Journal of Fluorescence

, Volume 24, Issue 6, pp 1671–1677 | Cite as

A Highly Selective Turn-on Fluorescent Chemodosimeter for Cu2+ Through a Cu2+-Promoted Redox Reaction



A highly sensitive and selective photoinduced electron transfer (PET) fluorescence chemodosimeter L for Cu2+ detection has been synthesized and characterized. This PET chemosensor composed of a butano-tethered electron-riched phenothiazine (Ptz) donor and acridine orange (AO) signalling element. Based on the Cu2+-promoted oxidation of Ptz donor, the signalling element AO showed a unique fluorescent turn-on properties, which led to a highly Cu2+-specific fluorescent chemodosimeter. A fluorescent enhancement factor over 8-fold can be reached by fully blocking the PET channel with a detection limit down to the 10−7 M range. Meanwhile, the reversibility of the chemodosimeter L can be realized by the addition of L-cysteine.

Graphical Abstract

Based on the Cu2+-promoted oxidation of the electron-donating phenothiazine (Ptz) moiety, the property of fluorescent signal recovery of the acridine orange (AO) fluorophore has been developed as a highly selective turn-on fluorescent chemodosimeter for Cu (II).


Fluorescence spectroscopy Sensor Acridine orange Copper ion Redox reaction 



We gratefully acknowledge the Natural Science Foundation of China (NNSFC 21272172), the Program for New Century Excellent Talents in University (NCET-09-0894) and the Natural Science Foundation of Tianjin (12JCZDJC21000).

Supplementary material

10895_2014_1454_MOESM1_ESM.doc (1.3 mb)
ESM 1 (DOC 1372 kb)


  1. 1.
    Krämer R (1998) Fluorescent chemosensors for Cu2+ ions: fast, selective, and highly sensitive. Angew Chem Int Ed 37:772–773CrossRefGoogle Scholar
  2. 2.
    Li X, Gao X, Shi W, Ma H (2014) Design strategies for water-soluble small molecular chromogenic and fluorogenic probes. Chem Rev 114:590–659PubMedCrossRefGoogle Scholar
  3. 3.
    De Silva AP, Gunaratne HN, Gunnlaugsson T, Huxley AJM, McCoy CP, Rademacher JT, Rice TE (1997) Signaling recognition events with fluorescent sensors and switches. Chem Rev 97:1515–1566PubMedCrossRefGoogle Scholar
  4. 4.
    Chang J, Lu Y, He S, Liu C, Zhao LC, Zeng XS (2013) Efficient fluorescent chemosensor for HSO4 based on a strategy of anion-induced rotation-displaced H-aggregate. Chem Commun 49:6259–6261CrossRefGoogle Scholar
  5. 5.
    Da Silva JJRF, Williams RJP (2001) The biological chemistry of the elements: the inorganic chemistry of life [M]. Oxford University PressGoogle Scholar
  6. 6.
    Vulpe C, Levinson B, Whitney S, Packman S, Gitschier J (1993) Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase. Nat Genet 3:7–13PubMedCrossRefGoogle Scholar
  7. 7.
    Bruijn LI, Miller TM, Cleveland DW (2004) Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu Rev Neurosci 27:723–749PubMedCrossRefGoogle Scholar
  8. 8.
    Valentine JS, Hart PJ (2003) Misfolded CuZnSOD and amyotrophic lateral sclerosis. PNAS 100:3617–3622PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Barnham KJ, Masters CL, Bush AI (2004) Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov 3:205–214PubMedCrossRefGoogle Scholar
  10. 10.
    Brown DR, Kozlowski H (2004) Biological inorganic and bioinorganic chemistry of neurodegeneration based on prion and Alzheimer diseases. Dalton Trans 1907–1917Google Scholar
  11. 11.
    Deraeve C, Boldron C, Maraval A, Mazarguil H, Gornitzka H, Vendier L, Pitie M, Meunier B (2008) Preparation and study of new poly-8-hydroxyquinoline chelators for an anti-Alzheimer strategy. Chem Eur J 14:682–696PubMedCrossRefGoogle Scholar
  12. 12.
    Uauy R, Olivares M, Gonzalez M (1998) Essentiality of copper in humans. Am J Clin Nutr 67:952S–959SPubMedGoogle Scholar
  13. 13.
    Torrado A, Walkup GK, Imperiali B (1998) Exploiting polypeptide motifs for the design of selective Cu (II) ion chemosensors. J Am Chem Soc 120:609–610CrossRefGoogle Scholar
  14. 14.
    Zheng Y, Gattás-Asfura KM, Konka V, Leblanc RM (2002) A dansylated peptide for the selective detection of copper ions. Chem Commun:2350–2351Google Scholar
  15. 15.
    Zheng Y, Orbulescu J, Ji X, Andreopoulos FM, Pham SM, Leblanc RM (2003) Development of fluorescent film sensors for the detection of divalent copper. J Am Chem Soc 125:2680–2686PubMedCrossRefGoogle Scholar
  16. 16.
    Gattás-Asfura KM, Leblanc RM (2003) Peptide-coated CdS quantum dots for the optical detection of copper (II) and silver (I). Chem Commun: 2684–2685Google Scholar
  17. 17.
    Royzen M, Dai Z, Canary JW (2005) Ratiometric displacement approach to Cu (II) sensing by fluorescence. J Am Chem Soc 127:1612–1613PubMedCrossRefGoogle Scholar
  18. 18.
    Gunnlaugsson T, Leonard JP, Murray NS (2004) Highly selective colorimetric naked-eye Cu (II) detection using an azobenzene chemosensor. Org Lett 6:1557–1560PubMedCrossRefGoogle Scholar
  19. 19.
    Rurack K, Kollmannsberger M, Resch-Genger U, Daub J (2000) A selective and sensitive fluoroionophore for Hg (II), Ag (I), and Cu (II) with virtually decoupled fluorophore and receptor units. J Am Chem Soc 122:968–969CrossRefGoogle Scholar
  20. 20.
    Irving HM, Williams RJP (1953) The stability of transition-metal complexes. J Chem Soc: 3192–3210Google Scholar
  21. 21.
    Khan M, Bouet G, Vierling F, Meullemeestre J, Schwing MJ (1996) Formation of cobalt (II), nickel (II) and copper (II) chloro complexes in alcohols and the Irving-Williams order of stabilities. Trans Metal Chem 21:231–234CrossRefGoogle Scholar
  22. 22.
    Grandini P, Mancin F, Tecilla P, Scrimin P, Tonellato U (1999) Exploiting the self-assembly strategy for the design of selective Cu (II) ion chemosensors. Angew Chem Int Ed 38:3061–3064CrossRefGoogle Scholar
  23. 23.
    Shnek DR, Pack DW, Arnold FH, Sasaki DY (1995) Metal-induced dispersion of lipid aggregates: a simple, selective, and sensitive fluorescent metal ion sensor. Angew Chem Int Ed Engl 34:905–907CrossRefGoogle Scholar
  24. 24.
    Bodenant B, Weil T, Businelli-Pourcel M, Fages F, Barbe B, Pianet I, Laguerre M (1999) Synthesis and solution structure analysis of a bispyrenyl bishydroxamate calix [4] arene-based receptor, a fluorescent chemosensor for Cu2+ and Ni2+ metal ions. J Org Chem 64:7034–7039CrossRefGoogle Scholar
  25. 25.
    Klein G, Kaufmann D, Schürch S, Reymond JL (2001) A fluorescent metal sensor based on macrocyclic chelation Electronic supplementary information (ESI) available: electrospray MS data and photographs of solutions of ligand 3c in the absence and presence of Cu2+. Chem Commun:561–562Google Scholar
  26. 26.
    Zheng Y, Cao X, Orbulescu J, Konka V, Andreopoulos FM, Pham SM, Leblanc RM (2003) Peptidyl fluorescent chemosensors for the detection of divalent copper. Anal Chem 75:1706–1712PubMedCrossRefGoogle Scholar
  27. 27.
    Comba P, Krämer R, Mokhir A, Naing K, Schatz E (2006) Synthesis of new phenanthroline-based heteroditopic ligands-highly efficient and selective fluorescence sensors for copper (II) ions. Eur J Inorg Chem: 4442–4448Google Scholar
  28. 28.
    White BR, Holcombe JA (2007) Fluorescent peptide sensor for the selective detection of Cu2+. Talanta 71:2015–2020PubMedCrossRefGoogle Scholar
  29. 29.
    Mahapatra AK, Hazra G, Das NK, Goswami S (2011) A highly selective triphenylamine-based indolylmethane derivatives as colorimetric and turn-off fluorimetric sensor toward Cu2+ detection by deprotonation of secondary amines. Sen Actuators B Chem 156:456–462CrossRefGoogle Scholar
  30. 30.
    Mashraqui SH, Chandiramani M, Betkar R, Ghorpade S (2010) An easily accessible internal charge transfer chemosensor exhibiting dual colorimetric and luminescence switch on responses for targeting Cu2+. Sen Actuators B Chem 150:574–578Google Scholar
  31. 31.
    Lee A, Chin J, Park OK, Chung H, Kim JW, Yoon SY, Park K (2013) A novel near-infrared fluorescence chemosensor for copper ion detection using click ligation and energy transfer. Chem Commun 49:5969–5971CrossRefGoogle Scholar
  32. 32.
    Lee YH, Park N, Park YB, Hwang YJ, Kang C, Kim JS (2014) Organelle-selective fluorescent Cu2+ ion probes: revealing the endoplasmic reticulum as a reservoir for Cu-overloading. Chem Commun 50:3197–3200CrossRefGoogle Scholar
  33. 33.
    Zhao Y, Zhang XB, Han ZX, Qiao L, Li CY, Jian LX, Shen JL, Yu RQ (2009) Highly sensitive and selective colorimetric and Off-On fluorescent chemosensor for Cu2+ in aqueous solution and living cells. Anal Chem 81:7022–7030PubMedCrossRefGoogle Scholar
  34. 34.
    Kumar M, Kumar N, Bhalla V, Sharma PR, Kaur T (2011) Highly selective fluorescence turn-on chemodosimeter based on rhodamine for nanomolar detection of copper ions. Org Lett 14:406–409PubMedCrossRefGoogle Scholar
  35. 35.
    Huang J, Xu Y, Qian X (2009) A colorimetric sensor for Cu2+ in aqueous solution based on metal ion-induced deprotonation: deprotonation/protonation mediated by Cu2+-ligand interactions. Dalton Trans:1761–1766Google Scholar
  36. 36.
    He Q, Miller EW, Wong AP, Chang CJ (2006) A selective fluorescent sensor for detecting lead in living cell. J Am Chem Soc 128:9316–9317PubMedCrossRefGoogle Scholar
  37. 37.
    Martínez R, Zapata F, Caballero A, Espinosa A, Tárraga A, Molina P (2006) 2-Aza-1,3-butadiene derivatives featuring an anthracene or pyrene unit: highly selective colorimetric and fluorescent signaling of Cu2+ cation. Org Lett 8:3235–3238PubMedCrossRefGoogle Scholar
  38. 38.
    Kim SH, Kim JS, Park SM, Chang SK (2006) Hg2+-selective OFF-ON and Cu2+-selective ON-OFF type fluoroionophore based upon cyclam. Org Lett 8:371–374PubMedCrossRefGoogle Scholar
  39. 39.
    Xu Z, Xiao Y, Qian X, Cui J, Cui D (2005) Ratiometric and selective fluorescent sensor for Cu (II) based on internal charge transfer (ICT). Org Lett 7:889–892PubMedCrossRefGoogle Scholar
  40. 40.
    Kaur S, Kumar S (2002) Photoactive chemosensors 3: a unique case of fluorescence enhancement with Cu (II). Chem Commun: 2840–2841Google Scholar
  41. 41.
    Ghosh P, Bharadwaj PK, Mandal S, Ghosh S (1996) Ni (II), Cu (II), and Zn (II) cryptate-enhanced fluorescence of a trianthrylcryptand: a potential molecular photonic OR operator. J Am Chem Soc 118:1553–1554CrossRefGoogle Scholar
  42. 42.
    Dujols V, Ford F, Czarnik AW (1997) A long-wavelength fluorescent chemodosimeter selective for Cu (II) ion in water. J Am Chem Soc 119:7386–7387CrossRefGoogle Scholar
  43. 43.
    Ramachandram B, Samanta A (1998) Transition metal ion induced fluorescence enhancement of 4-(N, N-dimethylethylenediamino)-7-nitrobenz-2-oxa-1,3-diazole. J Phys Chem A 102:10579–10587CrossRefGoogle Scholar
  44. 44.
    Wu Q, Anslyn EV (2004) Catalytic signal amplification using a heck reaction. An example in the fluorescence sensing of Cu (II). J Am Chem Soc 126:14682–14683PubMedCrossRefGoogle Scholar
  45. 45.
    Mokhir A, Kiel A, Herten DP, Kraemer R (2005) Fluorescent sensor for Cu2+ with a tunable emission wavelength. Inorg Chem 44:5661–5666PubMedCrossRefGoogle Scholar
  46. 46.
    He X, Liu H, Li Y, Wang S, Li Y, Wang N, XiaoJ XX, Zhu D (2005) Gold nanoparticle-based fluorometric and colorimetric sensing of copper (II) ions. Adv Mater 17:2811–2815CrossRefGoogle Scholar
  47. 47.
    Yang H, Liu ZQ, Zhou ZG, Shi EX, Li FY, Du YK, Yi T, Huang CH (2006) Highly selective ratiometric fluorescent sensor for Cu (II) with two urea groups. Tetrahedron Lett 47:2911–2914CrossRefGoogle Scholar
  48. 48.
    Li KB, Wei XL, Zang Y, He XP, Chen GR, Li J, Chen K (2013) Revisit of a dipropargyl rhodamine probe reveals its alternative ion sensitivity in both a solution and live cells. Analyst 138:7087–7089PubMedCrossRefGoogle Scholar
  49. 49.
    Keene FR (1999) Metal-ion promotion of the oxidative dehydrogenation of coordinated amines and alcohols. Coord Chem Rev 187:121–149CrossRefGoogle Scholar
  50. 50.
    Chaudhry AF, Mandal S, Hardcastle KI, Fahrni CJ (2011) High-contrast Cu (I)-selective fluorescent probes based on synergistic electronic and conformational switching. Chem Sci 2:1016–1024PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Quang DT, Kim JS (2010) Fluoro- and chromogenic chemodosimeters for heavy metal ion detection in solution and bio specimens. Chem Rev 110:6280–6301CrossRefGoogle Scholar
  52. 52.
    Yang Y, Zhao Q, Feng W, Li F (2013) Luminescent chemodosimeters for bio imaging. Chem Rev 113:192–270PubMedCrossRefGoogle Scholar
  53. 53.
    Ajayakumar G, Sreenath K, Gopidas KR (2009) Phenothiazine attached Ru (bpy)3 2+ derivative as highly selective “turn-ON” luminescence chemodosimeter for Cu2+. Dalton Trans:1180–1186Google Scholar
  54. 54.
    Ye Z, Song B, Yin Y, Zhang R, Yuan J (2013) Development of singlet oxygen-responsive phosphorescent ruthenium (II) complexes. Dalton Trans 42:14380–14383PubMedCrossRefGoogle Scholar
  55. 55.
    Agiamarnioti K, Triantis T, Papadopoulos K, Dimotikali D (2004) Synthesis and chemiluminescent properties of novel biotinylated acridinium esters. Acta Chim Slov 51:67–76Google Scholar
  56. 56.
    Ferguson J, Mau AWH (1973) Spontaneous and stimulated emission from dyes-spectroscopy of neutral molecules of acridine-orange, proflavine, and rhodamine-B. Aust J Chem 26:1617–1624CrossRefGoogle Scholar
  57. 57.
    Zhou Y, Kim YS, Shi J, Jacobson O, Chen XY, Liu S (2011) Evaluation of 64Cu-labeled acridinium cation: a PET radiotracer targeting tumor mitochondria. Bioconjugate Chem 22:700–708CrossRefGoogle Scholar
  58. 58.
    Lerman LS (1961) Structural considerations in the interaction of DNA and acridines. J Mol Biol 3:18–IN14PubMedCrossRefGoogle Scholar
  59. 59.
    Falcone RD, Correa NM, Biasutti MA, Silber JJ (2006) The use of acridine orange base (AOB) as molecular probe to characterize nonaqueous AOT reverse micelles. J Colloid Interf Sci 296:356–364CrossRefGoogle Scholar
  60. 60.
    Nafisi S, Saboury AA, Keramat N, Neault JF, Tajmir-Riahi HA (2007) Stability and structural features of DNA intercalation with ethidium bromide, acridine orange and methylene blue. J Mol Struct 827:35–43CrossRefGoogle Scholar
  61. 61.
    Pastré D, Piétrement O, Zozime A, Le Cam E (2005) Study of the DNA/ethidium bromide interactions on mica surface by atomic force microscope: influence of the surface friction. Biopolymers 77:53–62PubMedCrossRefGoogle Scholar
  62. 62.
    MoradpourHafshejani S, Hedley JH, Haigh AO, Pike AR, Tuite EM (2013) Synthesis and binding of proflavine diazides as functional intercalators for directed assembly on DNA. RSC Adv 3:18164–18172CrossRefGoogle Scholar
  63. 63.
    Jenekhe SA, Lu L, Alam MM (2001) New conjugated polymers with donor-acceptor architectures: Synthesis and photophysics of carbazole-quinoline and phenothiazine-quinoline copolymers and oligomers exhibiting large intramolecular charge transfer. Macromolecules 34:7315–7324CrossRefGoogle Scholar
  64. 64.
    Li H, Kim FS, Ren G, Jenekhe SA (2013) High-mobility n-type conjugated polymers based on electron-deficient tetraazabenzodifluoranthene diimide for organic electronics. J Am Chem Soc 135:14920–14923PubMedCrossRefGoogle Scholar
  65. 65.
    Du P, Lippard SJ (2010) A highly selective turn-on colorimetric, red fluorescent sensor for detecting mobile zinc in living cells. Inorg Chem 49:10753–10755PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Cai ST, Lu Y, He S, Wei F, Zhao LC, Zeng XS (2013) A highly sensitive and selective turn-on fluorescent chemosensor for palladium based on a phosphine-rhodamine conjugate. Chem Commun 49:822–824CrossRefGoogle Scholar
  67. 67.
    Shortreed M, Kopelman R, Kuhn M, Hoyland B (1996) Fluorescent fiber-optic calcium sensor for physiological measurements. Anal Chem 68:1414–1418PubMedCrossRefGoogle Scholar
  68. 68.
    Garrett CE, Prasad K (2004) The art of meeting palladium specifications in active pharmaceutical ingredients produced by Pd-catalyzed reactions. Adv Syn & Cat 346:889–900CrossRefGoogle Scholar
  69. 69.
    Pharmacopoeia of People’s Republic of China. 2010, page 52, 59, 68Google Scholar
  70. 70.
    Jacob C, Giles GI, Giles NM, Sies H (2003) Sulfur and selenium: the role of oxidation state in protein structure and function. Angew Chem Int Ed 42:4742–4758CrossRefGoogle Scholar
  71. 71.
    Allen SE, Walvoord RR, Padilla-Salinas R, Kozlowski MC (2013) Aerobic copper-catalyzed organic reactions. Chem Rev 113:6234–6458PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.School of Materials Science & Engineering, Institute of Information Functional Materials& DevicesHarbin Institute of TechnologyHarbinChina
  2. 2.School of Materials Science & EngineeringTianjin University of TechnologyTianjinChina

Personalised recommendations