A fluorophore's electron-deficiency does matter in designing high-performance near-infrared fluorescent probes.
A fluorophore's electron-deficiency does matter in designing high-performance near-infrared fluorescent probes.
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荧光团的缺电子对于设计高性能近红外荧光探针确实很重要
DOI：
10.1039/d0sc04411c
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发表时间：
2020-09-21
期刊：
影响因子：
8.4
通讯作者：
Han KL
中科院分区：
文献类型：
--
作者：
Zhang XX;Qi H;Liu YL;Yang SQ;Li P;Qiao Y;Zhang PY;Wen SH;Piao HL;Han KL
现有的大多数谷胱甘肽S转移酶(GST)荧光探针，包括我们最近开发的基于1，8-萘二甲酰亚胺(NI)的Ni3，由于穿透性不足，其发射波长较短，限制了其应用。为了实现更深层次的成像，需要近红外(NIR)荧光探头。本文首次报道了利用近红外荧光载体HCy设计的GSTs近红外荧光探针，它相对于NiI具有更高的亮度、亲水性和电子缺陷性。有趣的是，对于相同的受体单元，无论受体单元的具体化学结构如何，基于HCy的探针总是比基于NI的探针对谷胱甘肽更具反应性。综合分析表明，这是由于HCY具有较高的电子缺陷，而不是其较高的亲水性所致。此外，由于自体荧光的笼化对于近红外探针来说是至关重要的，并且更难通过光诱导电子转移(PET)来实现，首次用飞秒瞬时吸收和理论计算证明了基于HCy的探针的猝灭机理是PET。因此，与Ni3中采用的受体单元相比，使用活性较低的受体单元的HCy2和HCy9被证明是最合适的近红外探针，具有高灵敏度和几乎没有非酶背景噪声。然后成功地应用于体内细胞、组织和肿瘤移植瘤中GST的检测。此外，与具有广泛同工酶选择性的HCy2不同，HCy9是GSTA1-1所特有的，这归因于其较低的反应活性和基于对接模拟的GSTA1-1通过氢键稳定活性中间体的较高效率。
The applications of most fluorescent probes available for Glutathione S-Transferases (GSTs), including NI3 which we developed recently based on 1,8-naphthalimide (NI), are limited by their short emission wavelengths due to insufficient penetration. To realize imaging at a deeper depth, near-infrared (NIR) fluorescent probes are required. Here we report for the first time the designing of NIR fluorescent probes for GSTs by employing the NIR fluorophore HCy which possesses a higher brightness, hydrophilicity and electron-deficiency relative to NI. Intriguingly, with the same receptor unit, the HCy-based probe is always more reactive towards glutathione than the NI-based one, regardless of the specific chemical structure of the receptor unit. This was proved to result from the higher electron-deficiency of HCy instead of its higher hydrophilicity based on a comprehensive analysis. Further, with caging of the autofluorescence being crucial and more difficult to achieve via photoinduced electron transfer (PET) for a NIR probe, the quenching mechanism of HCy-based probes was proved to be PET for the first time with femtosecond transient absorption and theoretical calculations. Thus, HCy2 and HCy9, which employ receptor units less reactive than the one adopted in NI3, turned out to be the most appropriate NIR probes with high-sensitivity and little nonenzymatic background noise. They were then successfully applied to detecting GST in cells, tissues and tumor xenografts in vivo. Additionally, unlike HCy2 with a broad isoenzyme selectivity, HCy9 is specific for GSTA1-1, which is attributed to its lower reactivity and the higher effectiveness of GSTA1-1 in stabilizing the active intermediate via H-bonds based on docking simulations.
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