Qingfang Li, Chaochao Yan, Peijuan Zhang, Pingxia Wang, Kaige Wang, Wanni Yang, Lin Cheng, Dongfeng Dang, Liping Cao
{"title":"含有辅酶 FAD 的四苯基乙烯基分子笼:面向光催化辅助光动力疗法的同构异构复合物","authors":"Qingfang Li, Chaochao Yan, Peijuan Zhang, Pingxia Wang, Kaige Wang, Wanni Yang, Lin Cheng, Dongfeng Dang, Liping Cao","doi":"10.1021/jacs.4c09508","DOIUrl":null,"url":null,"abstract":"Flavin adenine dinucleotide (FAD), serving as a light-absorbing coenzyme factor, can undergo conformationally isomeric complexation within different enzymes to form various enzyme–coenzyme complexes, which exhibit photocatalytic functions that play a crucial role in physiological processes. Constructing an artificial photofunctional system using FAD or its derivatives can not only develop biocompatible photocatalytic systems with excellent activities but also further enhance our understanding of the role of FAD in biological systems. Here, we demonstrate a supramolecular approach for constructing an artificial enzyme–coenzyme-type host–guest complex with photoinduced catalytic function in water. First, we have designed and synthesized a water-soluble tetraphenylethene (TPE)-based octacationic molecular cage (<b>1</b>) with a large and flexible cavity, which can adaptively encapsulate with two FAD molecules with “U-shaped” conformation (<i>u</i>FAD) to form a 1:2 host–guest complex (<b>1</b>⊃<i>u</i>FAD<sub>2</sub>) in water. Second, based on the conformationally isomeric complexation of FAD within <b>1</b>, the <b>1</b>⊃<i>u</i>FAD<sub>2</sub> complex facilitates electron and energy transfers to molecular oxygen upon the white-light illumination, efficiently producing reactive oxygen species (ROS) such as superoxide radical (O<sub>2</sub><sup>•–</sup>) and singlet oxygen (<sup>1</sup>O<sub>2</sub>). To our knowledge, the <b>1</b>⊃<i>u</i>FAD<sub>2</sub> complex acts as a photocatalyst to achieve the highest turnover frequency (TOF) of 35.6 min<sup>–1</sup> for the photocatalytic oxidation reaction of NADH via a photoinduced superoxide radical catalysis mechanism in an aqueous medium. At last, combining the cytotoxic effects of ROS and the disruption of the intracellular redox balance involving NADH, <b>1</b>⊃<i>u</i>FAD<sub>2</sub> as a supramolecular photosensitizer displays an excellent oxygen-independent photocatalysis-assisted photodynamic therapy in hypoxic tumors.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Tetraphenylethene-Based Molecular Cage with Coenzyme FAD: Conformationally Isomeric Complexation toward Photocatalysis-Assisted Photodynamic Therapy\",\"authors\":\"Qingfang Li, Chaochao Yan, Peijuan Zhang, Pingxia Wang, Kaige Wang, Wanni Yang, Lin Cheng, Dongfeng Dang, Liping Cao\",\"doi\":\"10.1021/jacs.4c09508\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Flavin adenine dinucleotide (FAD), serving as a light-absorbing coenzyme factor, can undergo conformationally isomeric complexation within different enzymes to form various enzyme–coenzyme complexes, which exhibit photocatalytic functions that play a crucial role in physiological processes. Constructing an artificial photofunctional system using FAD or its derivatives can not only develop biocompatible photocatalytic systems with excellent activities but also further enhance our understanding of the role of FAD in biological systems. Here, we demonstrate a supramolecular approach for constructing an artificial enzyme–coenzyme-type host–guest complex with photoinduced catalytic function in water. First, we have designed and synthesized a water-soluble tetraphenylethene (TPE)-based octacationic molecular cage (<b>1</b>) with a large and flexible cavity, which can adaptively encapsulate with two FAD molecules with “U-shaped” conformation (<i>u</i>FAD) to form a 1:2 host–guest complex (<b>1</b>⊃<i>u</i>FAD<sub>2</sub>) in water. Second, based on the conformationally isomeric complexation of FAD within <b>1</b>, the <b>1</b>⊃<i>u</i>FAD<sub>2</sub> complex facilitates electron and energy transfers to molecular oxygen upon the white-light illumination, efficiently producing reactive oxygen species (ROS) such as superoxide radical (O<sub>2</sub><sup>•–</sup>) and singlet oxygen (<sup>1</sup>O<sub>2</sub>). To our knowledge, the <b>1</b>⊃<i>u</i>FAD<sub>2</sub> complex acts as a photocatalyst to achieve the highest turnover frequency (TOF) of 35.6 min<sup>–1</sup> for the photocatalytic oxidation reaction of NADH via a photoinduced superoxide radical catalysis mechanism in an aqueous medium. At last, combining the cytotoxic effects of ROS and the disruption of the intracellular redox balance involving NADH, <b>1</b>⊃<i>u</i>FAD<sub>2</sub> as a supramolecular photosensitizer displays an excellent oxygen-independent photocatalysis-assisted photodynamic therapy in hypoxic tumors.\",\"PeriodicalId\":49,\"journal\":{\"name\":\"Journal of the American Chemical Society\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":14.4000,\"publicationDate\":\"2024-10-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the American Chemical Society\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1021/jacs.4c09508\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the American Chemical Society","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/jacs.4c09508","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Flavin adenine dinucleotide (FAD), serving as a light-absorbing coenzyme factor, can undergo conformationally isomeric complexation within different enzymes to form various enzyme–coenzyme complexes, which exhibit photocatalytic functions that play a crucial role in physiological processes. Constructing an artificial photofunctional system using FAD or its derivatives can not only develop biocompatible photocatalytic systems with excellent activities but also further enhance our understanding of the role of FAD in biological systems. Here, we demonstrate a supramolecular approach for constructing an artificial enzyme–coenzyme-type host–guest complex with photoinduced catalytic function in water. First, we have designed and synthesized a water-soluble tetraphenylethene (TPE)-based octacationic molecular cage (1) with a large and flexible cavity, which can adaptively encapsulate with two FAD molecules with “U-shaped” conformation (uFAD) to form a 1:2 host–guest complex (1⊃uFAD2) in water. Second, based on the conformationally isomeric complexation of FAD within 1, the 1⊃uFAD2 complex facilitates electron and energy transfers to molecular oxygen upon the white-light illumination, efficiently producing reactive oxygen species (ROS) such as superoxide radical (O2•–) and singlet oxygen (1O2). To our knowledge, the 1⊃uFAD2 complex acts as a photocatalyst to achieve the highest turnover frequency (TOF) of 35.6 min–1 for the photocatalytic oxidation reaction of NADH via a photoinduced superoxide radical catalysis mechanism in an aqueous medium. At last, combining the cytotoxic effects of ROS and the disruption of the intracellular redox balance involving NADH, 1⊃uFAD2 as a supramolecular photosensitizer displays an excellent oxygen-independent photocatalysis-assisted photodynamic therapy in hypoxic tumors.
期刊介绍:
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