Dissolution DNP NMR with solvent mixtures: Substrate concentration and radical extraction

Abstract

Dynamic nuclear polarization (DNP) followed by sudden sample dissolution, is a topic of active investigation owing to the method's unique prospects for the delivery of NMR spectra and images with unprecedented sensitivity. This experiment achieves hyperpolarization by the combined effects of electron-nuclear irradiation and cryogenic operation; the exploitation of these states occurs following a sudden melting and flushing of the resulting pellet from its original environment into a conventional, liquid-state setting. This melting and flushing usually demands using the equivalent of a few milliliters of hot solvent, a procedure which although well suited for in vivo studies leads to an excessive sample volume when considering typical applications within analytical settings. The present study explores a way of reducing the ensuing dilution of the hyperpolarized analytes, by employing a combination of immiscible liquids for performing the melting and flushing. It is shown that suitable combinations of immiscible solvents -both in terms of their heat capacities and densities-allow one to melt the targeted cryogenic pellet and dissolve the hyperpolarized analytes in a fraction of the solvent hitherto required. By tailoring the resulting volume to the needs of a conventional 5mm NMR probe, a substantial sensitivity enhancement can be added to the hyperpolarization process. An extra benefit may arise from using radicals that preferentially dissolve in the immiscible organic phase, by way of a lengthening of the relaxation time of the investigated analytes. Examples of these principles are given, and further potential extensions of this approach are discussed.

Chemistry and biochemistry of13C hyperpolarized magnetic resonance using dynamic nuclear polarization

“…Approaches to minimize the dilution of HP analytes include use of immiscible liquids for the melting and flushing of the DNP sample; this significantly reduces the amount of aqueous solvent required. 79 …”

Optimizing dissolution dynamic nuclear polarization

“…The same issue also arises during the infusion of hyperpolarized molecules into the blood stream, during the time lag before reaching the targeted organs for in vivo applications, as well as during the signal acquisition. Multiple strategies have been explored and developed in the last years for minimizing losses of polarization, such as the use of fast fluid transfer devices [19], the rapid elimination of the free radicals [20][21][22], or the storage of hyperpolarization in the form of long-lived states (LLS) [23][24][25][26][27][28].…”

Hybrid polarizing solids for pure hyperpolarized liquids through dissolution dynamic nuclear polarization

“…Relaxation losses are exacerbated by remaining paramagnetic PAs that no longer serve any function after dissolution; thus, one of the most effective ways to slow down the relaxation rate R 1 ( 13 C) and hence, prolong the lifetime of the polarization P( 13 C) is to eliminate the radicals (14). For some radicals, such as trityls, separation can be achieved by solvent extraction (15) or precipitation by a jump in pH followed by mechanical filtration through a stack of polyethylene filters (16,17). Lumata et al (18,19) have shown that precipitation can be used for 1,3 bisdiphenylene-2-phenylallyl (BDPA) and 2,2 diphenyl-1-picrylhydrazyl (DPPH).…”