Green Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou, 450001, China.
School of Materials Science and Engineering, Zhengzhou University, Zhengzhou, 450001, China.
Anal Chim Acta. 2024 Nov 22;1330:343265. doi: 10.1016/j.aca.2024.343265. Epub 2024 Sep 19.
As an important reactive nitrogen species (RNS), HNO has been identified as an essential signaling molecule in many physiological processes. Ferroptosis produces a large amount of reactive oxygen species and reactive nitrogen species. However, the detailed mechanism of HNO during process of ferroptosis is rarely reported, especially in the near-infrared range. So, we designed a new near-infrared (NIR) HNO fluorescent probe X-1 based on a tricyanofuran (TCF) derivative and then applied it in ferroptosis imaging. The TCF derivative was chosen as the NIR fluorophore and 2-(diphenylphosphino)benzoate was used as the recognition group.
In this paper, a novel NIR HNO fluorescent probe X-1 based on tricyanofuran (TCF) derivatives was synthesized using the Staudinger linkage reaction. X-1 exhibited high selectivity for HNO in the near-infrared region (λ = 660 nm). When the recognition group undergoes the Staudinger linkage reaction with HNO, the NIR fluorescence emission increased significantly with the enhancement of the ICT effect. The response mechanism of X-1 to HNO was verified by high-resolution mass spectrometry (HRMS). Probe X-1 has the advantages of fast response (5 min), low detection limit, a large Stokes shift (120 nm) and strong anti-interference ability for HNO recognition. CCK-8 staining result indicates that the probe X-1 has good biocompatibility and little toxic effect on the cells. The probe was successfully applied to imaging the exogenous and endogenous HNO in living cells.
In the near-infrared range, HNO was discovered as a mediator of cellular signaling molecules, increasing in concentration during the process of ferroptosis. Furthermore, using this probe, it was further verified that sorafenib, a commonly used drug for cancer treatment, exerts its therapeutic effect by inducing ferroptosis in cancer cells, leading to cell death.
作为一种重要的活性氮物种（RNS），HNO 已被确定为许多生理过程中的重要信号分子。铁死亡会产生大量的活性氧和活性氮。然而，HNO 在铁死亡过程中的详细机制很少有报道，特别是在近红外范围内。因此，我们设计了一种基于三氰呋喃（TCF）衍生物的新型近红外（NIR）HNO 荧光探针 X-1，并将其应用于铁死亡成像。TCF 衍生物被选为近红外荧光团，2-（二苯基膦基）苯甲酸酯被用作识别基团。
在本文中，我们通过 Staudinger 连接反应合成了一种基于三氰呋喃（TCF）衍生物的新型近红外 HNO 荧光探针 X-1。X-1 在近红外区域（λ=660nm）对 HNO 具有高选择性。当识别基团与 HNO 发生 Staudinger 连接反应时，NIR 荧光发射强度显著增加，ICT 效应增强。通过高分辨率质谱（HRMS）验证了 X-1 对 HNO 的响应机制。探针 X-1 具有快速响应（5min）、检测限低、Stokes 位移大（120nm）和对 HNO 识别的强抗干扰能力等优点。CCK-8 染色结果表明，探针 X-1 具有良好的生物相容性，对细胞的毒性作用较小。该探针成功应用于活细胞中外源和内源性 HNO 的成像。
在近红外范围内，HNO 被发现是细胞信号分子的介体，在铁死亡过程中浓度增加。此外，使用该探针进一步证实，索拉非尼是一种常用于癌症治疗的药物，通过诱导癌细胞发生铁死亡从而导致细胞死亡来发挥其治疗作用。
