Reactive oxygen (ROS) and nitrogen (RNS) species cause oxidative and nitrosative stresses, respectively. These stresses are implicated not only in diverse physiological processes but also in various pathological processes, including cancer and neurodegenerative disorders. In addition, some ROS and RNS in the environment are pollutants that threaten human health. As a consequence of these effects, sensitive methods, which can be employed to selectively monitor ROS and RNS in live cells, tissues and organisms as well as in environmental samples, are needed so that their biological roles can be understood and their concentrations in environmental samples can be determined. In this review, fluorescent, luminescent and colorimetric ROS and RNS probes, which have been developed since 2011, are comprehensively discussed.

Recent progress in the development of fluorescent, luminescent and colorimetric probes for detection of reactive oxygen and nitrogen species

Coumarins are a very large family of compounds containing the unique 2H-chromen-2-one motif, as it is known according to IUPAC nomenclature. Coumarin derivatives are widely found in nature, especially in plants and are constituents of several essential oils. Up to now, thousands of coumarin derivatives have been isolated from nature or produced by chemists. More recently, the coumarin platform has been widely adopted in the design of small-molecule fluorescent chemosensors because of its excellent biocompatibility, strong and stable fluorescence emission, and good structural flexibility. This scaffold has found wide applications in the development of fluorescent chemosensors in the fields of molecular recognition, molecular imaging, bioorganic chemistry, analytical chemistry, materials chemistry, as well as in the biology and medical science communities. This review focuses on the important progress of coumarin-based small-molecule fluorescent chemosensors during the period of 2012-2018. This comprehensive and critical review may facilitate the development of more powerful fluorescent chemosensors for broad and exciting applications in the future.

Coumarin-Based Small-Molecule Fluorescent Chemosensors.

The hypothesis is presented that changes in metal ion homeostatic control, particularly of redox-active metals such as iron and copper, in specific brain regions, leads to the generation of reactive oxygen species, which either directly damage key proteins, or lead to the formation of reactive aldehydes. These, in turn, generate protein carbonyls, leading to protein denaturation, aggregation, and a failure of the ubiquitin/proteasome system to eliminate these defective proteins. We present the evidence for metal based neurodegeneration in Parkinson's and Alzheimer's disease. Possible therapeutic strategies are presented which could remove such excesses of these specific metals and lead to the diminishment of the neurodegenerative processes. (C) 2007 Elsevier B.V. All rights reserved.

Metal based neurodegenerative diseases : From molecular mechanisms to therapeutic strategies

A new ratiometric fluorescent H2 O2 probe, benzopyrylium-coumarin (BC), is designed by using an oxonium moiety as the unique H2 O2 response site. The BC probe exhibits an extremely large emission shift of 221 nm in response to H2 O2 , and is successfully applied for the simultaneous near-infrared and two-photon imaging of H2 O2 in living cells, mouse-liver tissues, and zebrafish.

Simultaneous Near-Infrared and Two-Photon In Vivo Imaging of H2 O2 Using a Ratiometric Fluorescent Probe based on the Unique Oxidative Rearrangement of Oxonium.

Oxidative stress in neurodegeneration: cause or consequence?

A coumarin-based two-photon probe for hydrogen peroxide.

A new turn-on fluorescence probe based on rhodamine 6G for Hg 2+ was synthesized and characterized by NMR, IR and ESI–MS The probe L shows high selectivity and good sensitivity for Hg 2+ , which exhibited an obvious fluorescence change from colorless to pink in the presence of Hg 2+  The detection limit was estimated to be 13 × 10 −9  M and the Job’s plot investigation suggested that L was bound to Hg 2+ with a simple 1:2 stoichiometry in EtOH/H 2 O (1:1, v/v) solution Furthermore, biological experiments demonstrated that probe L has excellent membrane permeability and low cytotoxicity, which could be applied to monitor Hg 2+ in living cells, animal tissues and plant tissues

A selective turn-on fluorescent sensor for Hg (II) in living cells and tissues

The level of peroxynitrite (ONOO-) is closely related to the pathogenesis of a series of diseases. Hence, the accurate sensing of ONOO- is very important for a better understanding of its biological functions. Here, a time-resolved ratiometric nanoprobe (TD-DC) composed of an energy donor unit (Tb(DPA)3, where DPA signifies a dipicolinate dianion ligand) and an energy receptor unit (DC) was designed. The response of TD-DC toward ONOO- in vitro was assessed by luminescence intensity and lifetime. The results demonstrated that TD-DC could precisely (39 nM) detect ONOO- with high selectivity and efficiency (29 s). TD-DC was further successfully employed in sensing endogenous ONOO- in A-375 cells. Moreover, it could specifically localize in the mitochondrion, where endogenous ONOO- is mainly generated. The above results revealed that TD-DC is efficient and useful for real-time detection of ONOO- at subcellular levels.

Mito-Specific Ratiometric Terbium(III)-Complex-Based Luminescent Probe for Accurate Detection of Endogenous Peroxynitrite by Time-Resolved Luminescence Assay.

Small molecular biothiols (Cys, Hcy, and GSH) are intimately related to complicated metabolic process. On account of the analogous chemical construction and reactivity, it is still a challenging problem to diacritically detect biothiols, which seriously hinders people's understanding of their metabolic relationship and the reasons for biothiols-related illnesses. Therefore, a hydro-soluble NIR fluorescent probe (YF) with multiple sites and multiple excitations was designed for distinguishing biothiols. Across different excitation, YF displayed unique fluorescence signals: λex = 418 nm, λem = ∼496 nm; λex = 517 nm, λem = ∼576/733/783 nm; λex = 558 nm, λem = ∼611/733 nm, respectively. As far as we know, the different reaction mechanism that leading to different spectroscopic behaviors of YF towards biothiols were confirmed by DFT calculation for the first time. Significantly, YF was successfully applied to recognize Cys/Hcy, and GSH in A375 cells from different emission channels, and was determination of biothiols in fetal bovine serum samples and the result was in good agreement with that tested by Ellman method.

Hydro-soluble NIR fluorescent probe with multiple sites and multiple excitations for distinguishing visualization of endogenous Cys/Hcy, and GSH

A reversible fluorescent probe L based on rhodamine 6G is synthesized for the optical detection of Fe3+ in water. This probe displays favorable selectivity for Fe3+ with a 1 : 1 stoichiometry. It displays a fluorescence turn-on response in the process of rhodamine ring opening with Fe3+ and a fluorescence turn-off response with the addition of Na4P2O7 to the L-Fe3+ complex. The association constant between the probe and Fe3+ was detected to be 3.5 × 104 M−1, and the corresponding detection limit was calculated to be 1.9 × 10−8 M according to fluorescence titration analysis. Furthermore, bioimaging investigations indicated that this probe was cell permeable and suitable for monitoring intracellular Fe3+ in living cells by confocal microscopy.

Rong Shen

Papers

A coumarin-based two-photon probe for hydrogen peroxide.

A selective turn-on fluorescent sensor for Hg (II) in living cells and tissues

Mito-Specific Ratiometric Terbium(III)-Complex-Based Luminescent Probe for Accurate Detection of Endogenous Peroxynitrite by Time-Resolved Luminescence Assay.

Hydro-soluble NIR fluorescent probe with multiple sites and multiple excitations for distinguishing visualization of endogenous Cys/Hcy, and GSH

A reversible rhodamine 6G-based fluorescence turn-on probe for Fe3+ in water and its application in living cell imaging