Amphiphilic aminated fullerenes have a broad margin of safety and significant antitumor effects.Herein,we develop a simple and versatile synthesis strategy for tetraamino-[60]fullerene epoxide(C_(60)(NR^(1)R^(2))_(4)O...Amphiphilic aminated fullerenes have a broad margin of safety and significant antitumor effects.Herein,we develop a simple and versatile synthesis strategy for tetraamino-[60]fullerene epoxide(C_(60)(NR^(1)R^(2))_(4)O)using C_(60)Cl_(6)as a precursor,which notably reduces the reaction time to less than 1 h while retaining a high yield of over 80%with both cyclic and linear secondary amine substrates even at the gram level.The molecular structure of C_(60)(NR^(1)R^(2))_(4)O is first validated by single-crystal diffraction,and a two-step reaction mechanism comprising nucleophilic substitution of Cl and the oxidative elimination of Cl_(2)is proposed based on experimental verification and density functional theory simulation.A set of water-soluble aminated C_(60)(NR^(1)R^(2))_(4)O was prepared in large quantities,and in vitro antitumor evaluation unveiled the critical role that terminal primary amino moieties of C_(60)(NR^(1)R^(2))_(4)O play in their antineoplastic effects.This work provides an effective synthesis method for aminated C_(60)(NR^(1)R^(2))_(4)O,facilitating the development of fullerene-derived tumor-targeted drugs.展开更多
基金supported by the major research project of the National Natural Science Foundation of China(grant no.52272049)the National Key Research and Development Program of China(grant no.2022YFA1205900).
文摘Amphiphilic aminated fullerenes have a broad margin of safety and significant antitumor effects.Herein,we develop a simple and versatile synthesis strategy for tetraamino-[60]fullerene epoxide(C_(60)(NR^(1)R^(2))_(4)O)using C_(60)Cl_(6)as a precursor,which notably reduces the reaction time to less than 1 h while retaining a high yield of over 80%with both cyclic and linear secondary amine substrates even at the gram level.The molecular structure of C_(60)(NR^(1)R^(2))_(4)O is first validated by single-crystal diffraction,and a two-step reaction mechanism comprising nucleophilic substitution of Cl and the oxidative elimination of Cl_(2)is proposed based on experimental verification and density functional theory simulation.A set of water-soluble aminated C_(60)(NR^(1)R^(2))_(4)O was prepared in large quantities,and in vitro antitumor evaluation unveiled the critical role that terminal primary amino moieties of C_(60)(NR^(1)R^(2))_(4)O play in their antineoplastic effects.This work provides an effective synthesis method for aminated C_(60)(NR^(1)R^(2))_(4)O,facilitating the development of fullerene-derived tumor-targeted drugs.
