Small-molecule fluorophores and fluorescent probes for bioimaging

Fluorescent compounds based on synthetic small molecules are powerful tools to visualize biological events in living cells and organisms. Ever since the discovery of organic fluorescent compounds in the late nineteenth century, efforts have been made to see the behaviors of specific biomolecules in living systems by using these dyes as labels. Also, following the development of fluorescent Ca2+ indicators in the 1980s, many fluorescent probes or biosensors, which are defined as molecules that show a change in fluorescence properties in the presence of their target molecule, have been reported and applied in biological research. Today, a variety of probes are available that target metal ions, pH, enzyme activities, and signaling molecules. In this review, we first consider the history of organic fluorescent molecules and discuss their utility for labeling biomolecules and staining cells. Then, we review recent progress in small-molecule fluorescent probes for metal ions and reactive oxygen species, focusing on representative work in each category. Finally, we briefly discuss attempts to create novel kinds of probes, including hybrids of small molecules and genetically encoded proteins, with the potential to overcome some of the limitations of current probes.