Synthesis and Characterization of Nitrogen and Sulfur Donor-Acceptor Stenhouse Adducts

氮和硫供体-受体 Stenhouse 加合物的合成与表征

• 批准号: 10724739
• 负责人: Elias Picazo
• 金额: $ 8.85万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10724739
• 关键词: Acids; Affinity; Alcohols; Amines; Area; Biological; Blood - brain barrier anatomy; Carbohydrates; Carbon; Characteristics; Chemistry; Drug Delivery Systems; Electrons; Fluorescence; Foundations; Future; Glycosides; Goals; Health; Human; Hydrogen; Hydrogen Bonding; In Vitro; Instruction; Learning; Light; Medical; Modification; Molecular Conformation; Names; Nature; Nitrogen; Oxygen; Periodicity; Pharmaceutical Preparations; Phase; Phosphines; Phosphorus; Polymers; Progress Reports; Property; Reagent; Research; Solubility; Solvents; Structure; Sulfhydryl Compounds; Sulfur; Surface; System; Thiophenes; Triplet Multiple Birth; Update; adduct; blood-brain barrier crossing; catalyst; chemical property; electron density; experience; functional group; improved; interest; light emission; liquid crystal; novel; physical property; pi bond; programs; restraint; single bond; trend

Project Summary/Abstract This proposal describes the use of fundamental chemical properties to alter the reactivity of reagents for the synthesis of biomedically important compounds. Specifically, the chemical properties of C–S bonds will be used for the synthesis of novel photoswitches named donor-acceptor Stenhouse adducts, DASAs. Though Stenhouse adducts were introduced in 2014, they have been explored in drug delivery, dynamic phase transfer, polymers, liquid crystals, selective photoswitching, and chemosensing applications. Despite their promising applications, DASAs are currently limited by their structural diversity. Only amine donors and two acceptors are generally used in DASA systems today. As a result, the physical properties and applications are limited. The overarching goal is to develop and characterize novel DASA molecules with a narrow HOMO-LUMO gap such that the newly developed molecules may be activated within the biological window of 650–1450 nm light. Doing so puts photoswitchable molecules into the realm of challenging photopharmacological and specific light-emission applications. Specifically, the unique ability for DASA photoswitches to go from linear, uncharged structures to cyclic, zwitterionic intermediates presents an opportunity to permeate the blood-brain barrier and to develop interesting thermally activated delayed fluorescence (TADF) species. In order to access new DASA molecules with the desired characteristics, adducts with sulfur, phosphine, oxygen, and additional conjugation will be investigated. 2-Thiophenecarboxaldehyde bears a weaker and longer C–S bond in place of the C–O bond responsible for the inability to incorporate other donor functionality in DASAs when using furfural as a starting material; thiophene derivatives also carry less electron density on the carbon atoms, making it a perfect substrate for ring opening upon condensing an acceptor molecule. If the C–S bond is not sufficiently weak, the polarizable sulfur will be activated using thiophilic Lewis acids. Synthesizing novel Stenhouse adducts 1) provides additional DASAs to explore applications listed above, 2) enables further research on the chemical properties of these new photoswitches, and 3) provides an opportunity to develop additional uses like those listed in photopharmacology and light emission applications.

项目总结/摘要 该提案描述了使用基本化学性质来改变试剂的反应性， 生物医学上重要化合物的合成。具体来说，C-S键的化学性质将是 用于合成新的光开关，命名为供体-受体Stenhouse加合物，DASA。虽然 Stenhouse加合物于2014年引入，它们已在药物递送，动态相转移， 聚合物、液晶、选择性光开关和化学传感应用。尽管他们承诺 然而，在实际应用中，DASA目前受到其结构多样性的限制。只有胺供体和两个受体是 目前在DASA系统中普遍使用。因此，其物理性能和应用受到限制。 总体目标是开发和表征具有窄HOMO-LUMO的新型DASA分子 使得新开发的分子可以在650-1450 nm的生物窗口内被激活 光这样做使光开关分子进入具有挑战性的药理学和特异性的领域。 发光应用。具体来说，DASA光电开关的独特能力， 环状两性离子中间体的结构提供了渗透血脑屏障的机会， 开发感兴趣的热激活延迟荧光（TADF）物种。为了访问新的DASA 具有所需特性的分子，与硫、膦、氧的加合物，以及额外的共轭 将被调查。2-噻吩甲醛带有一个较弱和较长的C-S键代替C-O键 当使用糠醛作为起始原料时， 噻吩衍生物在碳原子上携带的电子密度也更低，使其成为完美的基底 用于在缩合受体分子时开环。如果C-S键不够弱，则可极化的 硫将使用亲硫刘易斯酸活化。合成新型Stenhouse加合物1）提供了额外的 DASA探索上面列出的应用，2）使进一步研究这些新的化学性质 光开关，和3）提供了一个机会，开发额外的用途，如那些列在药理学 和发光应用。