Binding- and activity-based small molecule fluorescent probes for the detection of Cu+, Cu2+, Fe2+ and Fe3+ in biological systems

Although transition metals make up less than 0.1 % of the total mass in a human body, they have significant impacts on fundamental biological processes. Among them, copper(I) (Cu⁺), copper(II) (Cu²⁺), ferrous ion (Fe²⁺) and ferric ion (Fe³⁺) exhibited many vital biochemical events. Therefore, precisely monitoring their biological distribution and concentrations via modern analytical techniques are urgently required. In particular, small molecule fluorescent probes have enabled the real-time and in suit detection of the dynamic fluctuations and spatiotemporal distribution of these transition metal ions. In this work, abundant representative binding- and activity-based small molecule fluorescent probes for monitoring of Cu⁺, Cu²⁺, Fe²⁺ and Fe³⁺ from 2020 to 2024 are showcased. Moreover, the molecular design strategies, monitoring mechanisms, and biological applications of these fluorescence probes are described in detail. Furthermore, the strengths and weaknesses of various types of metal ion-responsive molecular probes are analyzed and discussed. In this regard, our underlying goal is to encourage the development of innovative small molecule fluorescent probes for detecting transition metal ions.