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<p>Lysosomal pH is important for regulating various physiological processes, such as cell signaling, energy metabolism, protein degradation, and plasma membrane repair. Therefore, it is important to develop fluorescent pH probe for the investigation of lysosome-related biological processes. Herein, we developed a highly selective turn-on fluorescent probe (<b>TCF-TME</b>) by introducing <i>N</i>,<i>N</i>-dimethylaminoethyl group as pH controller and lysosome-targeting unit. <b>TCF-TME</b> exhibited high selectivity, excellent photostability, and a fast response to pH changes. Density functional theory calculation confirmed that the protonation <i>N</i>,<i>N</i>-dimethylaminoethyl group inhibits the photoinduced electron transfer process from <i>N</i>,<i>N</i>-dimethylaminoethyl group to fluorophore. for monitoring lysosomal pH values. Also, the introduction of the <i>N</i>,<i> N</i>-dimethylamino group allows the probe to selectively accumulate in lysosomes with a high Pearson’s coefficient (0.92), and the suitable pKa value (7.57) enables the probe to visualize lysosomal pH changes triggered by chloroquine. Thus, <b>TCF-TME</b> is an excellent candidate for understanding the biological mechanisms.</p>

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A Highly Selective Fluorescent pH Probe in Red to NIR Region and its Application for the Monitoring Lysosomal pH Fluctuation in Living Cells

  • 期刊论文

  • 发表日期：

    2025年10月15日

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  • Xiaofei Yin,
  • Yibin Wang,
  • Boyang Zhang,
  • Ning Du,
  • Zongxing Wang,
  • Jianbu Wang

摘要

Lysosomal pH is important for regulating various physiological processes, such as cell signaling, energy metabolism, protein degradation, and plasma membrane repair. Therefore, it is important to develop fluorescent pH probe for the investigation of lysosome-related biological processes. Herein, we developed a highly selective turn-on fluorescent probe (TCF-TME) by introducing N,N-dimethylaminoethyl group as pH controller and lysosome-targeting unit. TCF-TME exhibited high selectivity, excellent photostability, and a fast response to pH changes. Density functional theory calculation confirmed that the protonation N,N-dimethylaminoethyl group inhibits the photoinduced electron transfer process from N,N-dimethylaminoethyl group to fluorophore. for monitoring lysosomal pH values. Also, the introduction of the N, N-dimethylamino group allows the probe to selectively accumulate in lysosomes with a high Pearson’s coefficient (0.92), and the suitable pKa value (7.57) enables the probe to visualize lysosomal pH changes triggered by chloroquine. Thus, TCF-TME is an excellent candidate for understanding the biological mechanisms.