具有聚集诱导发光性质的高效热激活延迟荧光材料用于脂滴成像

doi:10.6023/cjoc202403038

摘要/Abstract

具有聚集诱导发光(AIE)性质的热激活延迟荧光(TADF)材料可作为染料标记物用于无自体荧光的生物成像. 然而, 可特异性靶向至脂滴并进行高质量荧光成像的高效AIE-TADF染料目前极少有报道. 通过在邻苯二甲酰亚胺单元上分别引入二苯胺、9,10-二氢-9,9-二苯基吖啶、9,10-二氢-9,9-二甲基吖啶等结构不同的电子给体以及连接脂滴靶向基团吗啉, 成功获得了三个新型的有机发光分子. 研究发现, 所合成的化合物均表现出优异的AIE性能, 其在固态下的荧光量子产率可达46.5%. 同时, 5-(二苯胺基)-2-(2-吗啉基乙基)异吲哚啉-1,3-二酮(1)和5-(9,9-二苯基吖啶-10(9H)-基)-2-(2-吗啉基乙基)异吲哚啉-1,3-二酮(2)只能产生荧光, 而5-(9,9-二甲基吖啶-10(9H)-基)-2-(2-吗啉基乙基)异吲哚啉- 1,3-二酮(3)则可以发射高亮度的TADF. 更重要的是, 3不仅具有良好的生物相容性, 而且可以进入细胞并特异性靶向至脂滴, 从而实现高亮度的荧光成像. 其与商用脂滴染色剂Bodipy的成像区域的Pearson相关系数高达0.87. 该工作为用于生物成像的高性能AIE-TADF分子的开发提供了新的思路.

关键词: 聚集诱导发光, 热激活延迟荧光, 脂滴, 生物成像

Thermally activated delayed fluorescence (TADF) materials with aggregation-induced emission (AIE) properties are promising for autofluorescence-free bioimaging. However, efficient AIE-TADF luminogens that can specifically target lipid droplets and enable high-quality fluorescence imaging are very limited. 3 new organic luminophores were successfully developed by introducing diphenylamine, 9,10-dihydro-9,9-diphenylanthracene, and 9,10-dihydro-9,9-dimethylanthracene, respectively, onto the phthalimide moiety, along with a lipid droplet-targeting group, morpholine. These compounds exhibited excellent AIE properties with fluorescence quantum yields up to 46.5% in the solid state. Moreover, 5-(diphenylamine)- 2-(2-morpholinoethyl)isoindoline-1,3-dione (1) and 5-(9,9-diphenylacridine-10(9H)-yl)-2-(2-morpholinoethyl) isoindoline-1,3- dione (2) only displayed prompt fluorescence, while 5-(9,9-dimethylacridine-10(9H)-yl)-2-(2-morpholinoethyl)isoindoline- 1,3-dione (3) demonstrated intense TADF. More importantly, 3 exhibited good biocompatibility and the ability to enter cells and specifically target lipid droplets, enabling high-brightness fluorescence imaging. The Pearson’s correlation coefficient between 3 and the commercially available lipid droplet dye Bodipy reached 0.87 in the imaging area. This work provides a new approach for the development of high-performance AIE-TADF molecules for bioimaging applications.

Key words: aggregation-induced emission, thermally activated delayed fluorescence, lipid droplet, bioimaging

引用此文

黄凯航, 尹理, 姜青云, 汪乾, 石光, 许炳佳. 具有聚集诱导发光性质的高效热激活延迟荧光材料用于脂滴成像[J]. 有机化学, 2024, 44(8): 2479-2486.

Kaihang Huang, Li Yin, Qingyun Jiang, Qian Wang, Guang Shi, Bingjia Xu. Efficient Thermally Activated Delayed Fluorescence Materials with Aggregation-Induced Emission for Lipid Droplet Imaging[J]. Chinese Journal of Organic Chemistry, 2024, 44(8): 2479-2486.

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图/表 7

图式1. 化合物的合成线路图

Scheme 1. Synthetic routs to the target compounds

图1. 化合物1、2和3在(a)四氢呋喃中和(b)固态下的荧光发射光谱(溶液浓度: 0.1 mmol/L; 激发波长: 330 nm)

Figure 1. PL spectra of 1, 2 and 3 in (a) tetrahydrofuran (THF) and (b) solid state (concentration: 10 μmol/L; excitation: 330 nm)

图2. (a) 3在不同含水量的水/二甲基亚砜混合溶液中的荧光发射(PL)光谱(插图是3在365 nm紫外光照射下于纯二甲基亚砜和水的体积分数为99%的水/二甲基亚砜混合溶液中的荧光照片)及(b) 3在不同含水量的水/二甲基亚砜混合溶液中的紫外-可见吸收光谱(浓度: 50 μmol/L)

Figure 2. (a) PL spectra of 3 in the water/DMSO mixtures with different water fractions (the insets are the fluorescence images of 3 in pure DMSO and water/DMSO mixture with 99% water fraction under the illumination of 365 nm UV light) and (b) UV-vis absorption spectra of 3 in the water/DMSO mixtures with different water fractions (concentration: 50 μmol/L)

Compd.	λ_abs,sl^a/nm	λ_em,sl^b/nm	λ_em,s^c/nm	τ_flu.^d/ns	τ_TADF^e/μs	Φ_PL,s^f/%	α_AIE^g	ΔE_ST^h/eV
1	396	548	519	11.26	N/A	24.1	42.6	0.59
2	390	606	540	14.65	N/A	24.0	130.9	0.18
3	394	640	547	47.60	4.60	46.5	57.8	0.05

表1. 化合物1、2和3的一些重要光物理参数

Table 1. Some important photophysical parameters of 1, 2, and 3

图3. (a)化合物3的固体粉末在室温下于真空和空气中的发光衰减曲线及(b)化合物3的固体粉末在真空中于不同温度下的发光衰减曲线

Figure 3. (a) Emission decay curves for the solid powder of 3 at room temperature under vacuum and in the air and (b) emission decay curves for the solid powder of 3 at different temperatures under vacuum

图4. A549 癌细胞与不同浓度的3纳米聚集体共孵育4 h后的存活率(用CCK-8 法测定)

Figure 4. Viability of A549 cancer cells after incubating with different concentrations of 3 nanoaggregates for 4 h (by CCK8 assay)

图5. 3对A549细胞的激光扫描共聚焦显微镜(LSCM)荧光成像图(浓度: 10 μmol/L; 激发波长: 405 nm)

Figure 5. LSCM images of 3 in A549 cancer cells (concentration: 10 μmol/L; excitation: 405 nm) (a) Fluorescent image of the lipid droplets stained by Bodipy (green pseudocolor), (b) fluorescent image of the lipid droplets stained by 3 (yellow pseudocolor), and (c) an overlay image of parts a and b.

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