{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:55:22Z","timestamp":1790564122161,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Nitroxide biradicals are efficient polarizing agents in dynamic nuclear polarization (DNP) solid-state nuclear magnetic resonance. Many recently reported radicals possess substantial DNP efficiency in organic solvents but have poor solubility in water media which is unfavorable for biological applications. In this paper, we report DNP efficiency at a high magnetic field for two water-soluble biradicals resistant to reducing media. Water solubility was achieved by obtaining the radicals in the form of quaternary ammonium salts. Parameters of hyperfine interaction and exchange interaction were quantified by EPR spectroscopy, and their influence on the DNP effect was determined. The resistance of the biradicals to strongly reducing media was characterized. High stability was achieved using tetraethyl substituents and pyrrolidine moieties.<\/jats:p>","DOI":"10.3390\/molecules28041926","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T02:02:09Z","timestamp":1676858529000},"page":"1926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["An EPR Study on Highly Stable Nitroxyl-Nitroxyl Biradicals for Dynamic Nuclear Polarization Applications at High Magnetic Fields"],"prefix":"10.3390","volume":"28","author":[{"given":"Nargiz B.","family":"Asanbaeva","sequence":"first","affiliation":[{"name":"N.N. Vorozhtsov Institute of Organic Chemistry, 9 Ac. Lavrentiev Avenue, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3486-0335","authenticated-orcid":false,"given":"Sergey A.","family":"Dobrynin","sequence":"additional","affiliation":[{"name":"N.N. Vorozhtsov Institute of Organic Chemistry, 9 Ac. Lavrentiev Avenue, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis A.","family":"Morozov","sequence":"additional","affiliation":[{"name":"N.N. Vorozhtsov Institute of Organic Chemistry, 9 Ac. Lavrentiev Avenue, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Haro-Mares","sequence":"additional","affiliation":[{"name":"TU Darmstadt, Eduard-Zintl-Institute for Inorganic and Physical Chemistry, Alarich-Weiss-Stra\u00dfe 8, 64287 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6214-2272","authenticated-orcid":false,"given":"Torsten","family":"Gutmann","sequence":"additional","affiliation":[{"name":"TU Darmstadt, Eduard-Zintl-Institute for Inorganic and Physical Chemistry, Alarich-Weiss-Stra\u00dfe 8, 64287 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1304-9762","authenticated-orcid":false,"given":"Gerd","family":"Buntkowsky","sequence":"additional","affiliation":[{"name":"TU Darmstadt, Eduard-Zintl-Institute for Inorganic and Physical Chemistry, Alarich-Weiss-Stra\u00dfe 8, 64287 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0057-383X","authenticated-orcid":false,"given":"Elena G.","family":"Bagryanskaya","sequence":"additional","affiliation":[{"name":"N.N. Vorozhtsov Institute of Organic Chemistry, 9 Ac. Lavrentiev Avenue, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,17]]},"reference":[{"key":"ref_1","first-page":"120","article-title":"Dynamic Nuclear Polarization for Sensitivity Enhancement in Modern Solid-State NMR","volume":"102\u2013103","author":"Wittmann","year":"2017","journal-title":"Prog. Nucl. Magn. Reson. Spectrosc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.arnmr.2018.12.001","article-title":"Solid-State NMR of Nanocrystals","volume":"97","author":"Gutmann","year":"2019","journal-title":"Annu. Rep. NMR Spectrosc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1146\/annurev-physchem-071119-040222","article-title":"High-Field Dynamic Nuclear Polarization","volume":"71","author":"Corzilius","year":"2020","journal-title":"Annu. Rev. Phys. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cocis.2017.11.002","article-title":"Optimal Sample Formulations for DNP SENS: The Importance of Radical-Surface Interactions","volume":"33","author":"Perras","year":"2018","journal-title":"Curr. Opin. Colloid Interface Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1080\/10587259708044551","article-title":"Preparation and Property of 2-(3\u2032,5\u2032-Di-Tert-Butylphenyl-4\u2032-Oxyl)-4,4,5,5-Tetramethyl-4,5, -Dihydro-1H-Imidazole-3-Oxide-1-Oxyl","volume":"306","author":"Ishiguro","year":"1997","journal-title":"Mol. Cryst. Liq. Cryst."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4494","DOI":"10.1002\/1521-3773(20001215)39:24<4494::AID-ANIE4494>3.0.CO;2-X","article-title":"Application of a Spin-Labeled Spin-Trap to the Detection of Nitric Oxide (NO)","volume":"39","author":"Marx","year":"2000","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.freeradbiomed.2008.04.019","article-title":"In Vivo EPR Measurement of Glutathione in Tumor-Bearing Mice Using Improved Disulfide Biradical Probe","volume":"45","author":"Roshchupkina","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11385","DOI":"10.1021\/ja061284b","article-title":"TOTAPOL: A Biradical Polarizing Agent for Dynamic Nuclear Polarization Experiments in Aqueous Media","volume":"128","author":"Song","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1002\/cbic.201600185","article-title":"Surface Binding of TOTAPOL Assists Structural Investigations of Amyloid Fibrils by Dynamic Nuclear Polarization NMR Spectroscopy","volume":"17","author":"Nagaraj","year":"2016","journal-title":"ChemBioChem"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13485","DOI":"10.1002\/chem.201801251","article-title":"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","volume":"24","author":"Geiger","year":"2018","journal-title":"Chem. A Eur. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7020","DOI":"10.1039\/C6CC01813K","article-title":"BcTol: A Highly Water-Soluble Biradical for Efficient Dynamic Nuclear Polarization of Biomolecules","volume":"52","author":"Jagtap","year":"2016","journal-title":"Chem. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5598","DOI":"10.1002\/chem.201504693","article-title":"Tailoring of Polarizing Agents in the BTurea Series for Cross-Effect Dynamic Nuclear Polarization in Aqueous Media","volume":"22","author":"Casano","year":"2016","journal-title":"Chem. A Eur. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"107150","DOI":"10.1016\/j.jmr.2022.107150","article-title":"Stability of the Nitroxide Biradical AMUPol in Intact and Lysed Mammalian Cells","volume":"336","author":"Ghosh","year":"2022","journal-title":"J. Magn. Reson."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7847","DOI":"10.1021\/acs.jpcb.2c03985","article-title":"Biradical Polarizing Agents at High Fields","volume":"126","author":"Michaelis","year":"2022","journal-title":"J. Phys. Chem. B"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1021\/jp410387e","article-title":"High Field Dynamic Nuclear Polarization NMR with Surfactant Sheltered Biradicals","volume":"118","author":"Kiesewetter","year":"2014","journal-title":"J. Phys. Chem. B"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"12790","DOI":"10.1021\/ja405813t","article-title":"Large Molecular Weight Nitroxide Biradicals Providing Efficient Dynamic Nuclear Polarization at Temperatures up to 200 K","volume":"135","author":"Zagdoun","year":"2013","journal-title":"J. Am. Chem. Soc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2810","DOI":"10.1039\/C9SC05384K","article-title":"TinyPols: A Family of Water-Soluble Binitroxides Tailored for Dynamic Nuclear Polarization Enhanced NMR Spectroscopy at 18.8 and 21.1 T","volume":"11","author":"Lund","year":"2020","journal-title":"Chem. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e202114103","DOI":"10.1002\/anie.202114103","article-title":"Highly Efficient Polarizing Agents for MAS-DNP of Proton-Dense Molecular Solids","volume":"61","author":"Harrabi","year":"2022","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11770","DOI":"10.1002\/anie.201504292","article-title":"Efficient Dynamic Nuclear Polarization at 800 MHz\/527 GHz with Trityl-Nitroxide Biradicals","volume":"54","author":"Mathies","year":"2015","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9047","DOI":"10.1021\/acs.jpcb.0c08321","article-title":"Postmodification via Thiol-Click Chemistry Yields Hydrophilic Trityl-Nitroxide Biradicals for Biomolecular High-Field Dynamic Nuclear Polarization","volume":"124","author":"Zhai","year":"2020","journal-title":"J. Phys. Chem. B"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13340","DOI":"10.1021\/jacs.8b08081","article-title":"BDPA-Nitroxide Biradicals Tailored for Efficient Dynamic Nuclear Polarization Enhanced Solid-State NMR at Magnetic Fields up to 21.1 T","volume":"140","author":"Wisser","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1021\/ol9001575","article-title":"Synthesis of a BDPA-TEMPO Biradical","volume":"11","author":"Dane","year":"2009","journal-title":"Org. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7486","DOI":"10.1002\/chem.202001084","article-title":"On the Limited Stability of BDPA Radicals","volume":"26","author":"Mandal","year":"2020","journal-title":"Chem. A Eur. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13121","DOI":"10.1039\/D0CC04920D","article-title":"Water-Soluble BDPA Radicals with Improved Persistence","volume":"56","author":"Mandal","year":"2020","journal-title":"Chem. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1039\/B919279D","article-title":"Trityl-Nitroxide Biradicals as Unique Molecular Probes for the Simultaneous Measurement of Redox Status and Oxygenation","volume":"46","author":"Liu","year":"2010","journal-title":"Chem. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7796","DOI":"10.1021\/jo1016844","article-title":"Synthesis of 14N- and 15N-Labeled Trityl-Nitroxide Biradicals with Strong Spin-Spin Interaction and Improved Sensitivity to Redox Status and Oxygen","volume":"75","author":"Liu","year":"2010","journal-title":"J. Org. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11422","DOI":"10.1021\/acs.jpcc.8b02570","article-title":"Novel Biradicals for Direct Excitation Highfield Dynamic Nuclear Polarization","volume":"122","author":"Bothe","year":"2018","journal-title":"J. Phys. Chem. C"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12758","DOI":"10.1002\/chem.202102253","article-title":"Highly Efficient Trityl-Nitroxide Biradicals for Biomolecular High-Field Dynamic Nuclear Polarization","volume":"27","author":"Cai","year":"2021","journal-title":"Chem. A Eur. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19266","DOI":"10.1021\/ja206999c","article-title":"Neurotoxin II Bound to Acetylcholine Receptors in Native Membranes Studied by Dynamic Nuclear Polarization NMR","volume":"133","author":"Linden","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jmr.2019.04.013","article-title":"Stability of Nitroxide Biradical TOTAPOL in Biological Samples","volume":"303","author":"Mccoy","year":"2019","journal-title":"J. Magn. Reson."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9118","DOI":"10.1021\/acs.joc.5b01494","article-title":"Effect of Sterical Shielding on the Redox Properties of Imidazoline and Imidazolidine Nitroxides","volume":"80","author":"Kirilyuk","year":"2015","journal-title":"J. Org. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11013","DOI":"10.1021\/jacs.8b04911","article-title":"Computationally Assisted Design of Polarizing Agents for Dynamic Nuclear Polarization Enhanced NMR: The AsymPol Family","volume":"140","author":"Jagtap","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13569","DOI":"10.1039\/D0CP02051F","article-title":"Balancing Dipolar and Exchange Coupling in Biradicals to Maximize Cross Effect Dynamic Nuclear Polarization","volume":"22","author":"Equbal","year":"2020","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1039\/C5SC02921J","article-title":"Rational Design of Dinitroxide Biradicals for Efficient Cross-Effect Dynamic Nuclear Polarization","volume":"7","author":"Kubicki","year":"2016","journal-title":"Chem. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1021\/ja210177v","article-title":"A Slowly Relaxing Rigid Biradical for Efficient Dynamic Nuclear Polarization Surface-Enhanced NMR Spectroscopy: Expeditious Characterization of Functional Group Manipulation in Hybrid Materials","volume":"134","author":"Zagdoun","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"16587","DOI":"10.1021\/jacs.0c04911","article-title":"Open and Closed Radicals: Local Geometry Around Unpaired Electrons Governs MAS DNP Performance","volume":"142","author":"Stevanato","year":"2020","journal-title":"J. Am. Chem. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"144203","DOI":"10.1063\/5.0064342","article-title":"The Effects of Nitroxide Structure upon 1H Overhauser Dynamic Nuclear Polarization Efficacy at Ultralow-Field","volume":"155","author":"Fehling","year":"2021","journal-title":"J. Chem. Phys."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Asanbaeva, N.B., Gurskaya, L.Y., Polienko, Y.F., Rybalova, T.V., Kazantsev, M.S., Dmitriev, A.A., Gritsan, N.P., Haro-Mares, N., Gutmann, T., and Buntkowsky, G. (2022). Effects of Spiro-Cyclohexane Substitution of Nitroxyl Biradicals on Dynamic Nuclear Polarization. Molecules, 27.","DOI":"10.3390\/molecules27103252"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5896","DOI":"10.1021\/ja00171a049","article-title":"Nuclear Overhauser Effect in Solids","volume":"112","author":"White","year":"1990","journal-title":"J. Am. Chem. Soc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"22948","DOI":"10.1021\/acs.jpcc.7b07965","article-title":"Unusual Local Molecular Motions in the Solid State Detected by Dynamic Nuclear Polarization Enhanced NMR Spectroscopy","volume":"121","author":"Hoffmann","year":"2017","journal-title":"J. Phys. Chem. C"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jmr.2016.02.014","article-title":"Room-Temperature Electron Spin Relaxation of Nitroxides Immobilized in Trehalose: Effect of Substituents Adjacent to NO-Group","volume":"266","author":"Kuzhelev","year":"2016","journal-title":"J. Magn. Reson."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5392","DOI":"10.1021\/acs.joc.8b00085","article-title":"Synthesis of 3,4-Bis(Hydroxymethyl)-2,2,5,5-Tetraethylpyrrolidin-1-Oxyl via 1,3-Dipolar Cycloaddition of Azomethine Ylide to Activated Alkene","volume":"83","author":"Dobrynin","year":"2018","journal-title":"J. Org. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5322","DOI":"10.1021\/ol302506f","article-title":"Synthesis and Reduction Kinetics of Sterically Shielded Pyrrolidine Nitroxides","volume":"14","author":"Paletta","year":"2012","journal-title":"Org. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ovcherenko, S.S., Chinak, O.A., Chechushkov, A.V., Dobrynin, S.A., Kirilyuk, I.A., Krumkacheva, O.A., Richter, V.A., and Bagryanskaya, E.G. (2021). Uptake of Cell-Penetrating Peptide RL2 by Human Lung Cancer Cells: Monitoring by Electron Paramagnetic Resonance and Confocal Laser Scanning Microscopy. Molecules, 26.","DOI":"10.3390\/molecules26185442"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.freeradbiomed.2006.11.007","article-title":"Reversible Reduction of Nitroxides to Hydroxylamines: Roles for Ascorbate and Glutathione","volume":"42","author":"Bobko","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jmr.2005.08.013","article-title":"EasySpin, a Comprehensive Software Package for Spectral Simulation and Analysis in EPR","volume":"178","author":"Stoll","year":"2006","journal-title":"J. Magn. Reson."},{"key":"ref_47","first-page":"128","article-title":"Suppression of Signals from the Probe in Bloch Decay Spectra","volume":"80","author":"Cory","year":"1988","journal-title":"J. Magn. Reson."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jmr.2010.12.011","article-title":"Straightforward, Effective Calibration of SPINAL-64 Decoupling Results in the Enhancement of Sensitivity and Resolution of Biomolecular Solid-State NMR","volume":"209","author":"Comellas","year":"2011","journal-title":"J. Magn. Reson."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5145","DOI":"10.1021\/acs.jpcc.9b10504","article-title":"Direct and Indirect Dynamic Nuclear Polarization Transfer Observed in Mesoporous Materials Impregnated with Nonionic Surfactant Solutions of Polar Polarizing Agents","volume":"124","author":"Hoffmann","year":"2020","journal-title":"J. Phys. Chem. C."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1926\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:39:37Z","timestamp":1760121577000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1926"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,17]]},"references-count":49,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["molecules28041926"],"URL":"https:\/\/doi.org\/10.3390\/molecules28041926","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,17]]}}}