Development of novel nitroxyl radicals for controlling reactivity with ascorbic acid

Abstract

Piperidine and pyrrolidine nitroxyl radicals (nitroxide) contain unpaired electrons and have been widely recognized as antioxidants, contrast agents, spin probes, radiation protective agents and polymerization mediators. Nitroxyl radicals can react with free radicals and reductants and their reactivities depend on the basic structure of the nitroxyl radicals themselves. However, reductants easily reduce these radicals and they lose their paramagnetic nature and function. Therefore, the aim of this study was to develop various functional nitroxyl radicals, particularly focusing on stability towards AsA through the improvement of the synthetic route for a series of 2,6-substituted nitroxyl radicals. Tetraethyl-substituted piperidine nitroxyl radical 8 exhibited resistance to AsA reduction and 2,6-dispiro-4',4''-dipyrane-piperidin-4-one-N-oxyl 5 had a second-order rate constant 10-times greater than those of hydroxyl-TEMPO and oxo-TEMPO. The 2,6-substituted compound offers various reactivities towards AsA and the possibility to be used as a new antioxidant, contrast agent and radical polymerizer.

Synthesis and Utilization of α-Substituted Nitroxides

“…Although piperidine nitroxides with spirocyclohexyl groups at -positions showed no difference in reactivity with ascorbic acid, the enzymatic reaction was efficiently protected (Okazaki et al, 2007). Recently, tetraethyl-substituted piperidine nitroxide was also reported to exhibit resistance to ascorbate reduction (Kinoshita et al, 2009). The electron spin resonance (ESR) or electron paramagnetic resonance (EPR) signal intensities of tetraethyl-substituted piperidine nitroxide remained 97% after ascorbate addition (Fig.…”

“…Copyright (2012) American Chemical Society. (Kinoshita et al, 2009). This suggests that the electronic environment around the N-O moiety also influences its reduction stability.…”

Comparative Study of the Reduction Process of Different Ring Structured Nitroxyl Spin Probes: An Electron Spin Resonance Study

“…The most active use of invivo ESR spectroscopy and its imaging has been in the measurement of redox status, radical generation and partial pressure of oxygen. ESR spectroscopy has been employed in invitro redox research studies [12,13]. In the ESR X-band frequency the magnetic interactions of nitroxide spin labels are extremely sensitive to motion on the nanosecond time scale, which is relevant to the dynamics of bio-molecules [14].…”

Synthesis and Reduction Kinetics of Five Ibuprofen–Nitroxides for Ascorbic Acid and Methyl Radicals

“…[9][10][11] The rate constants of them are greatly different and could not measure under the same conditions. 9,10,17) For the nitroxides resistant to AsA, we planned to examine the measurement of their rate constants using methyl radicals formed by Fenton reaction. The balance between their sensitivity for reductants and half-life is important for use of nitroxide as an in-vivo probe.…”

“…They had different reduction rates for reductants such as ascorbic acid (AsA), and these were applied as an invivo probe. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] The rate constant of reduction of a nitroxide probe in vitro is expected to be a guideline of its half-life in vivo. [9][10][11] The rate constants of them are greatly different and could not measure under the same conditions.…”