Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Synthetic fluorescent sensors for studying the cell biology of metals

A Corrigendum to this article was published on 01 August 2008

This article has been updated

Abstract

Metals are essential for sustaining all forms of life, but alterations in their cellular homeostasis are connected to severe human disorders, including cancer, diabetes and neurodegenerative diseases. Fluorescent small molecules that respond to metal ions in the cell with appropriate selectivity and sensitivity offer the ability to probe physiological and pathological consequences of the cell biology of metals with spatial and temporal fidelity. Molecular imaging of normal and abnormal cellular metal ion pools using these new chemical tools provides a host of emerging opportunities for visualizing, in real time, aspects of metal accumulation, trafficking, and function or toxicity in living systems. This review presents a brief survey of available synthetic small-molecule sensor types for fluorescence detection of cellular metals.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: A generalized model of cellular metal ion homeostasis.

Rebecca Henretta

Figure 2
Figure 3
Figure 4: Live-cell imaging with small-molecule fluorescent probes for metal ions.
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

Change history

  • 26 June 2008

    In the version of this article initially published, the chemical structures for S3 and RS2 in Figure 6 were incorrect. The error has been corrected in the HTML and PDF versions of the article.

References

  1. Lippard, S.J. & Berg, J.M. Principles of Bioinorganic Chemistry 139–175 (University Science Books, Mill Valley, California, USA, 1994).

    Google Scholar 

  2. Denk, W., Strickler, J.H. & Webb, W.W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990).

    Article  CAS  PubMed  Google Scholar 

  3. Lichtman, J.W. & Conchello, J.-A. Fluorescence microscopy. Nat. Methods 2, 910–919 (2005).

    CAS  PubMed  Google Scholar 

  4. Griffin, B.A., Adams, S.R. & Tsien, R.Y. Specific covalent labeling of recombinant protein molecules inside live cells. Science 281, 269–272 (1998).

    CAS  Google Scholar 

  5. Chang, M.C.Y., Pralle, A., Isacoff, E.Y. & Chang, C.J. A selective, cell-permeable optical probe for hydrogen peroxide in living cells. J. Am. Chem. Soc. 126, 15392–15393 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Gabe, Y., Urano, Y., Kikuchi, K., Kojima, H. & Nagano, T. Highly sensitive fluorescence probes for nitric oxide based on boron dipyrromethene chromophore-rational design of potentially useful bioimaging fluorescence probe. J. Am. Chem. Soc. 126, 3357–3367 (2004).

    CAS  PubMed  Google Scholar 

  7. Lim, M.H., Xu, D. & Lippard, S.J. Visualization of nitric oxide in living cells by a copper-based fluorescent probe. Nat. Chem. Biol. 2, 375–380 (2006).

    CAS  PubMed  Google Scholar 

  8. Miller, E.W., Tulyathan, O., Isacoff, E.Y. & Chang, C.J. Molecular imaging of hydrogen peroxide produced for cell signaling. Nat. Chem. Biol. 3, 263–267 (2007).

    CAS  PubMed  Google Scholar 

  9. Haugland, R.P. Handbook of Fluorescent Probes and Research Products 555–767 (Molecular Probes, Inc., Eugene, Oregon, USA, 2002).

    Google Scholar 

  10. Rosania, G.R., Lee, J.W., Ding, L., Yoon, H.S. & Chang, Y.T. Combinatorial approach to organelle-targeted fluorescent library on the styryl scaffold. J. Am. Chem. Soc. 125, 1130–1131 (2003).

    CAS  PubMed  Google Scholar 

  11. Tour, O. et al. Calcium Green FlAsH as a genetically targeted small-molecule calcium indicator. Nat. Chem. Biol. 3, 423–431 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Frederickson, C.J. Neurobiology of zinc and zinc-containing neurons. Int. Rev. Neurobiol. 31, 145–238 (1989).

    CAS  PubMed  Google Scholar 

  13. Li, Y., Hough, C.J., Frederickson, C.J. & Sarvey, J.M. Induction of mossy fiber -> CA3 long-term potentiation requires translocation of synaptically released Zn(II). J. Neurosci. 21, 8015–8025 (2001).

    CAS  PubMed  Google Scholar 

  14. Sensi, S.L., Yin, H.Z. & Weiss, J.H. AMPA/kainate receptor-triggered Zn(II) entry into cortical neurons induces mitochondrial Zn(II) uptake and persistent mitochondrial dysfunction. Eur. J. Neurosci. 12, 3813–3818 (2000).

    CAS  PubMed  Google Scholar 

  15. Chang, C.J. & Lippard, S.J. in Metal Ions in Life Sciences vol. 1, 321–370 (John Wiley & Sons, Ltd., West Sussex, UK, 2006).

    Google Scholar 

  16. Thompson, R.B. Studying zinc biology with fluorescence: ain't we got fun? Curr. Opin. Chem. Biol. 9, 526–532 (2005).

    CAS  PubMed  Google Scholar 

  17. Frederickson, C.J., Koh, J.-Y. & Bush, A.I. The neurobiology of zinc in health and disease. Nat. Rev. Neurosci. 6, 449–462 (2005).

    CAS  PubMed  Google Scholar 

  18. Kikuchi, K., Komatsu, K. & Nagano, T. Zinc sensing for cellular application. Curr. Opin. Chem. Biol. 8, 182–191 (2004).

    CAS  PubMed  Google Scholar 

  19. Minta, A., Kao, J.P. & Tsien, R.Y. Fluorescent indicators for cytosolic calcium based on rhodamine and fluorescein chromophores. J. Biol. Chem. 264, 8171–8178 (1989).

    CAS  PubMed  Google Scholar 

  20. Gee, K.R., Zhou, Z.L., Qian, W.J. & Kennedy, R. Detection and imaging of zinc secretion from pancreatic cells using a new fluorescent zinc indicator. J. Am. Chem. Soc. 124, 776–778 (2002).

    CAS  PubMed  Google Scholar 

  21. Lin, W., Mohandas, B., Fontaine, C. & Colvin, R. Release of intracellular Zn(II) in cultured neurons after brief exposure to low concentrations of exogenous nitric oxide. Biometals 20, 891–901 (2007).

    CAS  PubMed  Google Scholar 

  22. Sensi, S.L., Ton-That, D., Weiss, J.H., Rothe, A. & Gee, K.R. A new mitochondrial fluorescent zinc sensor. Cell Calcium 34, 281–284 (2003).

    CAS  PubMed  Google Scholar 

  23. Valentine, R.A. et al. ZnT5 variant B is a bidirectional zinc transporter and mediates zinc uptake in human intestinal Caco-2 cells. J. Biol. Chem. 282, 14389–14393 (2007).

    CAS  PubMed  Google Scholar 

  24. Walkup, G.K., Burdette, S.C., Lippard, S.J. & Tsien, R.Y. A new cell-permeable fluorescent probe for Zn(II). J. Am. Chem. Soc. 122, 5644–5645 (2000).

    CAS  Google Scholar 

  25. Burdette, S.C., Walkup, G.K., Spingler, B., Tsien, R.Y. & Lippard, S.J. Fluorescent sensors for Zn(II) based on a fluorescein platform: synthesis, properties and intracellular distribution. J. Am. Chem. Soc. 123, 7831–7841 (2001).

    CAS  PubMed  Google Scholar 

  26. Burdette, S.C., Frederickson, C.J., Bu, W.M. & Lippard, S.J. ZP4, an improved neuronal Zn(II) sensor of the Zinpyr family. J. Am. Chem. Soc. 125, 1778–1787 (2003).

    CAS  PubMed  Google Scholar 

  27. Chang, C.J. et al. Bright fluorescent chemosensor platforms for imaging endogenous pools if neuronal zinc. Chem. Biol. 11, 203–210 (2004).

    CAS  PubMed  Google Scholar 

  28. Chang, C.J. et al. ZP8, a neuronal zinc sensor with improved dynamic range; imaging zinc in hippocampal slices with two-photon microscopy. Inorg. Chem. 43, 6774–6779 (2004).

    CAS  PubMed  Google Scholar 

  29. Goldsmith, C.R. & Lippard, S.J. 6-methylpyridyl for pyridyl substitution tunes the properties of fluorescent zinc sensors of the zinpyr family. Inorg. Chem. 45, 555–561 (2006).

    CAS  PubMed  Google Scholar 

  30. Woodroofe, C.C., Masalha, R., Barnes, K.R., Frederickson, C.J. & Lippard, S.J. Membrane-permeable and -impermeable sensors of the Zinpyr family and their application to imaging of hippocampal zinc in vivo. Chem. Biol. 11, 1659–1666 (2004).

    CAS  PubMed  Google Scholar 

  31. Nolan, E.M., Burdette, S.C., Harvey, J.H., Hilderbrand, S.A. & Lippard, S.J. Synthesis and characterization of zinc sensors based on a monosubstituted fluorescein platform. Inorg. Chem. 43, 2624–2635 (2004).

    CAS  PubMed  Google Scholar 

  32. Nolan, E.M., Jaworski, J., Racine, M.E., Sheng, M. & Lippard, S.J. Midrange affinity fluorescent Zn(II) sensors of the Zinpyr family: syntheses, characterization, and biological imaging applications. Inorg. Chem. 45, 9748–9757 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Nolan, E.M. et al. Zinspy sensors with enhanced dynamic range for imaging neuronal cell zinc uptake and mobilization. J. Am. Chem. Soc. 128, 15517–15528 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Nolan, E.M. et al. QZ1 and QZ2: rapid, reversible quinoline-derivatized fluoresceins for sensing biological Zn(II). J. Am. Chem. Soc. 127, 16812–16823 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Sinclair, S.A., Sherson, S.M., Jarvis, R., Camakaris, J. & Cobbett, C.S. The use of the zinc-fluorophore, Zinpyr-1, in the study of zinc homeostasis in Arabidopsis roots. New Phytol. 174, 39–45 (2007).

    CAS  PubMed  Google Scholar 

  36. Giblin, L.J. et al. Zinc-secreting Paneth cells studied by ZP fluorescence. J. Histochem. Cytochem. 54, 311–316 (2006).

    CAS  PubMed  Google Scholar 

  37. Hirano, T., Kikuchi, K., Urano, Y., Higuchi, T. & Nagano, T. Highly zinc-selective fluorescent sensor molecules suitable for biological applications. J. Am. Chem. Soc. 122, 12399–12400 (2000).

    CAS  Google Scholar 

  38. Takeda, A. et al. Zinc release from Schaffer collaterals and its significance. Brain Res. Bull. 68, 442–447 (2006).

    CAS  PubMed  Google Scholar 

  39. Takeda, A., Fuke, S., Minami, A. & Oku, N. Role of zinc influx via AMPA/kainate receptor activation in metabotropic glutamate receptor-mediated calcium release. J. Neurosci. Res. 85, 1310–1317 (2007).

    CAS  PubMed  Google Scholar 

  40. Ueno, S. et al. Mossy fiber Zn(II) spillover modulates heterosynaptic N-methyl-D-aspartate receptor activity in hippocampal CA3 circuits. J. Cell Biol. 158, 215–220 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Hirano, T., Kikuchi, K., Urano, Y. & Nagano, T. Improvement and biological applications of fluorescent probes for zinc, ZnAFs. J. Am. Chem. Soc. 124, 6555–6562 (2002).

    CAS  PubMed  Google Scholar 

  42. Colvin, R.A. et al. Evidence for pH dependent Zn(II) influx in K562 erythroleukemia cells: studies using ZnAF-2F fluorescence and Zn-65(II) uptake. Arch. Biochem. Biophys. 442, 222–228 (2005).

    CAS  PubMed  Google Scholar 

  43. Komatsu, K., Kikuchi, K., Kojima, H., Urano, Y. & Nagano, T. Selective zinc sensor molecules with various affinities for Zn(II), revealing dynamics and regional distribution of synaptically released Zn(II) in hippocampal slices. J. Am. Chem. Soc. 127, 10197–10204 (2005).

    CAS  PubMed  Google Scholar 

  44. Wu, Y.K. et al. Boron dipyrromethene fluorophore based fluorescence sensor for the selective imaging of Zn(II) in living cells. Org. Biomol. Chem. 3, 1387–1392 (2005).

    CAS  PubMed  Google Scholar 

  45. Wang, J.B. et al. A pH-resistant Zn(II) sensor derived from 4-aminonaphthalimide: design, synthesis and intracellular applications. J. Mater. Chem. 15, 2836–2839 (2005).

    CAS  Google Scholar 

  46. Tang, B. et al. Highly sensitive and selective near-infrared fluorescent probe for zinc and its application to macrophage cells. Chem. Commun. (Camb) 3609–3611 (2006).

  47. Kiyose, K., Kojima, H., Urano, Y. & Nagano, T. Development of a ratiometric fluorescent zinc ion probe in near-infrared region, based on tricarbocyanine chromophore. J. Am. Chem. Soc. 128, 6548–6549 (2006).

    CAS  PubMed  Google Scholar 

  48. Lim, N.C. & Bruckner, C. DPA-substituted coumarins as chemosensors for zinc(II): modulation of the chemosensory characteristics by variation of the position of the chelate on the coumarin. Chem. Commun. (Camb) 1094–1095 (2004).

  49. Lim, N.C. et al. Coumarin-based chemosensors for zinc(II): toward the determination of the design algorithm for CHEF-type and ratiometric probes. Inorg. Chem. 44, 2018–2030 (2005).

    CAS  PubMed  Google Scholar 

  50. Taki, M., Wolford, J.L. & O'Halloran, T.V. Emission ratiometric imaging of intracellular zinc: design of a benzoxazole fluorescent sensor and its application in two-photon microscopy. J. Am. Chem. Soc. 126, 712–713 (2004).

    CAS  PubMed  Google Scholar 

  51. Chang, C.J., Jaworski, J., Nolan, E.M., Sheng, M. & Lippard, S.J. A tautomeric zinc sensor for ratiometric fluorescence imaging: application to nitric oxide-induced release of intracellular zinc. Proc. Natl. Acad. Sci. USA 101, 1129–1134 (2004).

    CAS  PubMed  Google Scholar 

  52. Gee, K.R., Zhou, Z.L., Ton-That, D., Sensi, S.L. & Weiss, J.H. Measuring zinc in living cells. A new generation of sensitive and selective fluorescent probes. Cell Calcium 31, 245–251 (2002).

    CAS  PubMed  Google Scholar 

  53. MacDiarmid, C.W., Milanick, M.A. & Eide, D.J. Induction of the ZRC1 metal tolerance gene in zinc-limited yeast confers resistance to zinc shock. J. Biol. Chem. 278, 15065–15072 (2003).

    CAS  PubMed  Google Scholar 

  54. Maruyama, S., Kikuchi, K., Hirano, T., Urano, Y. & Nagano, T. A novel, cell-permeable, fluorescent probe for ratiometric imaging of zinc ion. J. Am. Chem. Soc. 124, 10650–10651 (2002).

    CAS  PubMed  Google Scholar 

  55. Henary, M.M. & Fahrni, C.J. Excited state intramolecular proton transfer and metal ion complexation of 2-(2′-hydroxyphenyl)benzazoles in aqueous solution. J. Phys. Chem. A 106, 5210–5220 (2002).

    CAS  Google Scholar 

  56. Woodroofe, C.C. & Lippard, S.J. A novel two-fluorophore approach to ratiometric sensing of Zn(II). J. Am. Chem. Soc. 125, 11458–11459 (2003).

    CAS  PubMed  Google Scholar 

  57. Woodroofe, C.C., Won, A.C. & Lippard, S.J. Esterase-activated two-fluorophore system for ratiometric sensing of biological zinc(II). Inorg. Chem. 44, 3112–3120 (2005).

    CAS  PubMed  Google Scholar 

  58. Whitaker, J.E., Haugland, R.P. & Prendergast, F.G. Spectral and photophysical studies of benzo[c]xanthene dyes: dual emission pH sensors. Anal. Biochem. 194, 330–344 (1991).

    CAS  PubMed  Google Scholar 

  59. Valentine, J.S. & Hart, P.J. Misfolded CuZnSOD and amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. USA 100, 3617–3622 (2003).

    CAS  PubMed  Google Scholar 

  60. Barnham, K.J., Masters, C.L. & Bush, A.I. Neurodegenerative diseases and oxidative stress. Nat. Rev. Drug Discov. 3, 205–214 (2004).

    CAS  PubMed  Google Scholar 

  61. Brown, D.R. & Kozlowski, H. Biological inorganic and bioinorganic chemistry of neurodegeneration based on prion and Alzheimer diseases. Dalton Trans. 1907–1917 (2004).

  62. Waggoner, D.J., Bartnikas, T.B. & Gitlin, J.D. The role of copper in neurodegenerative disease. Neurobiol. Dis. 6, 221–230 (1999).

    CAS  PubMed  Google Scholar 

  63. Vulpe, C., Levinson, B., Whitney, S., Packman, S. & Gitschier, J. Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase. Nat. Genet. 3, 7–13 (1993).

    CAS  PubMed  Google Scholar 

  64. Bull, P.C., Thomas, G.R., Rommens, J.M., Forbes, J.R. & Cox, D.W. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat. Genet. 5, 327–337 (1993).

    CAS  PubMed  Google Scholar 

  65. O'Halloran, T.V. & Culotta, V.C. Metallochaperones, an intracellular shuttle service for metal ions. J. Biol. Chem. 275, 25057–25060 (2000).

    CAS  PubMed  Google Scholar 

  66. Rosenzweig, A.C. & O'Halloran, T.V. Structure and chemistry of the copper chaperone proteins. Curr. Opin. Chem. Biol. 4, 140–147 (2000).

    CAS  PubMed  Google Scholar 

  67. Puig, S. & Thiele, D.J. Molecular mechanisms of copper uptake and distribution. Curr. Opin. Chem. Biol. 6, 171–180 (2002).

    CAS  PubMed  Google Scholar 

  68. Arnesano, F., Banci, L., Bertini, I. & Ciofi-Baffoni, S. Perspectives in inorganic structural genomics: a trafficking route for copper. Eur. J. Inorg. Chem., 1583–1593 (2004).

  69. Herd, S.M., Camakaris, J., Christofferson, R., Wookey, P. & Danks, D.M. Uptake and efflux of copper-64 in Menkes'-disease and normal continuous lymphoid cell lines. Biochem. J. 247, 341–347 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Yang, L.C. et al. Imaging of the intracellular topography of copper with a fluorescent sensor and by synchrotron x-ray fluorescence microscopy. Proc. Natl. Acad. Sci. USA 102, 11179–11184 (2005).

    CAS  PubMed  Google Scholar 

  71. Zeng, L., Miller, E.W., Pralle, A., Isacoff, E.Y. & Chang, C.J. A selective turn-on fluorescent sensor for imaging copper in living cells. J. Am. Chem. Soc. 128, 10–11 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Miller, E.W., Zeng, L., Domaille, D.W. & Chang, C.J. Preparation and use of Coppersensor-1, a synthetic fluorophore for live-cell copper imaging. Nat. Protoc. 1, 824–827 (2006).

    CAS  PubMed  Google Scholar 

  73. Hentze, M.W., Muckenthaler, M.U. & Andrews, N.C. Balancing acts: molecular control of mammalian iron metabolism. Cell 117, 285–297 (2004).

    CAS  PubMed  Google Scholar 

  74. Cricton, R.R., Wilmet, S., Legssyer, R. & Ward, R. Molecular and cellular mechanisms of iron homeostasis and toxicity in mammalian cells. J. Inorg. Biochem. 91, 9–18 (2002).

    Google Scholar 

  75. Petrat, F., Rauen, U. & de Groot, H. Determination of the chelatable iron pool of isolated rat hepatocytes by digital fluorescence microscopy using the fluorescent probe, phen green SK. Hepatology 29, 1171–1179 (1999).

    CAS  PubMed  Google Scholar 

  76. Lytton, S.D., Mester, B., Libman, J., Shanzer, A. & Cabantchik, Z.I. Monitoring of iron(III) removal from biological sources using a novel fluorescent siderophore. Anal. Biochem. 205, 326–333 (1992).

    CAS  PubMed  Google Scholar 

  77. Ma, Y., de Groot, H., Liu, Z., Hider, R.C. & Petrat, F. Chelation and determination of labile iron in primary hepatocytes by pyridinone fluorescent probes. Biochem. J. 395, 49–55 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Hua, J. & Wang, Y.G. A highly selective and sensitive fluorescent chemosensor for Fe(III) in physiological aqueous solution. Chem. Lett. (Jpn) 34, 98–99 (2005).

    CAS  Google Scholar 

  79. Xiang, Y. & Tong, A. A new rhodamine-based chemosensor exhibiting selective Fe(III)-amplified fluorescence. Org. Lett. 8, 1549–1552 (2006).

    CAS  PubMed  Google Scholar 

  80. US Environmental Protection Agency. Regulatory impact analysis of the Clean Air Mercury Rule (EPA-452/R-05-003) 1–570 (US Environmental Protection Agency, Research Triangle Park, North Carolina, USA, 2005).

  81. Flegal, A.R. & Smith, D.R. Current needs for increased accuracy and precision in measurements of low levels of lead in blood. Environ. Res. 58, 125–133 (1992).

    CAS  PubMed  Google Scholar 

  82. D'Itri, F.M. The Environmental Mercury Problem 1–124 (CRC Press, Cleveland, Ohio, USA, 1972).

    Google Scholar 

  83. Simons, T.J.B. Lead-calcium interactions in cellular lead toxicity. Neurotoxicology 14, 77–85 (1993).

    CAS  PubMed  Google Scholar 

  84. Asmuss, M., Mullenders, L.H.F. & Hartwig, A. Interference by toxic metal compounds with isolated zinc finger DNA repair proteins. Toxicol. Lett. 112113, 227–231 (2000).

    PubMed  Google Scholar 

  85. Zhou, T. et al. Cadmium at a non-toxic dose alters gene expression in mouse testes. Toxicol. Lett. 154, 191–200 (2004).

    CAS  PubMed  Google Scholar 

  86. Nolan, E.M. & Lippard, S.J. A “turn-on” fluorescent sensor for the selective detection of mercuric ion in aqueous media. J. Am. Chem. Soc. 125, 14270–14271 (2003).

    CAS  PubMed  Google Scholar 

  87. Nolan, E.M. & Lippard, S.J. Turn-on and ratiometric mercury sensing in water with a red-emitting probe. J. Am. Chem. Soc. 129, 5910–5918 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Nolan, E.M., Racine, M.E. & Lippard, S.J. Selective Hg(II) detection in aqueous solution with thiol derivatized fluoresceins. Inorg. Chem. 45, 2742–2749 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Wang, J.B. & Qian, X.H. A series of polyamide receptor based PET fluorescent sensor molecules: positively cooperative Hg(II) ion binding with high sensitivity. Org. Lett. 8, 3721–3724 (2006).

    CAS  PubMed  Google Scholar 

  90. Wang, J.B. & Qian, X.H. Two regioisomeric and exclusively selective Hg(II) sensor molecules composed of a naphthalimide fluorophore and an o-phenylenediamine derived triamide receptor. Chem. Commun. (Camb) 109–111 (2006).

  91. Guo, X., Qian, X. & Jia, L. A highly selective and sensitive fluorescent chemosensor for Hg(II) in neutral buffer aqueous solution. J. Am. Chem. Soc. 126, 2272–2273 (2004).

    CAS  PubMed  Google Scholar 

  92. Zhang, Z.C. et al. Visible study of mercuric ion and its conjugate in living cells of mammals and plants. Chem. Res. Toxicol. 18, 1814–1820 (2005).

    CAS  PubMed  Google Scholar 

  93. Yoon, S., Albers, A.E., Wong, A.P. & Chang, C.J. Screening mercury levels in fish with a selective fluorescent chemosensor. J. Am. Chem. Soc. 127, 16030–16031 (2005).

    CAS  PubMed  Google Scholar 

  94. Yoon, S., Miller, E.W., He, Q., Do, P.H. & Chang, C.J. A bright and specific fluorescent sensor for mercury in water, cells, and tissue. Angew. Chem. Int. Ed. 46, 6658–6661 (2007).

    CAS  Google Scholar 

  95. Ko, S.K., Yang, Y.K., Tae, J. & Shin, I. In vivo monitoring of mercury ions using a rhodamine-based molecular probe. J. Am. Chem. Soc. 128, 14150–14155 (2006).

    CAS  PubMed  Google Scholar 

  96. Liu, B. & Tian, H. A selective fluorescent ratiometric chemodosimeter for mercury ion. Chem. Commun. (Camb) 3156–3158 (2005).

  97. He, Q.W., Miller, E.W., Wong, A.P. & Chang, C.J. A selective fluorescent sensor for detecting lead in living cells. J. Am. Chem. Soc. 128, 9316–9317 (2006).

    CAS  PubMed  Google Scholar 

  98. Gunnlaugsson, T., Lee, T.C. & Parkesh, R. Highly selective fluorescent chemsensors for cadmium in water. Tetrahedron 60, 11239–11249 (2004).

    CAS  Google Scholar 

  99. Peng, X.J. et al. A selective fluorescent sensor for imaging Cd(II) in living cells. J. Am. Chem. Soc. 129, 1500–1501 (2007).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the University of California, Berkeley, the Dreyfus Foundation, the Beckman Foundation, the American Federation for Aging Research, the Packard Foundation, the Sloan Foundation, the US National Science Foundation (CAREER CHE-0548245) and the US National Institute of General Medical Sciences (NIH GM 79465) for funding our laboratory's work on metal sensors. D.W.D. thanks the Chemical Biology Graduate Program sponsored by the US National Institutes of Health (T32 GM066698) for support, and E.L.Q. acknowledges a Branch graduate fellowship from the University of California, Berkeley.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christopher J Chang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Domaille, D., Que, E. & Chang, C. Synthetic fluorescent sensors for studying the cell biology of metals. Nat Chem Biol 4, 168–175 (2008). https://doi.org/10.1038/nchembio.69

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.69

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing