| Benzimidazole-Piperazine-Coumarin/CB7 Supramolecular PET Fluorochrome for Detection of Carnosol by Stimuli-Responsive Dye Displacement and pKa Tuning Rukayat Shola Bojesomo1; Na'il Saleh2; 1UNITED ARAB EMIRATE UNIVERSITY, Abu Dhabi, United Arab Emirates; 2UNITED ARAB EMIRATES UNIVERSITY, Al-Ain, United Arab Emirates; PAPER: 162/SolutionChemistry/Regular (Oral) SCHEDULED: 15:55/Wed. 30 Nov. 2022/Game ABSTRACT: In recent years, the number of indicator displacement assays (IDAs) [1] has increased as an eminent strategy for changing a synthetic receptor (host) into an optical sensor. In a conventional IDA, an indicator (dye) is first permitted to reversibly bind a host, before being dislodged from the host by a competitive analyte (drug) and thus the strategy regulates an optical signal despite the analyte and the host are both spectroscopically inactive. It is quite crucial that the indicator and analyte have similar affinity for the receptor.[2–6] A new fluorescent dye (4PBZC) comprises of coumarin, piperazine and benzimidazole (BZ) was designed, prepared and complexed to cucurbit[7]uril (CB7) to detect carnosol (CAR) anticancer drug in sub-nanomolar concentrations utilizing the supramolecular indicator displacement assay (IDA) strategy, the CB7-assisted pKa shift and the CB7-retarded photoinduced electron transfer (PET) process. The 2:1 host−guest complexation was confirmed by UV−visible absorption, fluorescence and proton NMR spectroscopy, which confirm binding to 4PBZC via the BZ and coumarin moieties. Also, CB7 preferentially binds the indicator dye via the protonated BZ group compared to the neutral BZ group, demonstrated by a high 2:1 binding constant (e.g., K = 5.5 × 106 M−1) of the complex in its protonated form, which led to an increase in the pKa of the BZ moiety by ca. 3.0 units after the addition of CB7. In the aqueous solution under pH of 6, switching the emission signals between 4PBZH+C/CB7 (ON state) and CAR/CB7NPs (OFF state) was achieved by displacement of the protonated dye from the cavity of CB7 by the CAR analyte. An efficient sensor was fabricated for the highly sensitive detection of CAR in aqueous solution at pH 6 with a low-detection limit (LOD) of 0.06 ng/mL (0.2 nM). References: (1) Nguyen, B. T.; Anslyn, E. V. Indicator–Displacement Assays. Coordination Chemistry Reviews 2006, 250 (23), 3118–3127. https://doi.org/10.1016/j.ccr.2006.04.009. (2) Sinn, S.; Biedermann, F. Chemical Sensors Based on Cucurbit[n]Uril Macrocycles. Israel Journal of Chemistry 2018, 58 (3–4), 357–412. https://doi.org/10.1002/ijch.201700118. (3) Ghale, G.; Nau, W. M. Dynamically Analyte-Responsive Macrocyclic Host–Fluorophore Systems. Acc. Chem. Res. 2014, 47 (7), 2150–2159. https://doi.org/10.1021/ar500116d. (4) Mako, T. L.; Racicot, J. M.; Levine, M. Supramolecular Luminescent Sensors. Chem. Rev. 2019, 119 (1), 322–477. https://doi.org/10.1021/acs.chemrev.8b00260. (5) Sinn, S.; Krämer, J.; Biedermann, F. Teaching Old Indicators Even More Tricks: Binding Affinity Measurements with the Guest-Displacement Assay (GDA). Chem. Commun. 2020, 56 (49), 6620–6623. https://doi.org/10.1039/D0CC01841D. (6) Sinn, S.; Spuling, E.; Bräse, S.; Biedermann, F. Rational Design and Implementation of a Cucurbit[8]Uril-Based Indicator-Displacement Assay for Application in Blood Serum. Chemical Science 2019, 10 (27), 6584–6593. https://doi.org/10.1039/C9SC00705A. |
