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Amram Samuni - One of the best experts on this subject based on the ideXlab platform.
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Nitroxides catalytically inhibit nitrite oxidation and heme inactivation induced by h2o2 nitrite and metmyoglobin or methemoglobin
Free Radical Biology and Medicine, 2016Co-Authors: Amram Samuni, Eric Maimon, Sara GoldsteinAbstract:Abstract Stable Nitroxide radicals have multiple biological effects, although the mechanisms underlying them are not fully understood. Their protective effect against oxidative damage has been mainly attributed to scavenging deleterious radicals, oxidizing reduced metal ions and reducing oxyferryl centers of heme proteins. Yet, the potential of Nitroxides to protect heme proteins against inactivation while suppressing or enhancing their catalytic activities has been largely overlooked. We have studied the effect of Nitroxides, including TPO (2,2,6,6-tetramethylpiperidin-N-oxyl), 4-OH-TPO, 4-oxo-TPO and 3-carbamoyl proxyl, on the peroxidase-like activity of metmyoglobin (MbFeIII) and methemoglobin (HbFeIII) using nitrite as an electron donor by following heme absorption, H2O2 consumption, O2 evolution and nitrite oxidation. The results demonstrate that the peroxidase-like activity is accompanied by a progressive heme inactivation where MbFeIII is far more resistant than HbFeIII. Nitroxides convert the peroxidase-like activity into catalase-like activity while inhibiting heme inactivation and nitrite oxidation in a dose-dependent manner. The Nitroxide facilitates H2O2 dismutation, yet none of its reactions with any of the intermediates formed in these systems is rate-determining, and therefore its effect on the rate of the catalysis is hardly dependent on the kind of the Nitroxide derivative and its concentration. The Nitroxide at µM concentrations range catalytically inhibits nitrite oxidation, and consequently prevents tyrosine nitration induced by heme protein/H2O2/nitrite due to its fast oxidation by •NO2 forming the respective oxoammonium cation, which is reduced back to the Nitroxide by H2O2 and by superoxide radical. The Nitroxides are superior over common antioxidants, which their reaction with •NO2 always yields secondary radicals leading eventually to consumption of the antioxidant. A mechanism is proposed, and the kinetic simulations fit very well the experimental data in the case of MbFeIII where most of the rate constants of the reactions involved are independently known.
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Kinetics of the reaction between Nitroxide and thiyl radicals: Nitroxides as antioxidants in the presence of thiols.
The journal of physical chemistry. A, 2008Co-Authors: Sara Goldstein, Amram Samuni, Gabor MerenyiAbstract:Cyclic Nitroxides effectively protect cells, tissues, isolated organs, and laboratory animals from radical-induced damage. The present study focuses on the kinetics and mechanisms of the reactions of piperidine and pyrrolidine Nitroxides with thiyl radicals, which are involved in free radical "repair" equilibria, but being strong oxidants can also produce cell damage. Thiyl radicals derived from glutathione, cysteine, and penicillamine were generated in water by pulse radiolysis, and the rate constants of their reactions with 2,2,6,6-tetramethylpiperidine-1-oxyl (TPO), 4-OH-TPO, and 3-carbamoyl-proxyl were determined to be (5-7) x 10 (8) M (-1) s (-1) at pH 5-7, independent of the structure of the Nitroxide and the thiyl radical. It is suggested that the reaction of Nitroxide (>NO (*)) with thiyl radical (RS (*)) yields an unstable adduct (>NOSR). The deprotonated form of this adduct decomposes via heterolysis of the N-O bond, yielding the respective amine (>NH) and sulfinic acid (RS(O)OH). The protonated form of the adduct decomposes via homolysis of the N-O bond, forming the aminium radical (>NH (*+)) and sulfinyl radical (RSO (*)), which by subsequent reactions involving thiol and Nitroxide produce the respective amine and sulfonic acid (RS(O) 2OH). Nitroxides that are oxidized to the respective oxoammonium cations (>N (+)O) are recovered in the presence of NADH but not in the presence of thiols. This suggests that the reaction of >N (+)O with thiols yields the respective amine. Two alternative mechanisms are suggested, where >N (+)O reacts with thiolate (RS (-)) directly generating the adduct >NOSR or indirectly forming >NO (*) and RS (*), which subsequently together yield the adduct >NOSR. Under physiological conditions the adduct is mainly deprotonated, and therefore Nitroxides can detoxify thiyl radicals. The proposed mechanism can account for the protective effect of Nitroxides against reactive oxygen- and nitrogen-derived species in the presence of thiols.
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kinetics and mechanism of hydroxyl radical and oh adduct radical reactions with Nitroxides and with their hydroxylamines
Journal of the American Chemical Society, 2002Co-Authors: Amram Samuni, Murali C. Krishna, James B. Mitchell, Sara Goldstein, Angelo Russo, P NetaAbstract:Stable Nitroxide radicals are potent antioxidants and are among the most effective non-thiol radioprotectants, although they react with hydroxyl radicals more slowly than typical phenolic antioxidants or thiols. Surprisingly, the reduced forms of cyclic Nitroxides, cyclic hydroxylamines, are better reductants yet have no radioprotective activity. To clarify the reason for this difference, we studied the kinetics and mechanisms of the reactions of Nitroxides and their hydroxylamines with •OH radicals and with OH-adducts by using pulse radiolysis, fluorimetric determination of phenolic radiation products, and electron paramagnetic resonance spectrometric determination of Nitroxide concentrations following radiolysis. Competition kinetics with phenylalanine as a reference compound in pulse radiolysis experiments yielded rate constants of (4.5 ± 0.4) × 109 M-1 s-1 for the reaction of •OH radical with 2,2,6,6-tetramethylpiperidine-N-oxyl (TPO), 4-hydroxy-TPO (4-OH-TPO), and 4-oxo-TPO (4-O-TPO), (3.0 ± 0.3) × 1...
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Kinetics of Nitroxide Reaction with Iron(II)
Journal of the American Chemical Society, 1999Co-Authors: Pazit Bar-on, Mohammad Mohsen, Renliang Zhang, Elad Feigin, Mordechai Chevion, Amram SamuniAbstract:Like superoxide dismutase (SOD), Nitroxide stable radicals can catalyze the dismutation of superoxide radicals and provide protection against oxidative stress. The SOD-mimic activity of Nitroxides ...
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do Nitroxide antioxidants act as scavengers of o2 or as sod mimics
Journal of Biological Chemistry, 1996Co-Authors: Murali C. Krishna, James B. Mitchell, Sara Goldstein, Angelo Russo, Hagit Dafni, Amram SamuniAbstract:Stable Nitroxide radicals were reported to act as SOD mimics and catalyze the dismutation of O2-. through two different catalytic pathways including reductive and oxidative reaction mechanisms (Samuni, A., Krishna, C. M., Riesz, P., Finkelstein, E. & Russo, A. (1988) J. Biol Chem. 263, 17921-17924). Recent studies directly monitoring O2-. and employing kinetics analysis did not reveal SOD activity of Nitroxides (Weiss, R. H., Flickinger, A. G., Rivers, W. J., Hardy, M. M., Aston, K. W., Ryan, U. S. & Riley, D. P. (1993) J. Biol. Chem. 268, 23049-23054). Such discrepancy may result in cases where distinction of stoichiometric scavengers from catalytic detoxifiers of O2-. is not readily feasible. Nitroxides are effective antioxidants that protect against oxidative injury in various pathological processes. The distinction of their SOD mimic activity from O2-. scavenging was established by examining the validity of direct and indirect methods employed to assay SOD-like catalytic activity. Kinetics analysis along with direct EPR monitoring were used to study the mechanism underlying Nitroxide reactions with O2-.. The Nitroxide EPR signal decayed in the presence of NADH but otherwise did not decrease with time, thus substantiating its catalytic role in O2-. dismutation. The catalytic rate constants for O2-., dismutation, determined for the Nitroxides tested, were found to increase with [H+], indicating that .OOH rather than O2-. is oxidizing the Nitroxide. The results demonstrate the limitations associated with direct kinetics analysis in evaluating SOD mimic activity, underscoring the need for independent assays for valid discrimination of SOD mimics from stoichiometric scavengers of O2-..
Murali C. Krishna - One of the best experts on this subject based on the ideXlab platform.
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An efficient synthesis of 3-(N-piperidinemethyl)-2, 2, 5, 5-tetramethyl-1-oxy-3-pyrroline, a promising radioprotector for cancer radiotherapy
Tetrahedron Letters, 2014Co-Authors: Vincent Coble, Murali C. Krishna, Olga Vasalatiy, Rolf E. Swenson, James B. MitchellAbstract:Nitroxides can ameliorate the toxic effects of radiation during cancer therapy. Nitroxides are paramagnetic and can be used in magnetic resonance imaging (MRI) and electron paramagnetic resonance imaging (EPRI) to monitor in vivo oxidative stress status. Compound 5 (3-(N-piperidinemethyl)-2,2,5,5-tetramethyl-1-oxy-3-pyrroline) was found to be the most effective Nitroxide radioprotector. An efficient synthesis for this promising radioprotector was developed.
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Nitroxides as cancer imaging agents.
Anti-cancer agents in medicinal chemistry, 2011Co-Authors: Ryan M. Davis, James B. Mitchell, Murali C. KrishnaAbstract:Nitroxides are low molecular weight (150-400 Da) superoxide dismutase mimics that exhibit antioxidant, radical scavenging, and radioprotective activity. Additionally, the paramagnetic nature of Nitroxides makes them viable as both spin probes for electron paramagnetic resonance imaging as well as contrast agents for magnetic resonance imaging. These imaging techniques enable in vivo monitoring of Nitroxide metabolism. In biological systems, Nitroxide metabolism occurs predominantly via reduction of the Nitroxide to a hydroxylamine. The rate of Nitroxide reduction can increase or decrease due to either oxidative stress, suggesting that Nitroxides can provide an imaging-based assay of tissue redox status. The current review briefly summarizes the potential clinical applications of Nitroxides, and focuses on the biochemical and tumor microenvironmental factors that affect the rate of Nitroxide reduction. The potential therapeutic applications and bio-reduction mechanisms are discussed in the context of their relevance to oncology.
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kinetics and mechanism of hydroxyl radical and oh adduct radical reactions with Nitroxides and with their hydroxylamines
Journal of the American Chemical Society, 2002Co-Authors: Amram Samuni, Murali C. Krishna, James B. Mitchell, Sara Goldstein, Angelo Russo, P NetaAbstract:Stable Nitroxide radicals are potent antioxidants and are among the most effective non-thiol radioprotectants, although they react with hydroxyl radicals more slowly than typical phenolic antioxidants or thiols. Surprisingly, the reduced forms of cyclic Nitroxides, cyclic hydroxylamines, are better reductants yet have no radioprotective activity. To clarify the reason for this difference, we studied the kinetics and mechanisms of the reactions of Nitroxides and their hydroxylamines with •OH radicals and with OH-adducts by using pulse radiolysis, fluorimetric determination of phenolic radiation products, and electron paramagnetic resonance spectrometric determination of Nitroxide concentrations following radiolysis. Competition kinetics with phenylalanine as a reference compound in pulse radiolysis experiments yielded rate constants of (4.5 ± 0.4) × 109 M-1 s-1 for the reaction of •OH radical with 2,2,6,6-tetramethylpiperidine-N-oxyl (TPO), 4-hydroxy-TPO (4-OH-TPO), and 4-oxo-TPO (4-O-TPO), (3.0 ± 0.3) × 1...
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do Nitroxide antioxidants act as scavengers of o2 or as sod mimics
Journal of Biological Chemistry, 1996Co-Authors: Murali C. Krishna, James B. Mitchell, Sara Goldstein, Angelo Russo, Hagit Dafni, Amram SamuniAbstract:Stable Nitroxide radicals were reported to act as SOD mimics and catalyze the dismutation of O2-. through two different catalytic pathways including reductive and oxidative reaction mechanisms (Samuni, A., Krishna, C. M., Riesz, P., Finkelstein, E. & Russo, A. (1988) J. Biol Chem. 263, 17921-17924). Recent studies directly monitoring O2-. and employing kinetics analysis did not reveal SOD activity of Nitroxides (Weiss, R. H., Flickinger, A. G., Rivers, W. J., Hardy, M. M., Aston, K. W., Ryan, U. S. & Riley, D. P. (1993) J. Biol. Chem. 268, 23049-23054). Such discrepancy may result in cases where distinction of stoichiometric scavengers from catalytic detoxifiers of O2-. is not readily feasible. Nitroxides are effective antioxidants that protect against oxidative injury in various pathological processes. The distinction of their SOD mimic activity from O2-. scavenging was established by examining the validity of direct and indirect methods employed to assay SOD-like catalytic activity. Kinetics analysis along with direct EPR monitoring were used to study the mechanism underlying Nitroxide reactions with O2-.. The Nitroxide EPR signal decayed in the presence of NADH but otherwise did not decrease with time, thus substantiating its catalytic role in O2-. dismutation. The catalytic rate constants for O2-., dismutation, determined for the Nitroxides tested, were found to increase with [H+], indicating that .OOH rather than O2-. is oxidizing the Nitroxide. The results demonstrate the limitations associated with direct kinetics analysis in evaluating SOD mimic activity, underscoring the need for independent assays for valid discrimination of SOD mimics from stoichiometric scavengers of O2-..
Andrzej Rajca - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of unnatural amino acids functionalized with sterically shielded pyrroline Nitroxides
Organic letters, 2014Co-Authors: Ying Wang, Joseph T Paletta, Suchada Rajca, Kathleen E. Berg, Erin F. Reinhart, Andrzej RajcaAbstract:A series of unnatural amino acids functionalized with sterically shielded pyrroline Nitroxides were synthesized. Their reduction by ascorbate/glutathione indicates that l-cysteine functionalized with gem-diethylpyrroline Nitroxide is reduced at the slowest rate and is comparable to that measured for the most resistant to reduction pyrroline and pyrrolidine Nitroxides.
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synthesis and reduction kinetics of sterically shielded pyrrolidine Nitroxides
Organic Letters, 2012Co-Authors: Joseph T Paletta, Maren Pink, Bridget Foley, Suchada Rajca, Andrzej RajcaAbstract:A series of sterically shielded pyrrolidine Nitroxides were synthesized, and their reduction by ascorbate (vitamin C) indicate that Nitroxide 3, a tetraethyl derivative of 3-carboxy-PROXYL, is reduced at the slowest rate among known Nitroxides, i.e., at a 60-fold slower rate than that for 3-carboxy-PROXYL.
Sara Goldstein - One of the best experts on this subject based on the ideXlab platform.
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Nitroxides catalytically inhibit nitrite oxidation and heme inactivation induced by h2o2 nitrite and metmyoglobin or methemoglobin
Free Radical Biology and Medicine, 2016Co-Authors: Amram Samuni, Eric Maimon, Sara GoldsteinAbstract:Abstract Stable Nitroxide radicals have multiple biological effects, although the mechanisms underlying them are not fully understood. Their protective effect against oxidative damage has been mainly attributed to scavenging deleterious radicals, oxidizing reduced metal ions and reducing oxyferryl centers of heme proteins. Yet, the potential of Nitroxides to protect heme proteins against inactivation while suppressing or enhancing their catalytic activities has been largely overlooked. We have studied the effect of Nitroxides, including TPO (2,2,6,6-tetramethylpiperidin-N-oxyl), 4-OH-TPO, 4-oxo-TPO and 3-carbamoyl proxyl, on the peroxidase-like activity of metmyoglobin (MbFeIII) and methemoglobin (HbFeIII) using nitrite as an electron donor by following heme absorption, H2O2 consumption, O2 evolution and nitrite oxidation. The results demonstrate that the peroxidase-like activity is accompanied by a progressive heme inactivation where MbFeIII is far more resistant than HbFeIII. Nitroxides convert the peroxidase-like activity into catalase-like activity while inhibiting heme inactivation and nitrite oxidation in a dose-dependent manner. The Nitroxide facilitates H2O2 dismutation, yet none of its reactions with any of the intermediates formed in these systems is rate-determining, and therefore its effect on the rate of the catalysis is hardly dependent on the kind of the Nitroxide derivative and its concentration. The Nitroxide at µM concentrations range catalytically inhibits nitrite oxidation, and consequently prevents tyrosine nitration induced by heme protein/H2O2/nitrite due to its fast oxidation by •NO2 forming the respective oxoammonium cation, which is reduced back to the Nitroxide by H2O2 and by superoxide radical. The Nitroxides are superior over common antioxidants, which their reaction with •NO2 always yields secondary radicals leading eventually to consumption of the antioxidant. A mechanism is proposed, and the kinetic simulations fit very well the experimental data in the case of MbFeIII where most of the rate constants of the reactions involved are independently known.
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Kinetics of the reaction between Nitroxide and thiyl radicals: Nitroxides as antioxidants in the presence of thiols.
The journal of physical chemistry. A, 2008Co-Authors: Sara Goldstein, Amram Samuni, Gabor MerenyiAbstract:Cyclic Nitroxides effectively protect cells, tissues, isolated organs, and laboratory animals from radical-induced damage. The present study focuses on the kinetics and mechanisms of the reactions of piperidine and pyrrolidine Nitroxides with thiyl radicals, which are involved in free radical "repair" equilibria, but being strong oxidants can also produce cell damage. Thiyl radicals derived from glutathione, cysteine, and penicillamine were generated in water by pulse radiolysis, and the rate constants of their reactions with 2,2,6,6-tetramethylpiperidine-1-oxyl (TPO), 4-OH-TPO, and 3-carbamoyl-proxyl were determined to be (5-7) x 10 (8) M (-1) s (-1) at pH 5-7, independent of the structure of the Nitroxide and the thiyl radical. It is suggested that the reaction of Nitroxide (>NO (*)) with thiyl radical (RS (*)) yields an unstable adduct (>NOSR). The deprotonated form of this adduct decomposes via heterolysis of the N-O bond, yielding the respective amine (>NH) and sulfinic acid (RS(O)OH). The protonated form of the adduct decomposes via homolysis of the N-O bond, forming the aminium radical (>NH (*+)) and sulfinyl radical (RSO (*)), which by subsequent reactions involving thiol and Nitroxide produce the respective amine and sulfonic acid (RS(O) 2OH). Nitroxides that are oxidized to the respective oxoammonium cations (>N (+)O) are recovered in the presence of NADH but not in the presence of thiols. This suggests that the reaction of >N (+)O with thiols yields the respective amine. Two alternative mechanisms are suggested, where >N (+)O reacts with thiolate (RS (-)) directly generating the adduct >NOSR or indirectly forming >NO (*) and RS (*), which subsequently together yield the adduct >NOSR. Under physiological conditions the adduct is mainly deprotonated, and therefore Nitroxides can detoxify thiyl radicals. The proposed mechanism can account for the protective effect of Nitroxides against reactive oxygen- and nitrogen-derived species in the presence of thiols.
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kinetics and mechanism of hydroxyl radical and oh adduct radical reactions with Nitroxides and with their hydroxylamines
Journal of the American Chemical Society, 2002Co-Authors: Amram Samuni, Murali C. Krishna, James B. Mitchell, Sara Goldstein, Angelo Russo, P NetaAbstract:Stable Nitroxide radicals are potent antioxidants and are among the most effective non-thiol radioprotectants, although they react with hydroxyl radicals more slowly than typical phenolic antioxidants or thiols. Surprisingly, the reduced forms of cyclic Nitroxides, cyclic hydroxylamines, are better reductants yet have no radioprotective activity. To clarify the reason for this difference, we studied the kinetics and mechanisms of the reactions of Nitroxides and their hydroxylamines with •OH radicals and with OH-adducts by using pulse radiolysis, fluorimetric determination of phenolic radiation products, and electron paramagnetic resonance spectrometric determination of Nitroxide concentrations following radiolysis. Competition kinetics with phenylalanine as a reference compound in pulse radiolysis experiments yielded rate constants of (4.5 ± 0.4) × 109 M-1 s-1 for the reaction of •OH radical with 2,2,6,6-tetramethylpiperidine-N-oxyl (TPO), 4-hydroxy-TPO (4-OH-TPO), and 4-oxo-TPO (4-O-TPO), (3.0 ± 0.3) × 1...
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do Nitroxide antioxidants act as scavengers of o2 or as sod mimics
Journal of Biological Chemistry, 1996Co-Authors: Murali C. Krishna, James B. Mitchell, Sara Goldstein, Angelo Russo, Hagit Dafni, Amram SamuniAbstract:Stable Nitroxide radicals were reported to act as SOD mimics and catalyze the dismutation of O2-. through two different catalytic pathways including reductive and oxidative reaction mechanisms (Samuni, A., Krishna, C. M., Riesz, P., Finkelstein, E. & Russo, A. (1988) J. Biol Chem. 263, 17921-17924). Recent studies directly monitoring O2-. and employing kinetics analysis did not reveal SOD activity of Nitroxides (Weiss, R. H., Flickinger, A. G., Rivers, W. J., Hardy, M. M., Aston, K. W., Ryan, U. S. & Riley, D. P. (1993) J. Biol. Chem. 268, 23049-23054). Such discrepancy may result in cases where distinction of stoichiometric scavengers from catalytic detoxifiers of O2-. is not readily feasible. Nitroxides are effective antioxidants that protect against oxidative injury in various pathological processes. The distinction of their SOD mimic activity from O2-. scavenging was established by examining the validity of direct and indirect methods employed to assay SOD-like catalytic activity. Kinetics analysis along with direct EPR monitoring were used to study the mechanism underlying Nitroxide reactions with O2-.. The Nitroxide EPR signal decayed in the presence of NADH but otherwise did not decrease with time, thus substantiating its catalytic role in O2-. dismutation. The catalytic rate constants for O2-., dismutation, determined for the Nitroxides tested, were found to increase with [H+], indicating that .OOH rather than O2-. is oxidizing the Nitroxide. The results demonstrate the limitations associated with direct kinetics analysis in evaluating SOD mimic activity, underscoring the need for independent assays for valid discrimination of SOD mimics from stoichiometric scavengers of O2-..
Nicholas J Turro - One of the best experts on this subject based on the ideXlab platform.
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Photolysis of endoperoxides in the presence of Nitroxides: a laser flash photolysis study with optical and ESR detection
Photochemical and Photobiological Sciences, 2014Co-Authors: Alberto Moscatelli, Steffen Jockusch, Elena Sartori, Marco Ruzzi, Igor V. Khudyakov, Nicholas J TurroAbstract:Time-resolved electron paramagnetic resonance spectroscopy, transient absorption, and phosphorescence spectroscopy were used to investigate the spin polarization of a Nitroxide free radical induced by interaction with singlet oxygen (1O2). The latter was generated by photolysis of endoperoxides of two anthracene derivatives. Although both anthracene endoperoxides are structurally similar, opposite spin polarization of the Nitroxide was observed. Photolysis of one endoperoxide leads to absorptive Nitroxide spin polarization due to interaction with the generated 1O2. Photolysis of the other endoperoxide generated emissive Nitroxide spin polarization, probably due to interaction of the endoperoxide triplet states with Nitroxides.
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Electron spin polarization transfer from a Nitroxide incarcerated within a nanocapsule to a Nitroxide in the bulk aqueous solution
Journal of Physical Chemistry Letters, 2010Co-Authors: Steffen Jockusch, Olaf Zeika, Nithyanandhan Jayaraj, Vaidhyanathan Ramamurthy, Nicholas J TurroAbstract:A thioxanthone derivative containing a covalently attached (15)N-labeled\nNitroxide. was incarcerated into an octaacid nanocapsule.\nPhotoexcitation of the thioxanthone chromophore generated electron spin\npolarization of the Nitroxide. This spin polarization of the\n(15)N-labeled Nitroxide was transferred through the walls of the\ncarcerand to a (14)N-labeled Nitroxide in external bulk solvent, a\nprocess that was directly observed by time-resolved EPR spectroscopy.\nThe efficiency of the communication between the incarcerated guest and\nmolecules in the bulk solvent was shown to be controlled by\nsupramolecular factors such as Coulombic attraction and repulsion\nbetween the guest@host complex and charged molecules in the bulk solvent\nphase.
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An EPR and NMR Study of Supramolecular Effects on Paramagnetic Interaction between a Nitroxide Incarcerated within a Nanocapsule with a Nitroxide in Bulk Aqueous Media
Journal of the American Chemical Society, 2008Co-Authors: Judy Y.-c. Chen, Nithyanandhan Jayaraj, Vaidhyanathan Ramamurthy, Steffen Jockusch, M. Francesca Ottaviani, Nicholas J TurroAbstract:A 15N-labeled Nitroxide was incarcerated into an octa acid nanocapsule, which was confirmed by 1H NMR and EPR spectroscopy. Electron paramagnetic interaction between the 15N-labeled incarcerated Nitroxide and a 14N-labeled free Nitroxide in the external aqueous solution was observed by EPR spectroscopy. The observation of spin−spin interaction, through the walls of the carcerand is reflected in the simultaneous line-broadening of both the 15N-labeled and 14N-labeled Nitroxides. The computer-assisted analysis of the EPR data further provides direct information on the motion and the polarity of both the incarcerated paramagnetic Nitroxide and the Nitroxides in the external bulk aqueous phase. We also show how communication between an incarcerated guest and molecules in the bulk solvent can be enhanced or inhibited by supramolecular factors such as Coulombic attraction or repulsion between a charged guest@host complex (incarcerated 15N Nitroxide) and charged molecules in the aqueous phase.