基于AIE机理的Cys/HCy高选择性荧光探针设计

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"Bioorganic Chemistry: 王鹏课题组、陈俊青课题组设计的基于聚集诱导发光(AIE, Aggregation-Induced Emission)机理的高荧光选择性鉴定Cys(胱氨酸)/HCy(同型半胱氨酸)的荧光探针" 在生物有机化学领域，王鹏课题组与陈俊青课题组共同设计了一种新型的荧光探针SQM-NBD，其特别之处在于利用了聚集诱导发光(AIE)现象来实现对Cys和HCy的高度选择性检测。这种探针对于维持体内平衡及关联多种疾病的Cys和HCy具有重要意义，因为它们在活体系统中的浓度远低于谷胱甘肽(GSH)，因此在大量GSH存在下识别Cys和HCy是一个重大挑战。文章关键词包括：荧光探针、胱氨酸、同型半胱氨酸、AIE效应、荧光成像。这表明研究的核心是开发一种荧光探针，它能够通过荧光信号的变化来特异性地识别Cys和HCy，而不会被GSH等其他生物分子干扰。文章摘要指出，探针SQM-NBD是通过将NBD(萘二甲酸二乙酯)连接到荧光团SQM-OH的羟基上得到的。这种设计巧妙地利用了AIE效应，通常情况下，某些荧光分子在溶液中单独存在时并不发光，但当它们聚集或形成固态时，反而能显著增强其荧光发射。在探针SQM-NBD中，这一特性使得探针在遇到目标分子Cys或HCy时，能发生特定的化学反应，导致其结构改变并产生荧光增强，从而实现高灵敏度和选择性的检测。荧光成像技术是该探针应用的重要手段，通过荧光信号的变化，研究人员可以在细胞和组织水平上实时监测Cys和HCy的动态变化，这对于理解它们在生物体系中的作用和疾病相关过程有重大价值。例如，过高的Cys和HCy水平可能与心血管疾病、神经退行性疾病和其他代谢障碍有关。王鹏课题组和陈俊青课题组的这项工作不仅展示了创新的荧光探针设计策略，还为生物分析和医学诊断提供了新的工具，有助于在复杂生物环境下的Cys和HCy检测，从而促进相关疾病的早期诊断和治疗。

Bioorganic Chemistry 126 (2022) 105902

Available online 24 May 2022

Highly selective uorescent probe based on AIE for identifying cysteine/

homocysteine

Wei Wang

, Zihao Peng

, Min Ji

, Junqing Chen

, Peng Wang

School of Chemistry and Chemical Engineering, Southeast University, Nanjing, Jiangsu 211189, PR China

School of Biological Science & Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, PR China

School of Engineering, China Pharmaceutical University, Nanjing 210009, PR China

ARTICLE INFO

Keywords:

Fluorescent probe

Cysteine

Homocysteine

AIE

Fluorescence imaging

ABSTRACT

Cysteine (Cys) and homocysteine (Hcy) are involved in maintaining homeostasis in the body and are relevant to

various diseases. While the level of Cys and Hcy is much lower than GSH in the living system, which leads to a

major challenge to selectively identify Cys/Hcy in the presence of large amounts of GSH. In this paper, an AIE

uorescent probe SQM-NBD was obtained by connecting NBD to the hydroxyl group of the uorophore SQM-OH

for selective detection of Cys/Hcy. Probe SQM-NBD had no uorescence itself. But, under the disturbance of

GSH, the uorescence signal of probe SQM-NBD could be turned on by Cys/Hcy. The study of the response

mechanism showed that probe SQM-NBD could release both SQM-OH and Cys/Hcy-NBD after reacting with Cys/

Hcy. While Cys/Hcy continued to quench the uorescence of SQM-OH through the combination of Michael

addition and the ion rich environment, resulting in only the uorescence signal of Cys/Hcy-NBD being observed.

SQM-NBD appeared superior sensitivity to Cys/Hcy, with LOD of 54 nM and 72 nM, respectively. Signicantly,

probe SQM-NBD realized the application of uorescence imaging of Cys/Hcy in HeLa cells, indicating that probe

SQM-NBD has the potential for Cys/Hcy identication under physiological and pathological conditions.

1. Introduction

Biothiols such as cysteine (Cys), homocysteine (Hcy), and gluta-

thione (GSH) play important roles in maintaining the Redox and phys-

iological balance in the living system [1]. Among them, Cys is an

important antioxidant that can protect cells from oxidative damage. It

can coordinate with a variety of heavy metals to relieve heavy metal

poisoning [2–4]. Moreover, the loss of Cys can lead to many diseases

including slow growth, hair decoloration, muscle and fat loss, and skin

damage in children [5–7]. Hcy is involved in the DNA synthesis and

methylation in organisms and is also closely related to cardiovascular

diseases. Even slight uctuations in the Hcy level may contribute to the

development of cardiovascular diseases [8–10]. Due to the distinctive

physiological properties of Cys/Hcy, it is imperative to explore tech-

niques for Cys/Hcy detection. However, since the molecular structure

and properties of Cys/Hcy bear a strong resemblance to GSH, and the

content of Cys/Hcy is much lower than that of GSH, the detection of

Cys/Hcy is highly susceptible to the disturbance of GSH [11–13].

Therefore, the development of methods that can selectively detect Cys/

Hcy under GSH disturbance is a great challenge.

In recent years, organic small-molecule uorescent probes have been

widely used in the detection of Cys/Hcy with convenience and effec-

tiveness. Detection mechanisms include Michael addition [14], sulfon-

amide and sulfonate cleavage [15], disulde exchange [16], conjugated

addition cyclization [17], aldehydes cyclization [18], mercaptan

halogen nucleophilic substitution [19], and metal complex replacement

coordination [20]. However, the applications of most developed uo-

rescence probes in the aqueous environment are limited due to the

aggregation-induced quenching (ACQ) effect [21–23]. In contrast, the

AIE effect, rst reported by the Tang group, could effectively overcome

this shortcoming. Unlike ACQ uorophore, AIE uorophore shows

strong uorescence when molecules gather together [24–25]. In addi-

tion, AIE uorophore is characterized by low background noise, high

signal-to-noise ratio (SNR), high brightness, and good photostability,

which is conducive to uorescence imaging of Cys/Hcy in living cells

[26–29].

In this paper, probe SQM-NBD was produced using

ethylenethiophenol-modied quinoline-malononitrile SQM-OH as uo-

rophore and 7-nitro-2,1,3-benzoxadiazole (NBD) as recognition section.

The recognition group NBD has been widely used for the selective

* Corresponding authors.

E-mail addresses: jqchen@seu.edu.cn (J. Chen), wangpeng@cpu.edu.cn (P. Wang).

Contents lists available at ScienceDirect

Bioorganic Chemistry

journal homepage: www.elsevier.com/locate/bioorg

https://doi.org/10.1016/j.bioorg.2022.105902

Received 26 April 2022; Received in revised form 16 May 2022; Accepted 20 May 2022

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