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Current Organic Chemistry

Editor-in-Chief

ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

Review Article

Synthesis and Application of Stable Nitroxide Free Radicals Fused with Carbocycles and Heterocycles

Author(s): Balázs Bognár, Györgyi Úr, Cecília Sár, Olga H. Hankovszky, Kálmán Hideg and Tamás Kálai*

Volume 23, Issue 4, 2019

Page: [480 - 501] Pages: 22

DOI: 10.2174/1385272823666190318163321

Price: $65

Abstract

Stable nitroxide free radicals have traditionally been associated with 2,2,6,6- tetramethylpiperidine-1-oxyl (TEMPO) or its 4-substituted derivatives as relatively inexpensive and readily accessible compounds with limited possibilities for further chemical modification. Over the past two decades, there has been a resurgence of interest in stable free radicals with proper functionalization tuned for various applications. The objective of this review is to present recent results with synthetic methodologies to achieve stable nitroxide free radicals fused with aromatic carbocycles and heterocycles. There are two main approaches for accessing stable nitroxide free radicals fused with arenes, e.g., isoindoline- like nitroxides: further functionalization and oxidation of phthalimide or inventive functionalization of pyrroline nitroxide key compounds. The latter also offers the constructions of versatile heterocyclic scaffolds (furan, pyrrole, thiophene, 1,2-thiazole, selenophene, pyrazole, pyrimidine, pyridine, pyridazine, 1,5-benzothiazepine) that are fused with pyrroline or tetrahydropyridine nitroxide rings. The possible applications of these new stable nitroxide free radicals, such as covalent spin labels and noncovalent spin probes of proteins and nucleic acids, profluorescent probes, building blocks for construction of dual active drugs and electroactive materials, and substances for controlled free radical polymerization, are discussed.

Keywords: Antioxidants, C-C bond formation, carbocycles, heterocycles, nitroxide free radicals, Pd-catalyzed cross-coupling, spin-labels.

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[1]
(a)Rhodes, J.C. Toxicology of the human environment; Taylor and Francis, 2000.
(b)Sosnovsky, G.; Gnewuch, C.T.; Jawdosiuk, M. Solar-Energy-Absorbing Substances and Oxidative Stress and Inflammatory Diseases; Cambridge Scholars Publishing: Newcastle upon Tyne, 2017.
(c)Chatgilialoglu, C.; Studer, A. Encyclopedia of Radicals in Chemistry, Biology and Materials, 1st ed; Wiley: New York, 2012.
(d)Halliwell, B.; Gutteridge, J.M.C. Free Radicals in Biology and Medicine, 5th ed; Oxford University Press: Oxford, 2015.
[2]
Hick, R. Stable Radicals; Wiley: Chichester, 2010.
[3]
(a)Likhtenshtein, G.I.; Yamauchi, J.; Nakatsui, S.; Smirnov, A.I.; Tamura, R. Nitroxides; Wiley-VCH: Weinheim, 2008.
(b)Rosantsev, E.G. Free Nitroxide Radicals; Plenum Press: New York, 1970.
[4]
(a)Berliner, L.J. In Nitroxides - Theory, experiment and applications; Kokorin, A.I., Ed.; Intech, 2012, pp. 3-24.
(b) Altenbach, C.; Lopez, C.J.; Hideg, K.; Hubbell, W.L. Exploring structure, dynamics, and topology of nitroxide spin-labeled proteins using continuous-wave electron paramagnetic resonance spectroscopy. Methods Enzymol., 2015, 564, 59-100.
(c) Haugland, M.M.; Anderson, E.A.; Lovett, J.E. Tuning the properties of nitroxide spin labels for use in electron paramagnetic resonance spectroscopy through chemical modification of the nitroxide framework Electron. Paramagn Reson, 2017, 25, 1-34.
(d) Bordignon, E.; Bleicken, S. New limits of sesivity of site-directed spin labeling electron paramagnetic resonance for membrane proteins. BBA-Biomembranes, 2018, 1860, 841-853.
(e) Haughland, M.M.; Lovett, J.E.; Anderson, A.E. Advances in the synthesis of nitroxide radicals for use in biomolecule spin labeling. Chem. Soc. Rev., 2018, 147, 668-680.
[5]
(a) Tebben, L.; Studer, A. Nitroxides: Applications in synthesis and in polymer chemistry. Angew. Chem. Int. Ed., 2011, 50, 5034-5068.
(b) Wertz, S.; Studer, A. Nitroxide-catalyzed transition-metal-free aerobic oxidation processes. Green Chem., 2013, 15, 3116-3134.
(c) Hansen, K.A. Blinco, J.P. Nitroxide radical polymers – a versatile material class for high-tech applications. Polym. Chem., 2018, 9, 1479-1516.
[6]
(a) Ratera, I.; Veciana, J. Playing with organic radicals as building blocks for functional molecular materials. J. Chem. Soc. Rev, 2012, 41, 303-349.
(b) Kumar, S.; Kumar, Y.; Keshri, K.S.; Mukhopadhyay, P. Recent advances in organic radicals and their magnetism. Magnetochemistry, 2016, 2, 42-77.
[7]
(a) Alexander, S-A.; Schiesser, C.H. Heteroorganic molecules and bacterial biofilms: controlling biodeterioration of cultural heritage. ARKIVOC, 2017, (part ii), 180-222.
(b) Alexander, S-A.; Kyi, C.; Schiesser, C.H. Nitroxides as anti-biofim compounds for the treatment of Pseudonomas aeruginosa and mixed cultrure biofilms. Org. Biomol. Chem., 2015, 13, 4751-4759.
[8]
(a) Soule, B.P.; Hyodo, F.; Matsumoto, K.; Simone, N.L.; Cook, J.A.; Krishna, M.C.; Mitchell, J.B. The chemistry and biology of nitroxide compounds. Free Radic. Biol. Med., 2007, 42, 1632-1650.
(b) Goldstein, S.; Samuni, A.; Hideg, K.; Merényi, G. Structure-Activity Relationship of Cyclic Nitroxides as SOD Mimics and Scavengers of Nitrogen Dioxide and Carbonate Radicals. J. Phys. Chem. A, 2006, 110, 3679-3685.
[9]
(a) Prescott, C.; Bottle, S.E. Biological relevance of free radicals and nitroxides. Cell Biochem. Biophys., 2017, 75, 227-240.
(b) Grigor’ev, I.A.; Tkacheva, N.I.; Morozov, S.V. Conjugates of natural compounds with nitroxyl radicals as a basis for creation of pharmacological agents of new generation. Curr. Med. Chem., 2014, 21, 2839-2852.
(c) Soule, B.P.; Hyodo, F.; Matsumoto, K.I.; Simone, N.L.; Cook, J.A.; Krishna, M.C.; Mitchell, J.B. Therapeutic and clinical application of nitroxide compounds. Antioxid. Redox Signal., 2007, 9, 1731-1743.
[10]
(a) Kálai, T.; Kuppusamy, M.L.; Balog, M.; Selvendiran, K.; Rivera, K.B.; Kuppusamy, P.; Hideg, K. Synthesis of N-substituted 3,5-bis(arylidene)-4-piperidones with high antitumor and antioxidant activity. J. Med. Chem., 2011, 54, 5414-5421.
(b) Bognár, B.; Kuppusamy, M.L.; Madan, E.; Kálai, T.; Balog, M.; Jekő, J.; Kuppusamy, P.; Hideg, K. Synthesis and biological evaluation of curcumin-nitroxide-based molecular hybrids as antioxidant and anti-proliferative agents. Med. Chem., 2017, 13, 761-772.
(c) Marston, L.W.; Rouault, T.A.; Mitchell, J.; Murali, K.C. Nitroxide therapy for the treatment of von Hippel-Lindau disease (vhl) and renal clear cell carcinoma (rcc). U.S. Patent 8853277, October 7, 2014.
(d) Lewandowski, M.; Gwozdzinski, K. Nitroxides as antioxidants and anticancer drugs. Int. J. Mol. Sci., 2017, 18, 2490.
[11]
(a) Edeleva, M.V.; Marque, S.; Bagryanskaya, E.G. Imidazoline and imidazolidine nitroxides as controlling agents in nitroxide-mediated pseudoliving radical polymerization. Russ. Chem. Rev., 2018, 87, 328-349.
(b) Gigmes, D., Ed.; Nitroxide mediated polymerization: from fundamentals to applications in materials science; RSC Publishing: Cambridge, 2015.
(c) Nicolas, J. Guillaneuf, Y.; Lefay, C. Bertin, D. Gigmes, D.; Charleux, B. Nitroxide-mediated polymerization. Prog. Polym. Sci., 2013, 38, 63-235.
(d) Maric, M. Application of nitroxide mediated polymerization in different monomer systems. Curr. Org. Chem., 2018, 22, 1264-1284.
[12]
Winsberg, J.; Hagemann, T.; Janoschka, T.; Hager, M.D.; Schubert, U.S. Redox-flow batteries: From metals to organic redox-active materials. Angew. Chem. Int. Ed., 2017, 56, 686-711.
[13]
(a) Lussini, C.V.; Colwell, J.M.; Fairfull-Smith, K.E.; Bottle, S.E. Profluorescent nitroxide sensors for monitoring photo-induced degradation in polymer films. Sens. Actuators B., 2017, 241, 199-209.
(b) Green, S.A.; Simpson, D.J.; Zhou, G.; Ho, P.S.; Blough, N.V. Intramolecular quenching of excited singlet states by stable nitroxyl radicals. J. Am. Chem. Soc., 1990, 112, 7337-7346.
(c) Bognár, B.; Jekő, J.; Kálai, T.; Hideg, K. Synthesis of redox sensitive dyes based on combination of long wavelength emitting fluorophores and nitroxides. Dyes Pigments, 2010, 87, 218-224.
[14]
(a) Matsumoto, K. Development of magnetic resonance-based functional imaging: the past, the present, and the future. J. Pharmaceutical Soc. Jpn, 2016, 136, 1075-1080.
(b) Hilt, S.; Tang, T.; Walton, J.H.; Budamagunta, M.; Maetawa, I.; Kálai, T.; Hideg, K.; Singh, V.; Wulff, H.; Gong, Q.; Jin, L-W.; Loie, A.; Voss, J.C. A metal-free method for producing MRI contrast at amyloid-ß. J. Alzheimers Dis., 2017, 55, 1667-1681.
[15]
(a) Wang, X.; Emoto, M.; Miyake, S.; Itto, K.; Xu, S.; Fujii, H.; Hirata, H.; Arimoto, H. Novel blood–brain barrier-permeable spin probe for in vivo electron paramagnetic resonance imaging. Bioorg. Med. Chem. Lett., 2016, 26, 4947-4949.
(b) Yan, G.P.; Peng, L.; Jian, S.Q.; Li, L.; Bottle, S.E. Spin probes for electron paramagnetic resonance imaging. Chin. Sci. Bull., 2008, 53, 3777-3789.
(c) Khramtsov, V.V.; Bobko, A.A.; Tseytlin, M.; Driesschaert, B. Exchange phenomena in the electron paramagnetic resonance spectra of the nitroxyl and trityl radicals: Multifunctional spectroscopy and imaging of local chemical microenvironment. Anal. Chem., 2017, 89, 4758-477.
[16]
(a) Georgieva, E.R. Nanoscale lipid membrane mimetics in spin-labeling and electron paramagnetic resonance spectroscopy studies of protein structure and function. Nanotechnol. Rev., 2017, 6, 75-92.
(b) Jescke, G. Conformational dynamics and distribution of nitroxide spin labels. Prog. Nuclear Res. Spectr, 2013, 72, 42-60.
(c) Guzzi, R.; Bartucci, R. Electron spin resonance of spin-labeled lipid assemblies and proteins. Arch. Biochem. Biophys., 2015, 580, 102-111.
(d) Mezzina, E.; Manoni, R.; Romano, F.; Lucarini, M. Spin-labeling of Host-Guest Assemblies with Nitroxide Radicals. Asian J. Org. Chem., 2015, 4, 296-310.
(e) Bagryanskaya, E.G.; Marque, S.R.A. Nitroxides in host-guest chemistry: 2010-2016. Electron. Paramagnetic Reson., 2017, 25, 180-235.
(f) Fielding, A.J.; Concilio, G.M.; Heaven, G.; Hollas, M.A. New developments in spin labels for pulsed dipolar EPR. Molecules, 2014, 19, 16998-17025.
(g) Böde, E.B.; Valera, S. Strategies for the synthesis of yardsticks and abaci for nanometre distance measurements by pulsed EPR. Molecules, 2014, 19, 20227-20256.
(h) Blinco, J.P.; Fairfull-Smith, K.E.; Morrow, N.J.; Bottle, S.E. Profluorescent nitroxides as sensitive probes of oxidative change and free radical reactions. Aust. J. Chem., 2011, 64, 373-389.
(i)Brick, M.E. Chemistry of persistent free bi-and polyradicals. Heterocycles, 1995, 41, 2827-2873.
(j) Shelke, S.A.; Sigurdsson, S.T. Site–directed spin labeling for EPR studies of nucleic acids.Modified Nucleic Acids; Nakatani, A.; Tor, Y., Eds.; Springer, 2016, pp. 159-187.
(k)Ouari, O.; Bardelang, D. Nitroxide radicals with cucurbit[n]urils and other cavitands. Isr. J. Chem., 2018, 58, 1-15.
(l)Kalyanaraman, B.; Cheng, G.; Hardy, M.; Ouari, O.; Lopez, M.; Joseph, J.; Zielonka, J.; Dwinell, M.B. A review of the basics of mitochondrial bioenergetics, metabolism, and related signaling pathways in cancer cells: Therapeutic targeting of tumor mitochondria with lipophilic cationic compounds. Redox Biol., 2018, 14, 316-327.
(m)Bonetta, R. Potential therapeutic applications of MnSODs and SOD-Mimetics. Chem. Eur. J.,, 2018, 24, 5032-5041.
(n)Oliveira, C.; Benfeito, S.; Fernandes, C.; Cagide, F.; Silva, T. Borges. F. NO and HNO donors, nitrones, and nitroxides: past, present, future. Med. Res. Rev., 2018, 38, 1159-1187.
(o)Magdesieva, T.V.; Levitiskiy, O.A. Molecular design of stable diarylnitroxides. Russ. Chem. Rev., 2018, 87, 707-725.
[17]
(a) Quin, P.Z.; Warnacke, K. Electron paramagnetic resonance investigations of biological systems by using spin labels, spin probes, and intrinsic metal ions. Methods Enzymol., 2015, 563, 3-624.
(b) Smirnov, A.I.; Berliner, L. Nitroxide Radicals: Synthesis and functional Bio/Nanomaterials-an introduction. J. Cell. Biochem. Biophys, 2017, 75, 149-150.
[18]
(a)Volodarsky, L.B.; Reznikov, V.A.; Ovcharenko, V.I. Synthetic Chemistry of Stable Nitroxides; CRC press: Boca Raton, 1993.
(b)Rowen, S. Concepts and Applied Principles of Nitroxides; NY Research Press: New York, 2015.
(c)Likhtenshtein, G. Electron Spin Interactions in Chemistry and Biology; Springer: New York, 2016.
(d)Zhdanov, R.I. Bioactive Spin Labels; Springer: Berlin, 1992.
(e)Chechik, V. Carter, E.; Murphy, D. Electron Paramagnetic Resonance; Oxford University Press: Oxford, 2015.
[19]
(a) Rozantsev, E.G.; Neiman, M.B. Organic radical reactions involving no free valence. Tetrahedron, 1964, 20, 131-137.
(b) Rozantzev, E.G.; Krinitzkaya, L.A. Free nitroxyl radicals in the hydrogenated pyrrole series. Tetrahedron, 1965, 21, 491-499.
[20]
(a) Marc, G.; Pecar, S. A short way to esters of 1-oxyl-2,2,5,5-tetramethylpyrrolidine-3-carboxylic acid by Favorskii rearrangement. Synth. Commun., 1995, 25, 1015-1021.
(b) Sosnovsky, G.; Cai, Z. A study of the favorskii rearrangement with 3-Bromo-4-oxo-2,2,6,6-tetramethylpiperidine-1-oxyl. J. Org. Chem., 1995, 60, 3414-3418.
(c)Chudinov, A.V.; Rozantsev, E.G. Halogen containing nitroxyl radicals 3. The synthesis of 3-bromo-4-carboxy-2,2,5,5-tetramethyl-delta 3-pyrrolin-1-oxyl nitroxide radicals; Izv. Akad. Nauk. SSSR Ser. Chim, 1983, pp. 394-397.
[21]
Sholle, V.D.; Krinitskaya, L.A.; Rozantsev, E.G. Unusual oxidation products of certain tertiary amines. Izv. Akad. Nauk SSSR Ser [Khim], 1969, 149-151.
[22]
Sholle, V.D.; Golubev, V.A.; Rozantsev, E.G. Reduction products of nitroxyl radicals of isoindoline series. Izv. Akad. Nauk SSSR Ser [Khim], 1972, 1204-1206.
[23]
Giroud, A.M.; Rassat, A.; Sieveking, H.U.; Nitroxides, L.X.V. Mono et biradicaux derves de l’isondoline. Tetrahedron Lett., 1974, 15, 635-638.
[24]
Kosman, D.J. Spin density distribution in 7-azabicycloheptyl-N-oxyl derivatives. Tetrahedron Lett., 1972, 13, 3317-3320.
[25]
Griffiths, P.G.; Rizzardo, E.; Solomon, D.H. Quantitative studies on free radical reactions with the scavenger 1,1,3,3-tetramethylisoindolinyl-2-oxy. Tetrahedron Lett., 1982, 23, 1309-1312.
[26]
(a) Reid, D.A.; Bottle, S.E.; Micallef, A. The synthesis of water soluble isoindoline nitroxides and a pronitroxide hydroxylamine hydrochloride UV-VIS probe for free radicals. Chem. Commun., 1998, 1907-1908.
(b) Bottle, S.E.; Gillies, D.G.; Hughes, D.L.; Micallef, A.S.; Smirnov, A.I.; Sutcliffe, L.H. Synthesis, single crystal X-ray structure and W-band (95 GHz) EPR spectroscopy of new anionic isoindoline aminoxyl: Synthesis and characterization of some dervatives. J. Chem. Soc., Perkin Trans. 2, 2000, 1285-1291.
[27]
Kálai, T.; Balog, M.; Jekő, J.; Hideg, K. Synthesis and reactions of a symmetric paramagnetic pyrrolidine diene. Synthesis, 1999, 973-980.
[28]
(a) Berti, C.; Greci, L. Nucleophilic substitutions on 1,2-dihydro-2,2-disubstituted-3-oxo-3H-indole-l-oxyl Radicals. Direct acyloxylation and methoxylation. J. Org. Chem., 1981, 46, 3060-3063.
(b) Colonna, M.; Greci, L.; Poloni, M. Stable nitroxide radicals. reaction between 2-cyano-and 4-cyanobenzoquinoline N-Oxides and the Grignard Reagent. J. Heterocycl. Chem., 1980, 17, 1473-1477.
[29]
(a) Venditti, E.; Sciré, A.; Tanfani, F.; Greci, L.; Damiani, A. Nitroxides are more efficient inhibitors of oxidative damage to calf skin collagen than antioxidant vitamins. BBA, 2008, 1780, 58-68.
(b) Carloni, P.; Damiani, E.; Scattolini, M.; Stipa, P.; Greci, L. Reactivity of 2,2-diphenyl-1,2-dihydro-4-ethoxyquinilin-1-yloxyl towards oxygen and carbon–centerd radicals. J. Chem. Soc., Perkin Trans. 2, 2000, 447-451.
(c)Greci, L.; Damiani, E.; Carloni, P.; Stipa, P. Indolinic and quinolinic aminoxyls biological antioxidants.in Free Radicals in Biology and Environment; Minisci, F., Ed.; Kluwer Academic Press: New York, 1997, pp. 223-232.
[30]
Rassat, A.; Sieveking, H.U. A stable aromatic diradicals with strong dipolar electronic interaction. Angew. Chem. Int. Ed., 1972, 11, 303-304.
[31]
Kulcsár, G.; Kálai, T.; Jekő, J.; Hideg, K. Synthesis of paramagnetic carbo-and heterocycles. Synthesis, 2003, 1361-1366.
[32]
Hideg, K.; Hankovszky, H.O.; Lex, L.; Kulcsár, Gy. Nitroxyls; VI. Synthesis and reactions of 3-hydroxymethyl-2,2,5,5-tetramethyl-2,5-dihydro-pyrrole-1-oxyl and 3-formyl derivatives. Synthesis, 1980, 911-914.
[33]
Kálai, T.; Sár, P.C.; Jekő, J.; Hideg, K. Synthesis of new pyrrolidine nitroxide epoxides as versatile paramagnetic building blocks. Tetrahedron Lett., 2002, 43, 8125-8127.
[34]
Rozantsev, E.G. Shapiro, A.B.; Komzolova, N.N. Paramagnetic derivatives in 1,2,3,4-tetrahydro-γ-carboline series. Izv. Akad. Nauk SSSR [Khim], 1965, 1100-1102.
[35]
Shapiro, A.B.; Rozantsev, E.G.; Povarov, L.S.; Grigos, V.I. Paramagnetic derivatives in the series of hydrogenated quinolones. Izv. Akad Nauk. Ser. Khim, 1965, 1102-1104.
[36]
Rosnati, V.; Palazzo, G. The synthesis of some 5-carbolines by the Fischer reaction. Gaz. Chim. Ital, 1954, 644-648.
[37]
Mikhailov, B.M.; Povarov, L.S.; Grigos, V.I.; Karakhanov, R.A. Reactions of dihydrosylvan with Schiff bases. Izv. Akad Nauk. Ser. Khim, 1964, 1693- 1695.
[38]
Keana, J.F.W.; Hideg, K.; Birrell, G.B.; Hankovszky, H.O.; Ferguson, G.; Parvez, M. New mono- and difunctionalized 2,2,5,5-tetramethylpyrrolidine- and Δ3-pyrroline-1-oxyl nitroxide spin labels. Can. J. Chem., 1982, 60, 1439-1447.
[39]
Kálai, T.; Balog, M.; Jekő, J.; Hideg, K. 3-Substituted-2,2,5,5-tetramethyl 2,5-dihydro-1H-pyrrol-1-yloxyl radicals as versatile synthons for synthesis of new paramagnetic heterocycles. Synthesis, 1998, 30, 1476-1482.
[40]
Tan, N.P.H.; Taylor, M.K. Bottle, S.E.; Wright, C.E.; Zioga, J.; White, J.M.; Schiesser, C.H.; Jani, N.V. Novel paramagnetic AT1 receptor antagonists. Chem. Commun., 2011, 47, 12083-12085.
[41]
Hideg, K.; Kálai, T.; Sár, P.C. Recent results in chemistry and biology of nitroxides. J. Heterocycl. Chem., 2005, 42, 437-450.
[42]
Bognár, B.; Sár, P.C.; Hankovszky, H.O.; Kálai, T.; Hideg, K. Synthesis and application of stable nitroxide free radicals (in Hungarian). Magy. Kem. Foly., 2013, 119, 80-87.
[43]
Volodarskii, L.B.; Grigor’eva, L.N.; Dulepova, N.V.; Tikhonov, A.Ya. Preparation of α-hydroxylaminooximes of triacetonamine derivative and their reactions with carbonyl compounds. Izv. Akad. Nauk SSSR Ser [Khim], 1988, 409-412.
[44]
Kálai, T.; Jekő, J.; Hideg, K. Synthesis of pyrroline nitroxide annulated carbocycles and heterocycles. Synthesis, 2000, 831-837.
[45]
Babic, A.; Pecar, S. Synthesis of novel bicyclic nitroxides using partial Favorskii rearrangement. Synlett, 2008, 1155-1158.
[46]
Zubenko, D.; Tsentalovich, Y.; Lebedeva, N.; Kirilyuk, I.; Roschupkina, G.; Zhurko, I.; Reznikov, V.; Marque, S.R.A.; Bagryankaya, E. Laser flash photolysis and CIDNP studies of steric effects on coupling rate constants of imidazolidine nitroxide with carbon-centered radicals, methyl isobutyrate-2-yl and tert-butyl propionate-2-yl. J. Org. Chem., 2006, 71, 6044-6052.
[47]
Micallef, A.S.; Blinco, J.P.; George, J.A.; Reid, D.A.; Rizzardo, E.; Thang, S.H.; Bottle, S.E. The application of a novel profluorescent nitroxide to monitor thermo-oxidative degradation of polypropylene. Polym. Degrad. Stabil., 2005, 89, 427-435.
[48]
Kálai, T.; Jekő, J.; Berente, Z.; Hideg, K. Palladium-catalyzed cross-coupling reactions of paramagnetic vinyl bromides and paramagnetic boronic acids. Synthesis, 2006, 439-446.
[49]
Blinco, J.P.; McMurtie, J.C.; Bottle, S.E. The first example of an azaphenalene profluorescent nitroxide. Eur. J. Org. Chem., 2007, 4638-4641.
[50]
Bottle, S.E.; Clement, J.L.; Fleige, M.; Simpson, E.M.; Guillaneuf, Y.; Fairfull-Smith, K.E.; Gigmes, D.; Blinco, J.P. Light-active azaphenalene alkoxyamines: fast and efficient mediators of a photo-induced persistent radical effect. RSC Adv., 2016, 6, 80328-80333.
[51]
Kálai, T.; Jekő, J.; Hideg, K. Synthesis of isoindoline nitroxides by electrocyclic reactions. Synthesis, 2009, 41, 2591-2595.
[52]
Kálai, T.; Bognár, B.; Zsolnai, D.; Berente, Z.; Hideg, K. Synthesis of nitroxide annulated carbocycles and heterocycles. Synthesis, 2012, 3655-3660.
[53]
Fairfull-Smith, K.E.; Brackmann, F.; Bottle, S.E. The synthesis of novel isoindoline nitroxides bearing water-solubiliznig functionality. Eur. J. Org. Chem., 2009, 1902-1915.
[54]
(a) Blinco, J.P.; Hodgson, J.L.; Morrow, J.B.; Walker, J.R.; Will, D.F.; Coote, M.L.; Bottle, S.E. Experimental and theoretical studies of the redox potentials of cyclic nitroxides. J. Org. Chem., 2008, 73, 6763-6771.
(b) Gry’nova, G.; Barakt, J.M.; Blinco, J.P.; Bottle, S.E.; Coote, M.L. Computational design of cyclic nitroxides as efficient redox mediators for dye-sensitized solar cells. Chem. Eur. J., 2012, 18, 7582-7593.
[55]
Khan, N.; Blinco, J.P.; Bottle, S.E.; Swartz, H.M.; Micallef, A.S. The evaluation of new and isotopically labaled isondoline nitroxides and azaphenalene nitroxide for EPR oximetry. J. Magn. Reson., 2011, 211, 170-177.
[56]
Fairfull-Smith, K.E.; Debele, A.E.; Allen, J.P.; Pfunder, M.C.; McMurtie, J.C. Direct iodination of isoindolines and isoindoline nitroxides as precursors to functionalized nitroxides. Eur. J. Org. Chem., 2013, 4829-4835.
[57]
Rayner, C.L.; Bottle, S.E.; Gole, G.A.; Ward, S.M.; Barnett, N.L. Real-time quantification of oxidative stress and the protective effect of nitroxide antioxidants. Neurochem. Int., 2016, 92, 1-12.
[58]
Verderosa, D.A. Fuente-Nunez de la C.; Mansour, S.C.; Cao, J.; Lu, K.T.; Hankock, R.E.W.; Fairful-Smith K.E. Ciprofloxacin-nitroxide hybrids with potential biofilm control. Eur. J. Med. Chem., 2017, 138, 590-601.
[59]
Thomas, K.; Mody, T.W.; Jensen, R.T.; Tong, J.; Rayner, C.L.; Barnett, N.L.; Fairfull-Smith, K.E.; Ridnour, L.A.; Wink, D.A.; Bottle, S.E. Design, synthesis and biological evaluation of hybrid nitroxide-based non-steroidal anti-inflammatory drugs. Eur. J. Med. Chem., 2018, 147, 34-47.
[60]
Kálai, T.; Borza, E.; Antus, C.S.; Radnai, B.; Gulyás-Fekete, G.; Fehér, A.; Sümgi, B.; Hideg, K. Synthesis and study of new paramagnertic resveratrol analogues. Bioorg. Med. Chem., 2011, 19, 7311-7317.
[61]
Kálai, T.; Balog, M.; Szabó, A.; Gulyás, G.; Jekő, J.; Sümegi, B.; Hideg, K. New poly(ADP-ribose) polymerase-1 inhibitors with antioxidant activity based on 4-carboxamidobenzimidazole-2-ylpyrroline and tetrahydropyridine nitroxides and their precursors. J. Med. Chem., 2009, 52, 1619-1629.
[62]
Thorsell, A-G.; Ekblad, T.; Karberg, T.; Löw, M.; Pinto, A.F.; Trésaugues, L.; Moche, M.; Cohen, M.S.; Schüler, H. Structural basis for potency and promiscuity in poly(ADP-ribose) polymerase (PARP) and tankyrase inhibitors. J. Med. Chem., 2017, 60, 1262-1271.
[63]
Keddie, J.D.; Fairfull-Smith, K.E.; Bottle, S.E. The palladium-catalysed copper-free Sonogashira coupling of isoindoline nitroxides: A convenient route to robust profluorescent carbon-carbon frameworks. Org. Biomol. Chem., 2008, 6, 3135-3143.
[64]
Lussini, C.V.; Blinco, J.P.; Fairfull-Smith, K.E.; Bottle, S.E. Polyaromatic profluorescent nitroxide probes with enhanced photostability. Chem. Eur. J., 2015, 21, 18258-18268.
[65]
Morris, J.C.; McMurtrie, J.C.; Bottle, S.E.; Fairfull-Smith, K.E. Generation of profluorescent isoindoline nitroxides using click chemistry. J. Org. Chem., 2011, 76, 4964-4972.
[66]
Allen, J.P.; Pfrunder, C.M.; McMurtrie, J.C.; Bottle, S.E.; Blinco, J.P.; Fairfull-smith, K.E. BODIPY-Based profluorescent probes containing meso and β-Substituted Isoindoline Nitroxides. Eur. J. Org. Chem., 2017, 476-483.
[67]
Yan, G.P.; Fairfull-Smith, K.E.; Smith, C.D.; Hanson, G.R.; Bottle, S.E. Porphyrin containing isoindolone nitroxides as potential fluorescence sensors for free radicals. J. Porphyr., 2011, 15, 230-239.
[68]
Liu, F.; Shen, Y-C.; Ouyang, Y-H.; Yan, P.G.; Chen, S.; Liu, H.; Wu, Y-G.; Wu, J-Y. Synthesis and properties of isoindoline nitroxide‐containing porphyrins. J. Heterocycl. Chem., 2017, 54, 3143-3151.
[69]
Saha, S.; Jagtap, A.P.; Sigurdsson, S.Th. Site directed spin labeling of 2′-amino groups in RNA with isoindoline nitroxides that are resistant to reduction. Chem. Commun., 2015, 51, 13142-13145.
[70]
Jagtap, A.P.; Krstic, I.; Kunjir, N.C.; Hansel, R.; Prisner, T.F.; Sigurdsson, T.S. Sterically shielded spin labels for in-cell EPR spectroscopy: Analysis of stability in reducing environment. Free Radic. Res., 2015, 49, 78-85.
[71]
Jacobsen, U.; Shelke, S.A.; Vogel, S.; Sigurdsson, S.T. Site-directed spin-labeling of nucleic acids by click chemistry: Detection of sites in duplex DNA by EPR spectroscopy. J. Am. Chem. Soc., 2010, 132, 10424-10428.
[72]
Haugland, M.M.; ElSagheer, A.H.; Porter, J.P.; Pena, J.; Brown, T.; Anderson, E.A.; Lovett, J.E. 2′-Alkynylnucleosides: A sequence-and spin label-flexible strategy for EPR spectroscopy in DNA. J. Am. Chem. Soc., 2016, 138, 9069-9072.
[73]
Bathae, C.; Cekan, P. Massey, A.P.; Sigurdsson, S.T. A nucleoside that contains a rigid nitroxide spin label: A fluorophore in disguise. Angew. Chem. Int. Ed., 2007, 46, 2655-2658.
[74]
(a) Cekan, P.; Sigurdsson, S.T. Single base interrogation by a flurescent nucleotide: Each of the four DNA bases identified by fluorescence spectroscopy. Chem. Commun., 2008, 3393-3395.
(b) Shelke, S.A.; Sigurdsson, S.T. Noncovalent and site-directed spin labeling of nucleic acids. Angew. Chem. Int. Ed., 2010, 49, 7984-7986.
[75]
Chalmers, B.A.; Saha, S.; Nguyen, S.; McMurtrie, J.; Sigurdsson, T.S.; Bottle, S.E.; Masters, K-S. TMIO-PyrImid hybrids are profluorescent, site–directed spin labels for nucleic acids. Org. Lett., 2014, 16, 5528-5531.
[76]
Kamble, N.R.; Sigurdsson, S.T. Purine-derived nitroxides for noncovalent spin-labeling of abasatic sites in dublex nucleic acids. Chem. Eur. J., 2018, 24, 4157-4164.
[77]
Kálai, T.; Schindler, J.; Balog, M.; Fogassy, E.; Hideg, K. Synthesis and resolution of new paramagnetic α-amino acids. Tetrahedron, 2008, 64, 1094-1100.
[78]
Summerer, D.; Schmidt, M.; Drescher, M. Lysine and tyrosine aminoxyl radical derivatives, a modified pyrrolysyl-t-RNA-synthase, and their use in generating proteins having genetically encoded spin. labels. Patent WO2015107071. July 23. 2015.
[79]
Hansen, K-A.; Nerkar, J.; Thomas, K.; Bottle, S.E.; O’Mullane, A.P.; Talbot, P.C.; Blinco, J.P. New spin on organic radical batteries-An isoindoline nitroxide based high voltage cathode marerial. ACS Appl. Mater. Interfaces, 2018, 10, 7982-7988.
[80]
Li, L.; Matsuda, R.; Tanaka, I.; Sato, H.; Prakash, K.; Jeon, J.H.; Foo, L.M.; Wakamiya, A.; Murata, Y.; Kitagawa, S. A crystalline porous coordination polymer decorated with nitroxyl radicals catalyzes aerobic oxidation of alcohols. J. Am. Chem. Soc., 2014, 136, 7543-7546.
[81]
Schiemann, O.; Cekan, P.; Margaf, D.; Prisner, T.; Sigurdsson, S.T. Angew. Chem. Int. Ed., 2009, 48, 3292-3295.
[82]
Gophane, D.B.; Endeward, B.; Prisner, T.F.; Sigurdsson, S.T. A semi-rigid isoindoline-derived nitroxide spin label for RNA. Org. Biomol. Chem., 2018, 16, 816-824.
[83]
Kálai, T.; Bagi, N.; Jekő, J.; Berente, Z.; Hideg, K. Synthesis of new paramagnetic selenophenes. Synthesis, 2010, 42, 1702-1706.
[84]
Bognár, B.; Kálai, T.; Gulyás-Fekete, G.; Lazsányi, N.; Hideg, K. Synthesis of azoles condensed with, or linked to, nitroxides. Synthesis, 2015, 47, 985-991.
[85]
Bothe, S.; Nowag, J.; Klimavicius, V.; Hoffmann, M.; Troitskaya, T.L.; Amosov, E.V.; Tormyshev, V.M.; Kirilyuk, I.; Taratayko, A.; Kuzhelev, A.; Parkhomenko, D.; Bagryanskaya, E.; Gutmann, T.; Buntkowsky, G. Novel biradical for direct excitation highfield nuclear polarization. J. Phys. Chem. C, 2018, 122, 11422-11432.
[86]
Bognár, B.; Kálai, T.; Hideg, K. Synthesis of benzimidazoles condensed with, or linked to nitroxides or heterocyclic N-oxides. Synthesis, 2008, 40, 2439-2445.
[87]
Balkrishna, S.H.; Bhakuni, S.B.; Chopra, D.; Kumar, S. Cu-catalyzed efficient synthetic methodology for ebselen and related Se−N heterocycles. Org. Lett., 2010, 12, 5394-5397.
[88]
Úr, Gy.; Gulyás-Fekete, G.; Jekő, J.; Hideg, K.; Kálai, T. Palladium-and/or copper–catalyzed cross-coupling reactions of paramagnetic vinyl bromides and iodides. Synthesis, 2017, 49, 3740-3748.
[89]
Úr, Gy.; Kálai, T.; Balog, M.; Bognár, B.; Gulyás-Fekete, G.; Hideg, K. Synthesis of new pyrroline nitroxides with ethynyl functional group. Synth. Commun., 2015, 45, 2122-2129.
[90]
Bognár, B.; Varga, B.; Kálai, T.; Csokona, V.; Gulyás Fekete, G.; Sár, C.; Hideg, K. Reaction of β-bromo-β,γ-unsaturated pyrroline nitroxide aldehydes and nitriles with aromatic S, N-binucleophiles. J. Heterocycl. Chem., 2017, 54, 2556-2562.
[91]
Kálai, T.; Altman, R.; Maezawa, I.; Blog, M.; Morisseau, C.; Petrlova, J.; Hammock, B.D.; Jin, L.W.; Trudell, J.R.; Voss, C.J.; Hideg, K. Synthesis and functional survey of new Tacrine analogs modified with nitroxides or precursors. Eur. J. Med. Chem., 2014, 77, 343-350.
[92]
Úr, Gy.; Gulyás Fekete, G.; Hideg, K.; Kálai, T. N-vinylation of imidazole and benzimidazole with paramagnetic vinyl bromide. Molbank, 2018, 2018, M980.
[93]
Úr, Gy.; Kálai, T.; Hideg, K. Facile syntheses of 3,4-disubstituted pyrroline nitroxides and their further synthetic applications. Tetrahedron Lett., 2018, 57, 778-780.
[94]
Paletta, J.T.; Pink, M.; Foley, B.; Rajca, S.; Rajca, A. synthesis and reduction kinetics of sterically shielded pyrrolidine nitroxides. Org. Lett., 2012, 14, 5322-5325.
[95]
Dobrynin, S.A.; Galazachev, Y.I.; Gatilov, Y.V.; Chernyak, E.I.; Salnikov, G.E.; Kirilyuk, I.A. Synthesis of 3,4-bis(hydroxymethyl)2,2,5,5-tetraethyl-pyrrolidin-1-oxyl via1,3-dipolar cycloaddition of azomethine ylide to activated alkene. J. Org. Chem., 2018, 83, 5392-5397.
[96]
Chong, K.L.; Chalmers, B.A.; Cullen, J.K.; Kaur, A.; Kolanowski, J.L.; Morrow, B.J.; Fairfull-Smith, K.E.; Lavin, J.M.; Barnett, N.L.; New, J.E.; Murphy, M.P.; Bottle, S.E. Pro-fluorescent mitochondria-targeted real time responsive redox probes synthesized from carboxy isoindoline nitroxides: Sensitive probes of mitochondrial redox status in the cells. Free Radic. Biol. Med., 2018, 128, 97-110.
[97]
Bagryanskaya, E.G.; Krumkacheva, O.A.; Fedin, M.V.; Marque, S.R.A. Development and application of spin traps, spin probes, and spin labels. Methods Enzymol., 2015, 563, 365-396.
[98]
Shundrin, L.A.; Kirilyuk, I.A.; Grigor’ev, I.A. 3-Carboxy-2,2,5,5-tetra(H-2(3))methyl-[4-H-2 (H-1)]-3-pyrroline-(1-N-15)-1-oxyl as a spin probe for in vivo L-band electron paramagnetic resonance imaging. Mendeleev Commun., 2014, 24, 298-300.
[99]
Takahashi, Y.; Mutsuhashi, R.; Miura, Y.; Yoshioka, N. Magnetic interactions through a nonconjugated framework observed in back-to-back connected triazinyl-nitroxyl biradical derivatives. Chem. Eur. J, 2018, 24, 7939-7948.
[100]
Saha, S.; Hetzke, T.; Prisner, F.T.; Sigurdsson, S.T. Noncovalent spin-labeling of RNA: the aptamer approach. Chem. Commun., 2018, 54, 11749-11752.

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