聚集诱导发射光笼分子的设计合成及原位光激活成像研究  

Design and Synthesis of Aggregation-Induced Emission Photocage Molecules for In Situ Photoactivation Imaging Studies

作　　者：赵玉强 张霞[1] 杨芸如 朱立平 周莹 Yu-Qiang Zhao;Xia Zhang;Yunru Yang;Liping Zhu;Ying Zhou(College of Chemical Science and Technology,Yunnan University,Kunming 650091,China)

机构地区：[1]云南大学化学科学与工程学院,昆明650091

出　　处：《化学学报》2024年第3期265-273,共9页Acta Chimica Sinica

基　　金：国家自然科学基金(Nos.22067019,22367023);云南省科技厅-云南大学联合特殊项目(No.202201BF070001-001);云南大学研究生研究创新基金(No.KC-22222295)资助。

摘　　要：通过将1,2,4,5-四氮嗪基团引入到聚集诱导发射(AIE)荧光团上,制备了两个光激活的荧光小分子化合物TPA-Tz1和TPA-Tz2.光激活后, TPA-Tz1和TPA-Tz2的荧光强度分别增强了167倍和100倍.光激活的原理是光照导致四氮嗪基团转化为氰基,从而恢复荧光发射.通过密度泛函理论(DFT)计算,TPA-Tz1的猝灭机理为能量转移至暗态(ETDS). TPA-Tz1的激活产物TPA-CN1具有独特的AIE特点,其聚集态分子间发生的电荷转移是导致聚集态荧光蓝移的主要原因.通过溶剂挥发法获得的TPA-Tz1晶体结构揭示了其内部复杂的堆叠结构,氢键和C—H…π作用代替π-π相互作用是同时维持晶格稳定和AIE特性的重要原因.TPA-Tz1具有良好的生物相容性,其最高的细胞抑制率仅有25.3%.因此, TPA-Tz1在细胞水平和多细胞生物秀丽隐杆线虫体内实现了原位的光激活成像.Two photoactivated fluorescent small molecule compounds, TPA-Tz1 and TPA-Tz2, were synthesized by incorporating a 1,2,4,5-tetrazine group into an aggregation-induced emission (AIE) fluorogen. Upon continuous UV light exposure, the fluorescence intensity of TPA-Tz1 and TPA-Tz2 increased by 167-fold and 100-fold, respectively. The photoactivation mechanism of the TPA-Tz1 solution was confirmed using high-resolution mass spectrometry, both before and after illumination, as part of standard verification procedures. The photoactivation mechanism involves the conversion of the tetrazine group to the cyanide group upon light exposure, leading to the restoration of fluorescence emission. Density functional theory (DFT) calculations revealed that the quenching mechanism of TPA-Tz1 involves energy transfer to dark states (ETDS). The fluorescence assessment of photoactivated TPA-CN1 products in solutions with varying water contents revealed distinct AIE characteristics. Specifically, a decline in fluorescence was evident at water contents below 50%, attributable to the twisted intramolecular charge transfer (TICT) effect. Conversely, as water content increased from 60% to 95%, a conspicuous blue shift and enhanced fluorescence were observed. Analysis of the excited states of its dimer, employing time-dependent density functional theory (TDDFT) hole charge analysis, underscored that charge transfer within the aggregated state predominantly accounted for the observed blue shift. The crystal structure of TPA-Tz1, obtained using a solvent evaporation method, unveiled its intricate internal stacked structure. The replacement of π-π interactions by hydrogen bonds and C—H…π interactions played a crucial role in maintaining both lattice stability and AIE. Moreover, cytotoxicity assessments conducted across diverse cell lines demonstrated the biocompatibility of TPA-Tz1, revealing a maximum cell inhibition rate of only 25.3%. Ultimately, photoactivated fluorescence imaging experiments were conducted on cells and Caenorhabditi

关 键 词：光笼 聚集诱导发光 密度泛函理论 光激活荧光 荧光成像 

分 类 号：O657.3[理学—分析化学] Q503[理学—化学]