Synthesis and Reduction Kinetics of Sterically Shielded Pyrrolidine Nitroxides

Abstract

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.

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

“…Synthesis Six nitroxides (6)(7)(8)(9)(10)(11) were synthesized by the synthetic methods shown in Chart S1. Sterically shielded nitroxides 7, 10 and 11 were synthesized according to the method established by Yamada's group [4][5][6][7] and Rajca's group.…”

“…Sterically shielded nitroxides 7, 10 and 11 were synthesized according to the method established by Yamada's group [4][5][6][7] and Rajca's group. [9][10][11] Since there were some low-yield reaction steps in the synthesis of the sterically shielded nitroxides (7, 10, 11), the reaction conditions were partially improved and synthesis was achieved.…”

“…[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. 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.…”

“…[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.…”

Synthesis of Novel Nitroxide Radical Polymer Materials for Imaging and Energy Storage Applications

“…One is to make the nitroxide inherently more stable towards reduction by tuning its molecular substitution pattern, providing more steric hindrance and thus restricting access of reducing agents to the radical itself, prolonging its lifetime. 317 Another option is to incorporate the nitroxides into larger macromolecular architectures. This achieves two things: (a) it allows an increase to the local concentration of nitroxides while keeping the overall concentration of injected contrast agent at minimum required levels; and (b) the macromolecular architecture, which can be tailored to specific needs, provides an easily tuneable protective shield by restricting access to the nitroxides.…”