Polymer Chelator Prepared via the Kabachnik-Fields Reaction for the In Vivo Prevention of Heavy-Metal Damage
Polymer Chelator Prepared via the Kabachnik-Fields Reaction for the In Vivo Prevention of Heavy-Metal Damage
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DOI：
10.1021/acs.chemmater.2c02074
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发表时间：
2022-10-21
影响因子：
8.6
通讯作者：
Tao, Lei
中科院分区：
文献类型：
--
作者：
He, Xianzhe;Yang, Lei;Tao, Lei
重金属中毒是一个全球性的问题，因此，安全有效的螯合剂对急性和慢性重金属中毒是至关重要的公共卫生。在这里，我们开发了一种策略，探索聚合物螯合剂的重金属中毒相结合的Kabachnik-Fields反应和聚合物化学。得到了一种具有一定金属螯合能力和抗氧化能力的水溶性聚合物。在体内实验中，该聚合物可有效预防目前尚无有效解毒剂的小鼠急性和慢性镉中毒，其预防效果明显上级临床常用药物2，3-二巯基丙磺酸钠盐和依地酸钙二钠。详细的研究表明，这种聚合物螯合剂的优点源于其优异的安全性和长的代谢寿命。本研究通过多组分反应探索了功能聚合物，并产生了用于防止重金属中毒的聚合物螯合剂，这为指导用于体内应用的聚合物材料的设计提供了潜在的见解。
Heavy-metal poisoning is a global concern; therefore, safe and efficient chelators against acute and chronic heavy-metal poisoning are vital for public health. Here we developed a strategy to explore polymer chelators for heavy-metal poisoning by combining the Kabachnik-Fields reaction and polymer chemistry. A water-soluble polymer with considerable metal-chelating ability and antioxidant capability was obtained. During in vivo experiments, this polymer effectively prevented acute and chronic cadmium poisoning in mice for which there is no efficient antidote; the prevention effect was significantly superior to clinically available drugs, 2,3-dimercaptopropanesulfonic acid sodium salt and calcium disodium edetate. Detailed studies revealed that the advantages of this polymer chelator originate from its excellent safety and long metabolic life. This study explored functional polymers via a multicomponent reaction and yielded a polymer chelator for preventing heavy-metal poisoning, which provides underlying insights to guide the design of polymer materials for in vivo applications.