β-氯丙烯醛与间氨基噻吩的生物正交反应制备同时双色成像近红外荧光探针，这一成果由广西师范大学化学与药学学院教授沈星灿研究团队经过不懈努力而取得。2025年2月11日出版的《美国化学会杂志》发表了这项成果。

在此，研究人员报道了一种新的荧光生物正交反应，涉及β-氯丙烯醛（β-CAs）和间氨基噻吩（m-AT₁），其荧光在原位产生荧光团后增加了500倍以上。β-CAs在生理条件下稳定，在生物亲核试剂存在下与m-AT₁发生快速反应（β-CA₉, k₂ = 2.2×10² M^-1 s^-1，在H₂O中）和化学选择性反应，即使在无溶剂条件下，反应也进行得很快。

此外，控制β-CAs的共轭长度可以使探针的发射波长从627nm微调到778nm。这些探针允许同时标记多个细胞器而无需洗涤步骤，并且在活体小鼠中实现双色肿瘤可视化。小组相信这项研究不仅为开发具有优越开启行为的近红外荧光探针提供了新的见解，而且还为生物医学研究提供了一种具有广泛应用潜力的荧光生物正交反应CA-AT。

据了解，基于高荧光探针的生物正交化学已成为一种很有前途的生物医学应用工具。然而，大多数荧光探针都是通过在经典荧光团中引入生物正交伴侣作为荧光猝灭剂来设计的，随着发射波长向近红外（NIR）区域移动，这些探针的荧光性会逐渐恶化，这极大地限制了它们在体内的应用。

附：英文原文

Title: Bioorthogonal Reaction of β-Chloroacroleins with meta-Aminothiophenol to Develop Near-Infrared Fluorogenic Probes for Simultaneous Two-color Imaging

Author: Liping Wang, Yujie Huang, Jing Wang, Yulan Jiang, Bang-Ping Jiang, Hua Chen, Hong Liang, Xing-Can Shen

Issue&Volume: February 11, 2025

Abstract: Highly fluorogenic probe based bioorthogonal chemistry has become a promising tool in biomedical applications. However, the majority of fluorogenic probes are designed by introducing a bioorthogonal partner as a fluorescence quencher into classical fluorophores, and these probes exhibit a deteriorating fluorogenicity as the emission wavelength shifts toward the near-infrared (NIR) region, greatly limiting their applications in vivo. Herein, we report a novel fluorogenic bioorthogonal reaction involving β-chloroacroleins (β-CAs) and meta-aminothiophenol (m-AT₁), whose fluorescence increases more than 500-fold upon in situ generating fluorophores. β-CAs are stable under physiological conditions and react rapidly (β-CA9, k2 = 2.2 ×10² M^–1 s^–1, in H₂O) and chemoselectively with m-AT₁ in the presence of biological nucleophiles, and delightfully, the reaction proceeds swiftly even under solvent-free conditions. Furthermore, manipulating the conjugate length of  β-CAs enables the emission wavelength of the probes to be fine-tuned from 627 to 778 nm. These probes allow the simultaneous labeling of multiple cellular organelles without washing steps, and two-color tumor visualization is achieved in living mice. We believe this study not only provides new insights for the development of NIR fluorogenic probes with superior turn-on behaviors but  also presents a promising fluorogenic bioorthogonal reaction CA-AT with widespread potential applications in biomedical research.

DOI: 10.1021/jacs.4c16074

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c16074