These are the most relevant parameters for application. It was found that P1/2 is strongly dependent on the line width of the ODNP spectrum. Additionally, 15N labelled nitroxides will have improved P1/2 over 14N counterparts since the losses from mixing of the energy levels are reduced. The neighboring substituents of the nitroxide group seem to have an important influence on the linewidth, where methyl substituents (blue circles in fig.) lead to the lowest P1/2. In our experiments, pyrrolidines showed better P1/2 than piperidines. The molecular weight has a significant influence on Emax, but not on P1/2 (see fig. A and B). This indicates a correlation between the tumbling rate and Emax. The results also suggest that polyradicals with significant spin-spin coupling exhibit too much spectral line broadening to produce a relevant ODNP enhancement.
Conclusions
The ideal nitroxide radical would be a lightweight, deuterated 15N-pyrrolidine monoradical, with neighboring methyl substituents and a narrow linewidth ODNP spectrum. Such a radical is likely to have a high maximum enhancement Emax at a low P1/2. The presented results provide a list of ODNP properties of different spin probes, which helps to investigate the functionalization of free radicals by incorporation into macro- or carrier molecules.
Acknowledgement
The synthesis of 2,2,5,5-tetraethylpyrrolidine-1-oxyls was supported by the Russian Foundation for Basic Research (grant 18-53-76003 within the framework of the ERA.Net RUS+ project ST2017-382: NanoHyperRadicals).
Disclosure
I or one of my co-authors have no financial interest or relationship to disclose regarding the subject matter of this presentation.
Figure
Emax A and P1/2 B of non-deuterated and 14N Nitroxide monoradicals over molecular weight.
