Magnetic resonance relaxivity of dendrimer‐linked nitroxides

Winalski, Carl S.; Shortkroff, Sonya; Mulkern, Robert V.; Schneider, Erika; Rosen, Gerald M.

doi:10.1002/mrm.10312

Cited by 71 publications

(71 citation statements)

References 37 publications

(123 reference statements)

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“…Interestingly, in a previous study of dendrimer-linked polynitroxides 12 in aqueous solution, the authors reported constant relaxivity on a per nitroxide basis. The apparent conflict between this result and the results of our study can be explained on the basis of known aggregation effects of nitroxide-labeled dendrimers in aqueous solution.…”

Section: Discussionmentioning

confidence: 96%

“…The dendrimer framework has been shown to be advantageous in decreasing the bioreduction rate of nitroxide in vivo, an extremely rapid process which destroys the relaxation enhancer. 12 The potential of dendritic PREs in targeting specific organs has been investigated. 10,13,15 Our lab has studied stable nitroxide radicals for several years as ESR probes for surfaces and supramolecular assemblies.…”

Section: Introductionmentioning

confidence: 99%

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Relaxivity Studies on Dinitroxide and Polynitroxyl Functionalized Dendrimers: Effect of Electron Exchange and Structure on Paramagnetic Relaxation Enhancement

et al. 2003

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The 1 H NMR relaxivity of o-and p-dinitroxide-substituted phthalate esters and a series of nitroxyl-functionalized poly(propylene imine) dendrimers has been measured in acetonitrile and methanol. Studies of dinitroxide relaxivity indicate that the electron exchange rate has only a small effect on relaxivity. Outer-sphere relaxivity has been measured using benzene as a probe molecule. In studies on dendritic polynitroxides, the per-nitroxidebased outer-sphere relaxivity nearly doubles for the generation 5 nitroxyl-functionalized dendrimer as compared to a mononitroxide model. This relaxivity enhancement may be due to crowding of dendrimer surface groups in higher generation dendrimers. Water relaxivity has been measured for these polynitroxides as well, and a significant inner-sphere contribution to relaxivity is found. Dendritic polynitroxides exhibit higher per-nitroxidebased water relaxivity as compared to a mononitroxide model. This relaxivity enhancement is attributed to an increase in rotational correlation time (τ c ) for the dendritic polynitroxides.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Relaxivity Studies on Dinitroxide and Polynitroxyl Functionalized Dendrimers: Effect of Electron Exchange and Structure on Paramagnetic Relaxation Enhancement

et al. 2003

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“…A number of studies of the reduction of nitroxyl radicals (NR) have been reported (for reviews see [1,2]) because of the importance of this class of the compounds in biology and medicine where they are used as contrast agents for magnetic resonance imaging, MRI [3,4], spin labels [5], superoxide dismutase (SOD)-mimics [6], and antioxidants [7,8]. Chemical reduction of NR to EPR (electron paramagnetic resonance) -silent hydroxylamines (HA) in many cases is an unfavorable factor that significantly limits their applications in biological systems.…”

Section: Introductionmentioning

confidence: 99%

Reversible reduction of nitroxides to hydroxylamines: Roles for ascorbate and glutathione

Bobko

Kirilyuk

Grigor'ev

et al. 2007

Free Radical Biology and Medicine

131

123

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Biological applications of stable nitroxyl radicals, NR, include their use as contrast agents for magnetic resonance imaging, spin labels, superoxide dismutase mimics, and antioxidants. The rapid reduction of NR in biological samples into hydroxylamines, HA, significantly limits their application. In its turn, reoxidation of HA back to the NR has been used for detection of reactive oxygen species, ROS. In this work comparative studies of the reduction of pyrrolidine, imidazoline and imidazolidine NR by ascorbate were performed taking advantage of recently synthesized tetraethyl substituted NR with much higher stability towards reduction both in vitro and in vivo. Surprisingly, these NR kept 10-50% of initial intensity of electron paramagnetic resonance signal for about 1 h in the presence of hundred fold excess of ascorbate. To explain this data, reoxidation of the corresponding HA by ascorbate radical and dehydroascorbic acid back to the NR was proposed. This hypothesis was supported by direct measurement of the NR appearance from the HA upon ascorbate radical generation by ascorbate oxidase, or in the presence of the dehydroascorbic acid. The reversible reaction between NR and ascorbate was observed for the various types of the NR, and the rate constants for direct and reverse reactions were determined. The equilibrium constants for oneelectron reduction of the tetraethyl substituted NR by ascorbate were found to be in the range from 2.65×10 −6 to 10 −5 which is significantly lower than corresponding values for the tetramethyl substituted NR (less or about 10 −4 ). This explains an establishment of EPR-detectable quasiequilibrium level of tetraethyl substituted NR in the presence of excess of ascorbate. The redox reactions of the NR-HA couple in ascorbate containing medium was found to be significantly affected by glutathione, GSH. This effect was attributed to the reduction of ascorbate radical by GSH, and the rate constant of this reaction was found to be equal to 10 M −1 s −1 . In summary, the data provide new insight into the redox chemistry of NR and HA, and significantly affect interpretation and strategy of their use as redox-and ROS-sensitive probes, or as antioxidants.

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“…Recently, the 1,3-alternate calix [4]arene nitroxide tetraradical and diradical were employed as model systems for the study of electron spin relaxation, [25] aimed at the development of functional paramagnetic contrast agents for electron paramagnetic resonance imaging (EPRI) and magnetic resonance imaging (MRI). [26], [27], [28], [29], & [30] These nitroxide polyradicals provide the probes for well-defi ned and moderately strong radical-radical interactions.…”

Section: Introductionmentioning

confidence: 99%

1,3‐Alternate Calix[4]arene Nitronyl Nitroxide Tetraradical and Diradical: Synthesis, X‐Ray Crystallography, Paramagnetic NMR Spectroscopy, EPR Spectroscopy, and Magnetic Studies.

et al. 2007

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Magnetic resonance relaxivity of dendrimer‐linked nitroxides

Cited by 71 publications

References 37 publications

Relaxivity Studies on Dinitroxide and Polynitroxyl Functionalized Dendrimers: Effect of Electron Exchange and Structure on Paramagnetic Relaxation Enhancement

Relaxivity Studies on Dinitroxide and Polynitroxyl Functionalized Dendrimers: Effect of Electron Exchange and Structure on Paramagnetic Relaxation Enhancement

Reversible reduction of nitroxides to hydroxylamines: Roles for ascorbate and glutathione

1,3‐Alternate Calix[4]arene Nitronyl Nitroxide Tetraradical and Diradical: Synthesis, X‐Ray Crystallography, Paramagnetic NMR Spectroscopy, EPR Spectroscopy, and Magnetic Studies.

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