Contents lists available at ScienceDirect Sensors and Actuators B: Chemical journal homepage: www.elsevier.com/locate/snb Dioxetane-based chemiluminescent probe for fluoride ion-sensing in aqueous solution and living imaging Bowen Gu, Chao Dong, Ruwei Shen, Jian Qiang, Tingwen Wei, Fang Wang, Sheng Lu ⁎ , Xiaoqiang Chen ⁎ State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, Nanjing 211816, China ARTICLE INFO Keywords: Chemiluminescent probe Fluoride ion 1,2-Dioxetane Toothpaste Living mice In vivo imaging ABSTRACT Fluoride plays an important role in our daily life as it associates with a variety of biological and pathological processes. Hence, an analytic method that can detect fluoride ions under physiological conditions with high sensitivity and specificity, and fast response, is needed. Herein, we introduced a dioxetane-based chemilumi- nescent probe, CL-F, specifically designed for the detection of fluoride ions in physiological environment. The probe CL-F emitted strong green chemiluminescent light within 1 min when incubating with fluoride ions specifically. The linear range for sensing fluoride ions and limit of detection were determined to be 0–30 μM and 0.91 μM, respectively. The probe CL-F was then successfully applied in quantifying fluoride ions in toothpaste and in vivo imaging in living mice, demonstrating CL-F as a promising tool for sensing fluoride ion in vitro and in vivo. 1. Introduction Owing to the advances in molecular sensing approaches, the de- velopment of sensors with high sensitivity and selectivity for anions has attracted much attention due to their vital roles in chemical and bio- logical processes [1–6]. Fluoride is one of the anions that are most re- levant to our daily life. It is added as supplements in our daily goods, such as drinking water, milk, toothpaste and mouth rinses, due to its function in preventing tooth decay and osteoporosis [7,8]. However, excessive fluoride intake also leads to fluorosis, urolithiasis, or even cancer [9,10]. According to the U.S. Public Health Service, the optimal level of fluoride consumption is 1 mg per day, while the World Health Organization (WHO) recommends fluoride levels below 1.5 ppm in drinking water [11]. Since artificial sources of fluoride are also used in large-scale industrial applications, the produced industrial wastes would result in fluoride contamination in water sources, affecting our fluoride intake. Therefore, efficient and reliable sensing methods for fluoride levels in aqueous environment are highly demanded. The analytic approaches used for fluoride ion detection involve standard willard and winter methods, ion-selective electrode, and ion chromatography [12,13]. These conventional analytic methods have intrinsic drawbacks, such as complicated procedures, high cost and low mobility, which hinder the rapidness and convenience of fluoride de- tection. Recently, fluorescent chemosensors have received considerable attention due to their high sensitivity and specificity, and ease of op- erating, providing an alternative tool for the detection of fluoride ions [14–17]. But the inherent drawbacks of fluorescence assays, including photobleaching, phototoxicity and interference of autofluorescence from other species in the samples, restrict their practical applications. Comparing to fluorescence-based mechanisms, bio- and chemilu- minescent assays can generate optical signals without excitation from external light sources, rendering them higher reliability, sensitivity and signal-to-noise ratios [18]. Therefore, bio- and chemiluminescent probes have been widely used for in vitro and in vivo imaging of various enzymes and analytes [19–22]. To date, extensive examples of bio- and chemiluminescent probes are designed based on two major mechan- isms, firefly luciferase-luciferin system and adamantylidene - dioxe- tane model [23–28]. Despite holding advantages of sensitivity and high signal-to-noise ratio, firefly luciferase-luciferin systems require exo- genous gene expression of luciferase to trigger the luminescence, ele- vating the complexity in practical applications [29]. The adamantyli- dene - dioxetane developed by Schaap is a classic molecular model to construct chemiluminenscent probes, which do not require the activa- tion by oxidation due to the relative stable dioxetane moiety [30–32]. This system exhibits a good capability of emitting light in organic sol- vents with medium polarity, but performs badly under aqueous con- ditions [33]. The addition of a surfactant, enhancer Emerald-II, was found to amplify the luminescence in aqueous solution by providing a https://doi.org/10.1016/j.snb.2019.127111 Received 23 July 2019; Received in revised form 5 September 2019; Accepted 6 September 2019 ⁎ Corresponding authors. E-mail addresses: 88603328@qq.com (S. Lu), chenxq@njtech.edu.cn, chenxq@njut.edu.cn (X. Chen). Sensors & Actuators: B. Chemical 301 (2019) 127111 Available online 09 September 2019 0925-4005/ © 2019 Elsevier B.V. All rights reserved. T