Fluorescent chemosensors for ions and neutral analytes have been widely applied in many diverse fields such as biology, physiology, pharmacology, and environmental sciences. The field of fluorescent chemosensors has been in existence for about 150 years. In this time, a large range of fluorescent chemosensors have been established for the detection of biologically and/or environmentally important species. Despite the progress made in this field, several problems and challenges still exist. This tutorial review introduces the history and provides a general overview of the development in the research of fluorescent sensors, often referred to as chemosensors. This will be achieved by highlighting some pioneering and representative works from about 40 groups in the world that have made substantial contributions to this field. The basic principles involved in the design of chemosensors for specific analytes, problems and challenges in the field as well as possible future research directions are covered. The application of chemosensors in various established and emerging biotechnologies, is very bright.

Hypochlorous acid/hypochlorite (HOCl/ OCl − ), one of the most important reactive oxygen species (ROS), plays vital roles in various physiological and pathological processes. At normal concentrations, OCl − acts as part of an immune defense system by destroying invasive bacteria and pathogens. However, nonproperly located or excessive amounts of OCl − are related to many diseases, including cancers. Thus, detection of OCl − has great importance. Owing to their high sensitivities, selectivities, fast response times, technical simplicities, and high temporal and spatial resolution, fluorescent probes are powerful tools for in vitro and in vivo sensing of target substances. This Account focuses on the development of new chemosensors for detection of OCl − , which operate by undergoing a chemical reaction with this ROS in conjunction with a change in emission properties. As part of the presentation, we first introduce several important factors that need to be considered in the design of fluorescent chemosensors for OCl − , including fluorophores, reaction groups, cosolvents, and buffers. Discussion here revolves around the need to select fluorophores that resist oxidation by OCl − . As well, attention is given to the sensitivities and selectivities of groups in the sensors that react with OCl − to trigger a fluorescence response. Moreover, well-known reaction groups, which react with highly reactive ROS (hROS), have been redesigned to be specific for OCl − . In addition, it is pointed out that several cosolvents and buffers such as DMSO and HEPES are not suitable for use in systems for the detection of OCl − because they are readily oxidized by this ROS. We further discuss recent investigations carried out by us and others aimed at the development of fluorescent probes for in vitro and in vivo detection of OCl − . These efforts led to the new "dual lock" strategy for designing OCl − chemosensors as well as several new specific reaction groups such as imidazoline-2-thiones and imidazoline-2-boranes. Probes created using this strategy and the new reacting groups have been successfully applied to imaging exogenous and endogenous OCl − in live cells and/or tissues. The design concepts and strategies emanating from our studies of fluorescent OCl − probes have provided insight into the general field of fluorescent probes. Despite the progress made thus far, challenges still remain in developing and applying fluorescent OCl − probes. For example, more highly specific and sensitive fluorescent OCl − probes are still in great demand for studies of the biological roles played by OCl − . Thus, interdisciplinary collaborations of chemists, biologists, and medical practitioners are needed to drive future developments of OCl − probes for disease diagnosis and drug screening.

The extreme toxicity and ready accessibility of nerve agents and phosgene has caused an increase in the demand to develop effective systems for the detection of these substances. Among the traditional platforms utilized for this purpose, chemosensors including surface acoustic wave (SAW) sensors, enzymes, carbon nanotubes, nanoparticles, and chromophore based sensors have attracted increasing attention. In this review, we describe in a comprehensive manner recent progress that has been made on the development of chromophore-based chemosensors for detecting nerve agents (mimic) and phosgene. This review comprises two sections focusing on studies of the development of chemosensors for nerve agents (mimic) and phosgene. In each of the sections, the discussion follows a format which concentrates on different reaction sites/mechanisms involved in the sensing processes. Finally, chemosensors uncovered in these efforts are compared with those based on other sensing methods and challenges facing the design of more effective chemosensors for the detection of nerve agents (mimic) and phosgene are discussed.

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