The effects of nitroxide structure upon 1H Overhauser dynamic nuclear polarization efficacy at ultralow-field

Abstract

The efficacy in 1H Overhauser dynamic nuclear polarization in liquids at ultralow magnetic field (ULF, B0 = 92 ± 0.8 µT) and polarization field ( B p = 1–10 mT) was studied for a broad variety of 26 different spin probes. Among others, piperidine, pyrrolidine, and pyrroline radicals specifically synthesized for this study, along with some well-established commercially available nitroxides, were investigated. Isotope-substituted variants, some sterically shielded reduction-resistant nitroxides, and some biradicals were included in the measurements. The maximal achievable enhancement, Emax, and the radio frequency power, P1/2, needed for reaching Emax/2 were measured. Physico-chemical features such as molecular weight, spectral linewidth, heterocyclic structure, different types of substituents, deuteration, and 15N-labeling as well as the difference between monoradicals and biradicals were investigated. For the unmodified nitroxide radicals, the Emax values correlate with the molecular weight. The P1/2 values correlate with the spectral linewidth and are additionally influenced by the type of substituents neighboring the nitroxide group. The nitroxide biradicals with high intramolecular spin–spin coupling show low performance. Nitroxides enriched with 15N and/or 2H afford significantly higher | Emax| and require lower power to do so, compared to their unmodified counterparts containing at natural abundance predominantly 14N and 1H. The results allow for a correlation of chemical features with physical hyperpolarization-related properties and indicate that small nitroxides with narrow spectral lines have clear advantages for the use in Overhauser dynamic nuclear polarization experiments. Perdeuteration and 15N-labeling can be used to additionally boost the spin probe performance.

Contrast Agents Based on Human Serum Albumin and Nitroxides for 1H-MRI and Overhauser-Enhanced MRI

“…The Overhauser effect relies on incoherent electron-nuclear cross-relaxation mediated by dipole, scalar, or isotropic hyperfine interactions [14]. Unlike thermal mixing or the solid or cross effect, the Overhauser effect allows the hyperpolarization of liquids at room temperature [46]. This unique advantage allows for continuous in situ, ex vivo, or even in vivo hyperpolarization of the sample itself, eliminating the need for a hyperpolarized bolus.…”

“…For this reason, in vivo OMRI is generally performed in the low field range, with the optimal field strength depending on the sample geometry and the specific absorption rate (SAR), which must be considered to prevent sample heating [44,52,53]. Nev-ertheless, in vivo experiments on small animals have been performed using OMRI [46,48]. The success of OMRI depends on the presence of special hyperpolarizing contrast agents (HCAs) that facilitate the transfer of polarization from free electrons, such as free radicals, to nuclear spins, such as water protons, thereby enhancing the MRI signal [14,46].…”

“…Nev-ertheless, in vivo experiments on small animals have been performed using OMRI [46,48]. The success of OMRI depends on the presence of special hyperpolarizing contrast agents (HCAs) that facilitate the transfer of polarization from free electrons, such as free radicals, to nuclear spins, such as water protons, thereby enhancing the MRI signal [14,46]. It is noteworthy that this method is not limited to protons, as the hyperpolarization of other MR-active nuclei, such as 13 C, is also possible [54].…”

Solid-Effect Dynamic Nuclear Polarization in Viscous Liquids at 9.4 T Using Narrow-Line Polarizing Agents

“…In general, these mechanisms work best at a sample temperature of ≤100 K and can give large signal enhancements of ≥100 in the presence of carefully selected polarizing agents. , In liquids, only the OE mechanism is active, which requires the time-dependent interaction between electrons and nuclei on a time scale comparable with the reciprocal of the electron Larmor frequency (1/ω e ). For this reason, the liquid-state OE is most effective at low magnetic field strength. − Nonetheless, it has been recently shown that the OE can yield significant 13 C (ε ≥ 600) and 31 P (ε ≥ 160) signal enhancements at magnetic fields of 9.4 and 14 T, respectively.…”

Origin of Long-Range Hyperfine Couplings in the EPR Spectra of 2,2,5,5-Tetraethylpyrrolidine-1-oxyls

“…Complicated hyperfine structure and line broadening in the EPR spectra of sterically shielded nitroxides makes them inefficient in EPRI and OMRI applications, where radicals with a minimal number of narrow lines are required for better resolution and enhancement. − Broadened spectral lines can also hamper analysis of molecular dynamics using spin labeling and EPR . A better understanding of the factors affecting the hyperfine structure in the EPR spectra of sterically shielded nitroxides could help in the molecular design of better structures.…”