General Design Strategy to Precisely Control the Emission of Fluorophores via a Twisted Intramolecular Charge Transfer (TICT) Process
General Design Strategy to Precisely Control the Emission of Fluorophores via a Twisted Intramolecular Charge Transfer (TICT) Process
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DOI：
10.1021/jacs.2c06397
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发表时间：
2022-10-03
影响因子：
15
通讯作者：
Urano, Yasuteru
中科院分区：
文献类型：
--
作者：
Hanaoka, Kenjiro;Iwaki, Shimpei;Urano, Yasuteru
用于生物成像的荧光探针已成为生命科学和医学的重要工具，其发展的关键是精确理解可用于荧光关/开控制的机制，例如光诱导电子转移（PeT）和Fo 'rster共振能量转移（FRET）。在这里，我们建立了一个新的分子设计策略，合理地开发可激活的荧光探针，表现出响应于目标生物分子的荧光关闭/打开的变化，通过控制扭曲的分子内电荷转移（TICT）过程。该方法是在对N-苯基罗丹明染料（QSY系列）的荧光猝灭机理进行深入研究的基础上，通过含时密度泛函理论（TD-DFT）计算和对它们的衍生物进行物理化学评价而发展起来的。为了说明和验证这种基于TICT的设计策略，我们采用它来开发HaloTag和SNAP标签的实用荧光探针。我们进一步表明，TICT控制的荧光关/开机制是通过合成一个Si-罗丹明为基础的荧光探针HaloTag，从而提供了一个调色板的化学染料，跨越可见光和近红外范围的推广。
Fluorogenic probes for bioimaging have become essential tools for life science and medicine, and the key to their development is a precise understanding of the mechanisms available for fluorescence off/on control, such as photoinduced electron transfer (PeT) and Fo''rster resonance energy transfer (FRET). Here we establish a new molecular design strategy to rationally develop activatable fluorescent probes, which exhibit a fluorescence off/on change in response to target biomolecules, by controlling the twisted intramolecular charge transfer (TICT) process. This approach was developed on the basis of a thorough investigation of the fluorescence quenching mechanism of N-phenyl rhodamine dyes (commercially available as the QSY series) by means of time dependent density functional theory (TD-DFT) calculations and photophysical evaluation of their derivatives. To illustrate and validate this TICT-based design strategy, we employed it to develop practical fluorogenic probes for HaloTag and SNAP-tag. We further show that the TICT-controlled fluorescence off/on mechanism is generalizable by synthesizing a Si-rhodamine-based fluorogenic probe for HaloTag, thus providing a palette of chemical dyes that spans the visible and near-infrared range.