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Fluorescent sensing of nucleic acids is a highly sensitive and efficient bioanalytical method for their study in cellular processes, detection and diagnosis in related diseases. However, the design of small molecule fluorescent probes for the selective binding and detection of RNA of a specific sequence is very challenging because of their diverse, dynamic, and flexible structures. By modifying a bis(amidinium)-based small molecular binder that is known to selectively target RNA with CAG repeats using an environment-sensitive fluorophore, a turn-on fluorescent probe featuring aggregation-induced emission (AIE) is successfully developed in this proof-of-concept study. The probe ( DB-TPE ) exhibits a strong, 19-fold fluorescence enhancement upon binding to a short CAG RNA, and the binding and fluorescence response was found to be specific to the overall RNA secondary structure with A·A mismatches. These promising analytical performances suggest that the probe could be applied in pathological studies, disease progression monitoring, as well as diagnosis of related neurodegenerative diseases due to expanded CAG RNA repeats.

Fluorescein-derived superoxide probes featuring a copper(II) complex that can be activated by superoxide to initiate ether bond cleavage and uncage a fluorescein reporter for imaging in live cells are described. Compared to other superoxide sensing moieties, this bond cleavage strategy can be modularly adapted to fluorescent reporters with different properties without compromising the superoxide reactivity and selectivity. A green-emitting probe and its lysosome-targeting analogue have been successfully developed. Both probes are sensitive with more than 30-fold fluorescence enhancement towards superoxide and are highly selective with no significant response towards other reactive oxygen species. A structure-activity relationship study of the copper-based superoxide trigger showed that the secondary coordination environment of the copper(II) center is important for the superoxide reactivity and selectivity. The probes have been applied in imaging changes in intracellular superoxide level in live HeLa and HEK293T cells upon menadione stimulation and also in a cellular inflammation model in RAW 264.7 cells., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Copper chemistry has been capitalized on in a wide spectrum of biological events. The central importance of copper in biology lies in the diverse chemical reactivity of the redox-active transition metal ranging from electron transfer, small molecule binding and activation, to catalysis. In addition to its many different roles in natural biological systems, the diverse chemical reactivity of copper also represents a rich opportunity and resource to develop synthetic bioanalytical tools for the study of biologically important species and molecules. In this mini-review, fluorescent probes featuring a specific copper-based chemical reaction to selectively detect a biologically relevant analyte will be discussed. In particular, fluorescent probes for sensing labile copper ions, amino acids and small reactive species will be highlighted. The chemical principles, advantages and limitations of the different types of copper-mediated chemical reactions in these fluorescent probes will be emphasized., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Iron is an essential metal for living organisms, but misregulation of its homeostasis at the cellular level can trigger detrimental oxidative and/or nitrosative stress and damage events. Motivated to help study the physiological and pathological consequences of biological iron regulation, we now report a reaction-based strategy for monitoring labile Fe(2+) pools in aqueous solution and living cells. Iron Probe 1 (IP1) exploits a bioinspired, iron-mediated oxidative C-O bond cleavage reaction to achieve a selective turn-on response to Fe(2+) over a range of cellular metal ions in their bioavailable forms. We show that this first-generation chemical tool for fluorescence Fe(2+) detection can visualize changes in exchangeable iron stores in living cells upon iron supplementation or depletion, including labile iron pools at endogenous, basal levels. Moreover, IP1 can be used to identify reversible expansion of labile iron pools by stimulation with vitamin C or the iron regulatory hormone hepcidin, providing a starting point for further investigations of iron signaling and stress events in living systems as well as future probe development.

A reaction-based strategy exploiting cobalt-mediated oxidative C-O bond cleavage affords a selective turn-on fluorescent probe for paramagnetic Co(2+) in water and in living cells., (This journal is © The Royal Society of Chemistry 2012)