Efficiency of Water‐Soluble Nitroxide Biradicals for Dynamic Nuclear Polarization in Rotating Solids at 9.4 T: bcTol‐M and cyolyl‐TOTAPOL as New Polarizing Agents

Abstract

Nitroxide biradicals are very efficient polarizing agents in magic angle spinning (MAS) cross effect (CE) dynamic nuclear polarization (DNP) nuclear magnetic resonance (NMR). Many recently synthesized, new radicals show superior DNP-efficiency in organic solvents but suffer from insufficient solubility in water or glycerol/water for biological applications. We report DNP efficiencies for two new radicals, the water-soluble bcTol-M and cyolyl-TOTAPOL, and include a comparison with three known biradicals, TOTAPOL, bcTol, and AMUPol. They differ by linker groups, featuring either a 3-aminopropane-1,2-diol or a urea tether, or by the structure of the alkyl substituents that flank the nitroxide groups. For evaluating their performances, we measured both signal enhancements ϵ and DNP-enhanced sensitivity κ, and compared the results to electron spin relaxation data recorded at the same magnetic field strength (9.4 T). In our study, differences in DNP efficiency correlate with changes in the nuclear polarization dynamics rather than electron relaxation. The ratios of their individual ϵ and κ differ by up to 20 %, which is explained by starkly different nuclear polarization build-up rates. For the radicals compared here empirically, using proline standard solutions, the new radical bcTol-M performs best while being most soluble in water/glycerol mixtures.

Computationally Assisted Design of Polarizing Agents for Dynamic Nuclear Polarization Enhanced NMR: The AsymPol Family

“… 6 Such biradicals show much improved performance because they fulfill the requirement of having two strongly coupled electron spins for MAS-DNP via the cross-effect mechanism (CE). 7 − 9 Considerable effort has been directed toward further improvement of such biradical polarizing agents by adjusting their water solubility, 10 − 12 increasing their molecular weight, 13 using rigid linkers, 14 and replacing methyl groups that are adjacent to the nitroxides; 13 , 15 , 16 the water solubility allows for compatibility with biomolecular studies, whereas the other chemical modifications were performed to improve the properties of the electron spins (e.g., relaxation times). As such, various state-of-the-art designer polarizing agents for MAS-DNP experiments have been produced allowing high performance even at low concentration.…”

TinyPols: a family of water-soluble binitroxides tailored for dynamic nuclear polarization enhanced NMR spectroscopy at 18.8 and 21.1 T

“…Since then, binitroxides have been extensively studied at 9.4 T and their structure improved by adjusting the length and rigidity of the organic tether to optimize the electron-electron (e-e) coupling and/or the relative orientation of their g-tensors, or by ne tuning their functional groups to modulate their electron relaxation times and/or their solubility. [11][12][13][14][15][16][17][18][19] This has led to very efficient polarizing agents such as AMUPol 12 or TEKPol 17 that provide enhancement factors of over 250 at 9.4 T and 100 K in variety of glassy matrices. Most applications of DNP MAS NMR are undertaken using these biradicals that remain today the gold standard polarizing agents for hyperpolarized solid-state NMR spectroscopy.…”

Conformation of bis-nitroxide polarizing agents by multi-frequency EPR spectroscopy

“…For CE DNP, a multitude of bis-nitroxide radicals have been synthesized and their DNP performance has been investigated. [11][12][13][14][15][16][17][18][19][20][21][22] Clearly much progress has been made and 1 H NMR signal enhancement factors 4200 have become the standard at 400 MHz/263 GHz.…”