bcTol: a highly water-soluble biradical for efficient dynamic nuclear polarization of biomolecules

Jagtap, Anil P.; Geiger, Michel-Andreas; Stöppler, Daniel; Orwick‐Rydmark, Marcella; Oschkinat, Hartmut; Sigurdsson, Snorri Th.

doi:10.1039/c6cc01813k

Cited by 58 publications

(74 citation statements)

References 38 publications

(5 reference statements)

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“…Synthesis of bcTol‐M started with the protected spirocyclohexanolyl nitroxide 1 , which was used for the synthesis of bcTol . Reductive amination of 1 with methylamine gave amino methyl derivative 2 in good yields.…”

Section: Resultsmentioning

confidence: 99%

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

Geiger

Jagtap

Kaushik

et al. 2018

Chemistry A European J

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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.

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Section: Resultsmentioning

confidence: 99%

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

Geiger

Jagtap

Kaushik

et al. 2018

Chemistry A European J

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“…Enhancements, typically defined as the intensity of the NMR signal with microwaves on vs. microwaves off (I on /I off ), can practically range from minimal (i.e., no enhancement) to 515 on model compounds [41,45,46]. Counteracting this enhancement are detrimental effects of the sample conditions typically used for the DNP experiment, and thus this definition of enhancement is not a complete figure of merit.…”

Section: Introduction: Dnp Broadens the Horizons Of Solid State Nmrmentioning

confidence: 99%

New NMR tools for protein structure and function: Spin tags for dynamic nuclear polarization solid state NMR

Rogawski

McDermott

2017

Archives of Biochemistry and Biophysics

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Magic angle spinning solid state NMR studies of biological macromolecules [1–3] have enabled exciting studies of membrane proteins [4,5], amyloid fibrils [6], viruses, and large macromolecular assemblies [7]. Dynamic nuclear polarization (DNP) provides a means to enhance detection sensitivity for NMR, particularly for solid state NMR, with many recent biological applications and considerable contemporary efforts towards elaboration and optimization of the DNP experiment. This review explores precedents and innovations in biological DNP experiments, especially highlighting novel chemical biology approaches to introduce the radicals that serve as a source of polarization in DNP experiments.

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“…Generally,a ny condition in which the g yy tensorc omponents of both radicals are perpendicular to one anotheri s expectedt oh ave near-optimal DNP performance. [30,33,34] Notably,i th as also been demonstrated that the TEKPola nd AMUPol biradicalsa re capable of yieldinge nhancement factors of upt o5 15 and 363 at 100 K, respectively,i n standard solutions that are doped with sapphire crystals. Lastly, the calculations showed that the electron T 1e value should be near 500 mst oy ield optimal performance.…”

Section: Introductionmentioning

confidence: 96%

In Silico Design of DNP Polarizing Agents: Can Current Dinitroxides Be Improved?

2017

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Numerical calculations of enhancement factors offered by dynamic nuclear polarization in solids under magic angle spinning (DNP-MAS) were performed to determine the optimal EPR parameters for a dinitroxide polarizing agent. We found that the DNP performance of a biradical is more tolerant to the relative orientation of the two nitroxide moieties than previously thought. Generally, any condition in which the g tensor components of both radicals are perpendicular to one another is expected to have near-optimal DNP performance. Our results highlight the important role of the exchange coupling, which can lessen the sensitivity of DNP performance to the inter-radical distance, but also lead to lower enhancements when the number of atoms in the linker becomes less than three. Lastly, the calculations showed that the electron T value should be near 500 μs to yield optimal performance. Importantly, the newest polarizing agents already feature all of the qualities of the optimal polarizing agent, leaving little room for further improvement. Further research into DNP polarizing agents should then target non-nitroxide radicals, as well as improvements in sample formulations to advance high-temperature DNP and limit quenching and reactivity.

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bcTol: a highly water-soluble biradical for efficient dynamic nuclear polarization of biomolecules

Cited by 58 publications

References 38 publications

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

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

New NMR tools for protein structure and function: Spin tags for dynamic nuclear polarization solid state NMR

In Silico Design of DNP Polarizing Agents: Can Current Dinitroxides Be Improved?

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