Abstract
A novel pH-responsive probe based on an imidazo[1,2-a]indole fluorophore architecture is reported. The probe was highly selective to strongly acidic pH (pKa = 3.56) with high sensitivity and a fast response time (within 30 s). The probe did not demonstrate any fluorescence changes in the presence of interfering metal ions, and it featured excellent reversibility under strongly acidic conditions. The mechanism of detection of the probe was determined to be based on intramolecular charge transfer (ICT) at different pH. The probe was also able to be used for imaging for detecting acidic pH in Saccharomyces cerevisiae.
Data Availability
The authors declare that the data supporting the findings of this study are available in the article and the supplementary materials.
References
Yin J, Hu Y, Yoon J (2015) Fluorescent probes and bioimaging: alkali metals, alkaline earth metals and pH. Chem Soc Rev 44:4619–4644
Wan Q, Chen S, Shi W, Li L, Ma H (2014) Lysosomal pH rise during heat shock monitored by a lysosome-targeting near-infrared ratiometric fluorescent probe. Angew Chem Int Ed 53:10916–10920
Yuan L, Wang L, Agrawalla BK, Park SJ, Zhu H, Sivaraman B, Peng JJ, Xu QH, Chang YT (2015) Development of targetable two-photon fluorescent probes to image hypochlorous acid in mitochondria and lysosome in live cell and inflamed mouse model. J Am Chem Soc 137:5930–5938
Saha UC, Dhara K, Chattopadhyay B, Mandal SK, Mondal S, Sen S, Mukherjee M, van Smaalen S, Chattopadhyay P (2011) A new half-condensed Schiff base compound: highly selective and sensitive pH-responsive fluorescent sensor. Org Lett 13:4510–4513
Niu H, Zhang Y, Tang J, Zhu X, Ye Y, Zhao Y (2020) A bifunctional fluorescent sensor for CCCP-induced cancer cell apoptosis imaging. Chem Commun 56:12423–12426
Qu G, Zhang Y, Ma X (2019) Recent progress on pure organic room temperature phosphorescence materials based on host-guest interactions. Chin Chem Lett 30:1809–1814
Srivastava J, Barber DL, Jacobson MP (2007) Intracellular pH sensors: design principles and functional significance. Physiology 22:30–39
Li YZ, Wang XP (2014) Study on pH determination based on voltametric ion-selective electrode. China Meas Test 40:47–50
Yang Y, Zhao Q, Feng W, Li FY (2013) Luminescent chemodosimeters for bioimaging. Chem Rev 113:192–270
Ge YQ, Liu AK, Dong J, Duan GY, Cao XQ, Li FY (2017) A simple pH fluorescent probe based on new fluorophore indolizine for imaging of living cells. Sensors Actuators B 247:46–52
Ge YQ, Wei P, Wang T, Cao XQ, Zhang DS, Li FY (2018) A simple fluorescent probe for monitoring pH in cells based on new fluorophore pyridobenzimidazole. Sensors Actuators B 254:314–320
Zhang P, Lv HY, Duan GY, Dong J, Ge YQ (2018) A novel pyrazolo[1,5-a]pyridine fluorophore and its application to detect pH in cells. RSC Adv 8:30732–30735
Han J, Burgess K (2010) Fluorescent indicators for intracellular pH. Chem Rev 110:2709–2728
Fan L, Fu YJ, Liu QL, Lu DT, Dong C, Shuang SM (2012) Novel far-visible and near-infrared pH probes based on styrylcyanine for imaging intracellular pH in live cells. Chem Commun 48:11202–11204
Zhou XF, Su FY, Lu HG, Senechal-Willis P, Tian YQ, Johnson RH, Meldrum DR (2012) An FRET-based ratiometric chemosensor for in vitro cellular fluorescence analyses of pH. Biomaterials 33:171–180
Miao F, Song GF, Sun YM, Liu Y, Guo FQ, Zhang WJ, Tian MG, Yu XQ (2013) Fluorescent imaging of acidic compartments in living cells with a high selective novel one-photon ratiometric and two-photon acidic pH probe. Biosens Bioelectron 50:42–49
Krulwich TA, Sachs G, Padan E (2011) Molecular aspects of bacterial pH sensing and homeostasis. Nat Rev Microbiol 9:330–343
Dadashpour S, Emami S (2018) Indole in the target-based design of anticancer agents: A versatile scaffold with diverse mechanisms. Eur J Med Chem 150:9–29
de Sá Alves FR, Barreiro EJ, Fraga CA (2009) From nature to drug discovery: the indole scaffold as a ‘privileged structure’. Mini Rev Med Chem 9:782–793
Shang X, Chen C, Qiu H, Chen W (2014) Silver(I)-promoted intramolecular addition of N-heterocyclic carbenes towards unsaturated esters in water. Tetrahedron 70:3073–3077
Ren ZL, Cai S, Liu YY, Xie YQ, Yuan D, Lei M, He P, Wang L (2020) C(sp2)-H functionalization of imidazole at the C2- and C4-positionvia palladium-catalyzed isocyanide insertion leading to indeno[1,2-d]imidazole and imidazo[1,2-a]indole derivatives. J Org Chem 85:11014–11024
Kim HJ, Heo CH, Kim HM (2013) Benzimidazole-based ratiometric two-photon fluorescent probes for acidic pH in live cells and tissues. J Am Chem Soc 135:17969–17977
He LW, Lin WY, Xu QY, Ren MG, Wei HP, Wang JY (2015) A simple and effective capping approach to readily tune the fluorescence of near-infrared cyanines. Chem Sci 6:4530–4536
Dong BL, Song XZ, Wang C, Kong XQ, Tang YH, Lin WY (2016) Dual site-controlled and lysosome-targeted intramolecular charge transfer photoinduced electron transfer-fluorescence resonance energy transfer fluorescent probe for monitoring pH changes in living cells. Anal Chem 88:4085–4091
Forbes IT, Morgan HKA, Thompson M (1996) A synthesis of novel IH-imidazo [1,2-a]indole-3-carboxylates. Synth Commun 26:745–754
Funding
This work was supported by the Innovative Research Programs of Higher Education of Shandong Province (2019KJC009), the Science Foundation of Shandong Province for Excellent Young Scholars (ZR2017JL015), and the Natural Science Foundation of China (21,602,153).
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Yanhao Xu, and Ruikang Duan. Data analysis were performed by Hao Liu, and Chengcai Xia. The first draft of the manuscript was written by Guiyun Duan and Yanqing Ge. All authors read and approved the final manuscript.
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Xu, Y., Duan, R., Liu, H. et al. Preparation of a Novel pH-responsive Fluorescent Probe Based on an Imidazo[1,2-a]indole Fluorophore and its Application in Detecting Extremely Low pH in Saccharomyces cerevisiae. J Fluoresc 31, 1219–1225 (2021). https://doi.org/10.1007/s10895-021-02739-8
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DOI: https://doi.org/10.1007/s10895-021-02739-8