Wilson Liam T, Tipping William J, Jamieson Lauren E, Wetherill Corinna, Henley Zoë, Faulds Karen, Graham Duncan, Mackay Simon P, Tomkinson Nicholas C O
Department of Pure and Applied Chemistry, WestCHEM, Thomas Graham Building, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, UK.
Analyst. 2020 Aug 7;145(15):5289-5298. doi: 10.1039/d0an00865f. Epub 2020 Jul 16.
Intracellular pH (pH) homeostasis is intertwined with a myriad of normal cellular behaviors as well as pathological processes. As such, small molecule probes for the measurement of pH are invaluable tools for chemical biology, facilitating the study of the role of pH in cellular function and disease. The field of small molecule pH sensors has traditionally been dominated with probes based on fluorescent scaffolds. In this study, a series of low molecular weight (<260) oligoyne compounds have been developed which exhibit pH sensitive alkyne stretching frequencies (ν) in Raman spectroscopy. The modular design of the compounds enabled tuneability of their pK(H) through simple structural modification, such that continuous pH sensitivity is achieved over the range 2-10. Alkyne stretching bands reside in the 'cell-silent' region of the Raman spectrum (1800-2600 cm) and are readily detectable in a cellular environment with subcellular spatial resolution. This enabled the application of a pH sensitive oligoyne compound to the ratiometric sensing of pH in prostate cancer (PC3) cells in response to drug treatment. We propose that probes based on Alkyne Tag Raman Imaging offer an entirely new platform for the sensing of pH, complementary to fluorescence microscopy.
细胞内pH值（pH）稳态与众多正常细胞行为以及病理过程相互交织。因此，用于测量pH值的小分子探针是化学生物学中非常有价值的工具，有助于研究pH值在细胞功能和疾病中的作用。传统上，小分子pH传感器领域一直由基于荧光支架的探针主导。在本研究中，已开发出一系列低分子量（<260）的寡炔化合物，它们在拉曼光谱中表现出对pH敏感的炔烃伸缩频率（ν）。这些化合物的模块化设计使其通过简单的结构修饰即可调节其pK(H)，从而在2至10的范围内实现连续的pH敏感性。炔烃伸缩带位于拉曼光谱的“细胞沉默”区域（1800 - 2600 cm），并且在具有亚细胞空间分辨率的细胞环境中易于检测。这使得一种对pH敏感的寡炔化合物能够应用于前列腺癌（PC3）细胞对药物治疗响应的pH值比率传感。我们认为基于炔烃标签拉曼成像的探针为pH传感提供了一个全新的平台，是荧光显微镜的补充。
