{"title":"A Simple Synthesis of Tetraamino-[60]Fullerene Epoxides as Potential Antitumor Drug Candidates","authors":"Yicheng Lu, Jie Li, Xiaolong Liu, Dan He, Libin Yang, Wei Zhou, Xie Wang, Shanshan Chen, Shiliang Chen, Yating Liu, Xin Wang, Jiao Li, Jiawei Huo, Yang Liu, Zehu Wang, Meihan Liu, Yijun Wang, Yamin Li, Fuwen Zhao, Shumu Li, Jinchao Wei, Jianan Liu, Wei Li, Chunru Wang","doi":"10.31635/ccschem.024.202303784","DOIUrl":null,"url":null,"abstract":"<p>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<sub>60</sub>(NR<sup>1</sup>R<sup>2</sup>)<sub>4</sub>O) using C<sub>60</sub>Cl<sub>6</sub> 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<sub>60</sub>(NR<sup>1</sup>R<sup>2</sup>)<sub>4</sub>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<sub>2</sub> is proposed based on experimental verification and density functional theory simulation. A set of water-soluble aminated C<sub>60</sub>(NR<sup>1</sup>R<sup>2</sup>)<sub>4</sub>O was prepared in large quantities, and <i>in vitro</i> antitumor evaluation unveiled the critical role that terminal primary amino moieties of C<sub>60</sub>(NR<sup>1</sup>R<sup>2</sup>)<sub>4</sub>O play in their antineoplastic effects. This work provides an effective synthesis method for aminated C<sub>60</sub>(NR<sup>1</sup>R<sup>2</sup>)<sub>4</sub>O, facilitating the development of fullerene-derived tumor-targeted drugs.</p>","PeriodicalId":9810,"journal":{"name":"CCS Chemistry","volume":null,"pages":null},"PeriodicalIF":9.4000,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CCS Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.31635/ccschem.024.202303784","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
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 (C60(NR1R2)4O) using C60Cl6 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 C60(NR1R2)4O is first validated by single-crystal diffraction, and a two-step reaction mechanism comprising nucleophilic substitution of Cl and the oxidative elimination of Cl2 is proposed based on experimental verification and density functional theory simulation. A set of water-soluble aminated C60(NR1R2)4O was prepared in large quantities, and in vitro antitumor evaluation unveiled the critical role that terminal primary amino moieties of C60(NR1R2)4O play in their antineoplastic effects. This work provides an effective synthesis method for aminated C60(NR1R2)4O, facilitating the development of fullerene-derived tumor-targeted drugs.
期刊介绍:
CCS Chemistry, the flagship publication of the Chinese Chemical Society, stands as a leading international chemistry journal based in China. With a commitment to global outreach in both contributions and readership, the journal operates on a fully Open Access model, eliminating subscription fees for contributing authors. Issued monthly, all articles are published online promptly upon reaching final publishable form. Additionally, authors have the option to expedite the posting process through Immediate Online Accepted Article posting, making a PDF of their accepted article available online upon journal acceptance.