Design And Synthesis Of Novel Nitroxide Radicals And Research Of Their Performance

Nitroxide radicals are organic compounds with carbon, oxygen, nitrogen, and unpaired electrons. They were first used as spin probes to clarify the structure and function of cell membranes. In recent years, many radicals have been found to have special magnetic and optical properties and bioactivities. As such, much attention has been levied towards the development of these radicals.Nitroxide radicals are one kind of important molecular ferromagnets. Compared with conventional inorganic magnets, they have many advantages, including low density, good light transmittance, strong plasticity, high information storage density, no conductivity, and low magnetic loss. These radicals can be used as magnetic recording materials, magneto-optical devices, and bio-compatible materials, and have potential applications in chemistry, physics, material science and life science.Nitroxide radicals can quench the excited states of fluorophores. Hence, bonding of the nitroxide unit to a fluorescent core will lead to disappearance of fluorescence. When the nitroxide unit is reduced to hydroxylamine by reductant, the fluorescence will reappear. Therefore, the molecules with fluorescent cores and nitroxide receptor units can be used for redox fluorescent switches.It has been proven that some nitronyl nitroxide radicals have anti-radiation and anti-tumor properties and can also combat ischemia reperfusion injury. These special molecules can scavenge harmful radicals in catalytic amount, thereby achieving long-term effects with a small dosage. They have become a hot research area in the development of new drugs.In this thesis, 13 new nitronyl nitroxide radicals were designed and synthesized. The structure and property of these molecules were studied. The detailed contents are as follows:1. Four pairs of sp2 hybridized axially chiral nitronyl nitroxide radicals (R-1~R-4 and S-1~S-4), with dinaphthyl as the basic framework, were designed and synthesized. Their structures were identified by EA, IR, HRMS and ESR. The crystal structures of five nitroxide radicals were measured by X-ray crystal diffraction. CD spectra showed that R-1~R-4 and S-1~S-4 are four pairs of enantiomers.2. The magnetism of the sp2 hybridized axially chiral nitronyl nitroxide radicals R-1, S-1 and R-3, S-3 was examined by variable temperature magnetic susceptibility. The magnetic analysis of R-1 and S-1 revealed that there is weak ferromagnetic interaction between the two spins in the molecules and weak antiferromagnetic interaction between the molecules. The magnetic analysis of R-3 and S-3 revealed that there is weak antiferromagnetic interaction between the molecules. We concluded that there is no magnetic difference between enantiomers of these axially chiral nitronyl nitroxide radicals. 3. We first researched the effect of three reductants and three organic acids on the fluorescence response of nitronyl nitroxide radicals. It was found that the fluorescence quenching effect of the nitroxide unit was dominant, and that the PET effect was subsidiary. More nitroxide receptor units may be beneficial for improving the sensitivity of redox switches.4. We studied the radiation protection of NIT-groups of the axially chiral nitronyl nitroxide radical R-1 and S-1 . The non-toxic dose was obtained by measurement of the cytotoxicity of R-1. and S-1 Radiation protection experiments using L-02 cells showed that R-1 and S-1 exhibited good anti-radiation properties.5. We researched the chiral recognition of nitronyl nitroxide radicals R-1~R-4 and S-1~S-4 on cysteine methyl ester and penicillamine. The results showed that R radicals have better chiral recognition on chiral mercaptan compounds than S radicals.6. One pairs of chiral sp3 hybridized nitronyl nitroxide radicals(L-5,D-5), with tetrahydro-pyrrol as the basic framework, were designed and synthesized. Their structures were identified by EA, IR, HRMS and ESR. The crystal structure of L-5 was measured by X-ray crystal diffraction.7. We studied the anti-cancer activity of NIT-groups of nitronyl nitroxide radicals. The results showed that the nitronyl nitroxide radical L-5 has low toxicity and well water-soluble and better selectivity for inhibiting the growth of normal and tumor cells. The growth inhibition effect on MCF-7 is closed to that of docetaxel. It may become a new anti-tumor lead compound.8. Three achiral nitronyl nitroxide radicals 6-8 were designed and synthesized. Their crystal structures were measured by X-ray crystal diffraction. The properties of these radicals are being investigated. 9. New polar-modified phases were synthesized and characterized. Compared to conventional C18 phases, polar-modified phases are more suitable under highly aqueous mobile phase conditions. Polar-modified phases provide unique selectivity with good separation. At the same time, they can decrease the interaction between basic compounds and residual silanols on the silica gel surface and demonstrate good peak shapes. The polar-modified phases can separate the reaction intermediates of nitronyl nitroxide radicals effectively. This study provided the experimental data and theoretical basis for further research on developing new drugs of anti-radiation and anti-tumor and new kinds of NIT nitronyl nitroxide radicals.