Synthesis,Preparation And Study Of Fullerene Pyrrolidine And Its Doxorubicin Derivatives

The special cage structure of fullerene gives it many excellent properties,but the hydrophobicity of fullerene limits its application to biological systems.Therefore,increasing the water solubility of fullerene can broaden its application prospect in biomedical applications such as anti-tumor,anti-microbial and free radical scavenging.Chemical modification of fullerene can introduce a reactive group while improving water solubility to obtain a fullerene pyrrolidine derivative which can be further used to synthesize more kinds of fullerene derivatives due to carrying a reactive group such as hydroxyl group and carboxyl group.Doxorubicin is a broad-spectrum anti-tumor drug that has a good effect on tumor treatment,but it will produce free radical-mediated side effects on the body.so it is necessary to introduce fullerene to attenuate this side effect.Based on the above,this paper has carried out the following research work: Firstly,Synthesis of N-substituted 3,4-fullerene pyrrolidine(FP-OH)and carboxypropyl fullerene pyrrolidine(FP-COOH)with improved water solubility and reactive groups;Secondly,Fullerene glycine(FP-Gly)was synthesized on the basis of FP-OH and then noncovalently compounded with doxorubicin to form fullerene glycine/doxorubicin complex(FP-Gly/DOX);Thirdly,On the basis of FP-COOH,it is linked with doxorubicin by amidation reaction to synthesize fullerene pyrrolidine doxorubicin(FP-COOH-DOX);The five fullerene derivatives obtained above were made into a nano-aqueous suspension,and the free radical effect of each nano-aqueous suspension under dark and light conditions was tested.The research results obtained are as follows:1.FP-OH,FP-COOH,FP-Gly and FP-COOH-DOX were successfully synthesized,and their structures were confirmed by UV-vis,FT-IR and MALDI-TOF characterization,and FP-Gly/DOX was prepared by physical stirring method.2.The obtained fullerene derivative was made into a 20 ?mol/L nano-aqueous suspension by organic solvent-mediated method,and the particle size distribution of the FP-COOH nano-suspension was measured.The results showed that the distribution range was 36.52-121.37 nm,D(90%)is 50.43 nm,indicating that the FP-COOH nanoparticles have an ideal nanometer size.3.Through the pyrogallol autooxidation experiment,it was found that in the dark conditions,compared with the same concentration of VC,the prepared fullerene derivative nano-suspension has the ability to scavenge superoxide anion radicals,from weak to strong: FP-OH < FP-COOH < VC < FP-Gly < FP-Gly/DOX < FP-COOH-DOX.4.The methyl violet-Fenton system experiment showed that the prepared nano-water suspensions of fullerene derivatives had the ability to scavenge hydroxyl radicals under dark conditions,and the scavenging ability is stronger than 5 mmol/L mannitol,from weak to strong: FP-OH < FP-COOH < FP-Gly < FP-Gly/DOX < FP-COOH-DOX,wherein 50 mmol/L of mannitol is close to the FP-Gly/DOX scavenging efficiency.Using the methyl violet system,it is found that under the light condition,the prepared fullerene derivative nano-suspension has the ability to generate hydroxyl radicals,from weak to strong: FP-OH < FP-COOH < FP-COOH-DOX < FP-Gly < FP-Gly/DOX.The results showed that the five fullerene derivatives synthesized in this paper have strong free radical scavenging ability.Two fullerene pyrrolidines and fullerene glycine derivatives can be used as intermediates to further synthesize other fullerene derivatives,and two types of fullerene doxorubicin derivatives can be a new low-toxic anti-tumor drug.