Design and Synthesis of Aggregation-Induced Emission Photocage Molecules for In Situ Photoactivation Imaging Studies
Received date: 2023-10-19
Online published: 2023-12-27
Supported by
National Natural Science Foundation of China(22067019); National Natural Science Foundation of China(22367023); Yunnan Provincial Science and Technology Department-Yunnan University Joint Special Project(202201BF070001-001); Postgraduate Research Innovation Foundation of Yunnan University(KC-22222295)
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 Caenorhabditis elegans, utilizing a laser confocal imager for cells and a fluorescence microscope for the organism. The findings illustrated the capability of TPA-Tz1 to facilitate in situ photoactivation imaging at both the cellular and in vivo levels in multicellular organisms.
Yu-Qiang Zhao , Xia Zhang , Yunru Yang , Liping Zhu , Ying Zhou . Design and Synthesis of Aggregation-Induced Emission Photocage Molecules for In Situ Photoactivation Imaging Studies[J]. Acta Chimica Sinica, 2024 , 82(3) : 265 -273 . DOI: 10.6023/A23100457
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