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

项目概要/摘要 该提案描述了利用基本化学性质来改变试剂的反应性 生物医学上重要的化合物的合成。具体来说，C-S键的化学性质为 用于合成名为供体-受体 Stenhouse 加合物 (DASA) 的新型光开关。虽然 Stenhouse 加合物于 2014 年推出，在药物输送、动态相转移、 聚合物、液晶、选择性光开关和化学传感应用。尽管他们充满希望 DASA 目前的应用受到其结构多样性的限制。只有胺供体和两个受体 目前通常用于 DASA 系统。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 间隙使得新开发的分子可以在 650–1450 nm 的生物窗口内被激活 光。这样做将光可切换分子置于具有挑战性的光药理学和特异性领域 发光应用。具体来说，DASA 光电开关具有从线性、不带电到 环状两性离子中间体的结构提供了渗透血脑屏障的机会 开发有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、氧的加合物以及其他共轭 将被调查。 2-噻吩甲醛具有更弱且更长的 C-S 键代替 C-O 键 当使用糠醛作为起始原料时，无法将其他供体功能纳入 DASA 中 材料；噻吩衍生物的碳原子上的电子密度也较低，使其成为完美的底物 用于在缩合受体分子时开环。如果 C-S 键不够弱，可极化 硫将使用亲硫性路易斯酸活化。合成新型 Stenhouse 加合物 1) 提供了额外的 DASA 探索上述应用，2) 能够进一步研究这些新材料的化学性质 光开关，3) 提供了开发其他用途的机会，例如光药理学中列出的用途 和光发射应用。

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.