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Reaction-based small-molecule fluorescent probes for chemoselective bioimaging

Nature Chemistry volume 4, pages 973–984 (2012)Cite this article

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Abstract

The dynamic chemical diversity of elements, ions and molecules that form the basis of life offers both a challenge and an opportunity for study. Small-molecule fluorescent probes can make use of selective, bioorthogonal chemistries to report on specific analytes in cells and in more complex biological specimens. These probes offer powerful reagents to interrogate the physiology and pathology of reactive chemical species in their native environments with minimal perturbation to living systems. This Review presents a survey of tools and tactics for using such probes to detect biologically important chemical analytes. We highlight design criteria for effective chemical tools for use in biological applications as well as gaps for future exploration.

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Figure 1: Overview of organic and metal-mediated reaction-based strategies for the chemoselective bioimaging of small-molecule and metal ion analytes in biological systems.
Figure 2: Representative oxidative cycloaddition reactions for fluorescence bioimaging.
Figure 3: Representative oxidative cleavage reactions for small-molecule detection.
Figure 4: Representative reductive cleavage, nucleophilic reactions and tandem processes for detection of small molecules.
Figure 5: Representative metal-ligand substitution and metal-mediated redox addition/cleavage reactions for small-molecule detection.
Figure 6: Representative Lewis acid hydrolysis, organometallic and small-molecule activation reactions for specific metal ion detection.
Figure 7: Representative bioimaging applications with reaction-based small-molecule fluorescent probes for highly reactive species and metal ions.

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Acknowledgements

We thank the NIH (GM 79465), the Packard Foundation, Amgen, Astra Zeneca and Novartis for funding our laboratory's work on bioimaging. C.J.C. is an Investigator with the Howard Hughes Medical Institute. J.C. thanks the Human Frontiers Science Program for a postdoctoral fellowship and S.C.D. thanks Novartis for a graduate fellowship. We thank L. Lavis for sharing a figure template.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of California, Berkeley, 94720, California, USA

    Jefferson Chan, Sheel C. Dodani & Christopher J. Chang

  2. Department of Molecular and Cell Biology, University of California, Berkeley, 94720, California, USA

    Christopher J. Chang

  3. Howard Hughes Medical Institute, University of California, Berkeley, 94720, California, USA

    Christopher J. Chang

Authors
  1. Jefferson Chan
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  2. Sheel C. Dodani
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  3. Christopher J. Chang
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Correspondence to Christopher J. Chang.

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Chan, J., Dodani, S. & Chang, C. Reaction-based small-molecule fluorescent probes for chemoselective bioimaging. Nature Chem 4, 973–984 (2012). https://doi.org/10.1038/nchem.1500

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