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The mechanisms of boronate ester formation and fluorescent turn-on in ortho-aminomethylphenylboronic acids


ortho-Aminomethylphenylboronic acids are used in receptors for carbohydrates and various other compounds containing vicinal diols. The presence of the o-aminomethyl group enhances the affinity towards diols at neutral pH, and the manner in which this group plays this role has been a topic of debate. Further, the aminomethyl group is believed to be involved in the turn-on of the emission properties of appended fluorophores upon diol binding. In this treatise, a uniform picture emerges for the role of this group: it primarily acts as an electron-withdrawing group that lowers the pKa of the neighbouring boronic acid thereby facilitating diol binding at neutral pH. The amine appears to play no role in the modulation of the fluorescence of appended fluorophores in the protic-solvent-inserted form of the boronic acid/boronate ester. Instead, fluorescence turn-on can be consistently tied to vibrational-coupled excited-state relaxation (a loose-bolt effect). Overall, this Review unifies and discusses the existing data as of 2019 whilst also highlighting why o-aminomethyl groups are so widely used, and the role they play in carbohydrate sensing using phenylboronic acids.

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Fig. 1: Chemical reactions and primary data relevant to the topics discussed in this Review.
Fig. 2: The assignment of pKa values that would be associated with the three mechanistic postulates described in this Review.
Fig. 3
Fig. 4: Mechanistic considerations for the role of the o-aminomethyl group.
Fig. 5: Reactions and data relevant to the discussion of photophysics of the systems described in this Review.
Fig. 6: Further data and reactions related to the photophysics of the systems described in this Review.


  1. 1.

    Anslyn, E. V. & Dougherty, D. A. Modern Physical Organic Chemistry (University Science Books, 2006).

  2. 2.

    Scholz, F. et al. Crystal structure determination of the nonclassical 2-norbornyl cation. Science 341, 62–64 (2013).

    CAS  PubMed  Google Scholar 

  3. 3.

    Reinhoudt, D. N., Rudkevich, D. M. & de Jong, F. Kinetic Analysis of the Rebek self-replicating system: is there a controversy? J. Am. Chem. Soc. 118, 6880–6889 (1996).

    CAS  Google Scholar 

  4. 4.

    Cleland, W. Low-barrier hydrogen bonds and enzymatic catalysis. Arch. Biochem. Biophys. 382, 1–5 (2000).

    CAS  PubMed  Google Scholar 

  5. 5.

    Schutz, C. N. & Warshel, A. The low barrier hydrogen bond (LBHB) proposal revisited: the case of the Asp···His pair in serine proteases. Proteins 55, 711–723 (2004).

    CAS  PubMed  Google Scholar 

  6. 6.

    Hall, D. G. Boronic Acids: Preparation, Applications in Organic Synthesis and Medicine (John Wiley and Sons, 2006).

  7. 7.

    Bull, S. D. et al. Exploiting the reversible covalent bonding of boronic acids: recognition, sensing, and assembly. Acc. Chem. Res. 46, 312–326 (2013).

    CAS  PubMed  Google Scholar 

  8. 8.

    Guo, Z., Shin, I. & Yoon, J. Recognition and sensing of various species using boronic acid derivatives. Chem. Commun. 48, 5956–5967 (2012).

    CAS  Google Scholar 

  9. 9.

    Fang, H., Kaur, G. & Wang, B. Progress in boronic acid-based fluorescent glucose sensors. J. Fluoresc. 14, 481–489 (2004).

    CAS  PubMed  Google Scholar 

  10. 10.

    Heagy, M. D. & Meka, R. K. in Comprehensive Supramolecular Chemistry II (ed. Atwood, J. L.) Ch. 4.19, 615–647 (Elsevier, 2017).

  11. 11.

    Kelly, A. M., Pérez-Fuertes, Y., Arimori, S., Bull, S. D. & James, T. D. Simple protocol for NMR analysis of the enantiomeric purity of diols. Org. Lett. 8, 1971–1974 (2006).

    CAS  PubMed  Google Scholar 

  12. 12.

    Pérez-Fuertes, Y. et al. Simple protocol for NMR analysis of the enantiomeric purity of primary amines. Org. Lett. 8, 609–612 (2006).

    PubMed  Google Scholar 

  13. 13.

    Cambre, J. N. & Sumerlin, B. S. Biomedical applications of boronic acid polymers. Polymer 52, 4631–4643 (2011).

    CAS  Google Scholar 

  14. 14.

    Fujita, N., Shinkai, S. & James, T. D. Boronic acids in molecular self‐assembly. Chem. Eur. J. 3, 1076–1091 (2008).

    CAS  Google Scholar 

  15. 15.

    Nishiyabu, R., Kubo, Y., James, T. D. & Fossey, J. S. Boronic acid building blocks: tools for self assembly. Chem. Commun. 47, 1124–1150 (2011).

    CAS  Google Scholar 

  16. 16.

    Dai, C. et al. Using boronolectin in MALDI-MS imaging for the histological analysis of cancer tissue expressing the sialyl Lewis X antigen. Chem. Commun. 47, 10338–10340 (2011).

    CAS  Google Scholar 

  17. 17.

    Sun, X., Zhai, W., Fossey, J. S. & James, T. D. Boronic acids for fluorescence imaging of carbohydrates. Chem. Commun. 52, 3456–3469 (2016).

    CAS  Google Scholar 

  18. 18.

    Sun, X. et al. Reaction-based Indicator displacement Assay (RIA) for the selective colorimetric and fluorometric detection of peroxynitrite. Chem. Sci. 6, 2963–2967 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Sun, X. et al. “Integrated” and “insulated” boronate-based fluorescent probes for the detection of hydrogen peroxide. Chem. Commun. 49, 8311–8313 (2013).

    CAS  Google Scholar 

  20. 20.

    Chan, J., Dodani, S. C. & Chang, C. J. Reaction-based small-molecule fluorescent probes for chemoselective bioimaging. Nat. Chem. 4, 973–984 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Lippert, A. R., Van de Bittner, G. C. & Chang, C. J. Boronate oxidation as a bioorthogonal reaction approach for studying the chemistry of hydrogen peroxide in living systems. Acc. Chem. Res. 44, 793–804 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    James, T. & Shinkai, S. in Topics in Current Chemistry (ed. Penadés, S.) Vol. 218, Ch. 6, 159–200 (Springer, 2002).

  23. 23.

    James, T. D., Phillips, M. D. & Shinkai, S. Boronic Acids in Saccharide Recognition (Royal Society of Chemistry, 2006).

  24. 24.

    James, T. D., Sandanayake, K. R. A. S. & Shinkai, S. Saccharide sensing with molecular receptors based on boronic acid. Angew. Chem. Int. Ed. Engl. 35, 1910–1922 (1996).

    Google Scholar 

  25. 25.

    Jin, S., Cheng, Y., Reid, S., Li, M. & Wang, B. Carbohydrate recognition by boronolectins, small molecules, and lectins. Med. Res. Rev. 30, 171–257 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Wright, A. T. et al. Differential receptors create patterns that distinguish various proteins. Angew. Chem. Int. Ed. 44, 6375–6378 (2005).

    CAS  Google Scholar 

  27. 27.

    Bicker, K. L. et al. Synthetic lectin arrays for the detection and discrimination of cancer associated glycans and cell lines. Chem. Sci. 3, 1147–1156 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Gray, C. W. & Houston, T. A. Boronic acid receptors for α-hydroxycarboxylates: high affinity of Shinkai’s glucose receptor for tartrate. J. Org. Chem. 67, 5426–5428 (2002).

    CAS  PubMed  Google Scholar 

  29. 29.

    Wang, W., Gao, X. & Wang, B. Boronic acid-based sensors. Curr. Org. Chem. 6, 1285–1317 (2002).

    CAS  Google Scholar 

  30. 30.

    Lee, J. W., Lee, J.-S. & Chang, Y.-T. Colorimetric Identification of carbohydrates by a pH indicator/pH change inducer ensemble. Angew. Chem. Int. Ed. 45, 6485–6487 (2006).

    CAS  Google Scholar 

  31. 31.

    Schiller, A., Wessling, R. A. & Singaram, B. A Fluorescent sensor array for saccharides based on boronic acid appended bipyridinium salts. Angew. Chem. Int. Ed. 46, 6457–6459 (2007).

    CAS  Google Scholar 

  32. 32.

    Edwards, N. Y., Sager, T. W., McDevitt, J. T. & Anslyn, E. V. Boronic acid based peptidic receptors for pattern-based saccharide sensing in neutral aqueous media, an application in real-life samples. J. Am. Chem. Soc. 129, 13575–13583 (2007).

    CAS  PubMed  Google Scholar 

  33. 33.

    Musto, C. J., Lim, S. H. & Suslick, K. S. Colorimetric detection and identification of natural and artificial sweeteners. Anal. Chem. 81, 6526–6533 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Zhang, X., You, L., Anslyn, E. V. & Qian, X. Discrimination and classification of ginsenosides and ginsengs using bis-boronic acid receptors in dynamic multicomponent indicator displacement sensor arrays. Chem. Eur. J. 18, 1102–1110 (2012).

    CAS  PubMed  Google Scholar 

  35. 35.

    Springsteen, G. & Wang, B. A detailed examination of boronic acid–diol complexation. Tetrahedron 58, 5291–5300 (2002).

    CAS  Google Scholar 

  36. 36.

    Zaubitzer, F., Buryak, A. & Severin, K. Cp*Rh-based indicator-displacement assays for the identification of amino sugars and aminoglycosides. Chem. Eur. J. 12, 3928–3934 (2006).

    CAS  PubMed  Google Scholar 

  37. 37.

    Yasuda, H., Kurokáwa, T., Fujii, Y., Yamashita, A. & Ishibashi, S. Decreased d-glucose transport across renal brush-border membrane vesicles from streptozotocin-induced diabetic rats. Biochim. Biophys. Acta Biomembr. 1021, 114–118 (1990).

    CAS  Google Scholar 

  38. 38.

    Fedorak, R. N., Gershon, M. D. & Field, M. Induction of intestinal glucose carriers in streptozocin-treated chronically diabetic rats. Gastroenterology 96, 37–44 (1989).

    CAS  PubMed  Google Scholar 

  39. 39.

    Mallia, A. K., Hermanson, G. T., Krohn, R. I., Fujimoto, E. K. & Smith, P. K. Preparation and use of a boronic acid affinity support for separation and quantitation of glycosylated hemoglobins. Anal. Lett. 14, 649–661 (1981).

    CAS  Google Scholar 

  40. 40.

    Yang, W. et al. Diboronic acids as fluorescent probes for cells expressing sialyl Lewis X. Biorg. Med. Chem. Lett. 12, 2175–2177 (2002).

    CAS  Google Scholar 

  41. 41.

    Sun, X. & James, T. D. Glucose sensing in supramolecular chemistry. Chem. Rev. 115, 8001–8037 (2015).

    CAS  PubMed  Google Scholar 

  42. 42.

    Goldberg, R. N. & Tewari, Y. B. Thermodynamic and transport properties of carbohydrates and their monophosphates: the pentoses and hexoses. J. Phys. Chem. Ref. Data 18, 809–880 (1989).

    CAS  Google Scholar 

  43. 43.

    Cesàro, A. in Thermodynamic Data for Biochemistry and Biotechnology 177–207 (Springer, 1986).

  44. 44.

    Franks, F. Physical chemistry of small carbohydrates-equilibrium solution properties. Pure Appl. Chem. 59, 1189–1202 (1987).

    CAS  Google Scholar 

  45. 45.

    Essentials of Glycobiology 2nd edn (eds. Varki, A. et al.) 23–36 (Cold Spring Harbor Laboratory Press, 2009).

  46. 46.

    Moulin, E., Cormos, G. & Giuseppone, N. Dynamic combinatorial chemistry as a tool for the design of functional materials and devices. Chem. Soc. Rev. 41, 1031–1049 (2012).

    CAS  PubMed  Google Scholar 

  47. 47.

    Lehn, J.-M. From supramolecular chemistry towards constitutional dynamic chemistry and adaptive chemistry. Chem. Soc. Rev. 36, 151–160 (2007).

    CAS  PubMed  Google Scholar 

  48. 48.

    Lehn, J.-M. Supramolecular Chemistry: Concepts and Perspectives (Vch, 1995).

  49. 49.

    Rowan, S. J., Cantrill, S. J., Cousins, G. R., Sanders, J. K. & Stoddart, J. F. Dynamic covalent chemistry. Angew. Chem. Int. Ed. 41, 898–952 (2002).

    Google Scholar 

  50. 50.

    Corbett, P. T. et al. Dynamic combinatorial chemistry. Chem. Rev. 106, 3652–3711 (2006).

    CAS  PubMed  Google Scholar 

  51. 51.

    Cougnon, F. B. L. & Sanders, J. K. M. Evolution of dynamic combinatorial chemistry. Acc. Chem. Res. 45, 2211–2221 (2012).

    CAS  PubMed  Google Scholar 

  52. 52.

    Wilson, A., Gasparini, G. & Matile, S. Functional systems with orthogonal dynamic covalent bonds. Chem. Soc. Rev. 43, 1948–1962 (2014).

    CAS  PubMed  Google Scholar 

  53. 53.

    Weith, H. L., Wiebers, J. L. & Gilham, P. T. Synthesis of cellulose derivatives containing the dihydroxyboryl group and a study of their capacity to form specific complexes with sugars and nucleic acid components. Biochemistry 9, 4396–4401 (1970).

    CAS  PubMed  Google Scholar 

  54. 54.

    Hirata, O., Kubo, Y., Takeuchi, M. & Shinkai, S. Mono- and oligosaccharide sensing by phenylboronic acid-appended 5,15-bis(diarylethynyl)porphyrin complexes. Tetrahedron 60, 11211–11218 (2004).

    CAS  Google Scholar 

  55. 55.

    Wulff, G. Selective binding to polymers via covalent bonds. The construction of chiral cavities as specific receptor sites. Pure Appl. Chem. 54, 2093–2102 (1982).

    Google Scholar 

  56. 56.

    Wulff, G., Dederichs, W., Grotstollen, R. & Jupe, C. in Affinity Chromatography and Related Techniques 207–216 (Elsevier, 1982).

  57. 57.

    Lorand, J. P. & Edwards, J. O. Polyol complexes and structure of the benzeneboronate ion. J. Org. Chem. 24, 769–774 (1959).

    CAS  Google Scholar 

  58. 58.

    Wulff, G., Lauer, M. & Böhnke, H. Rapid proton transfer as cause of an unusually large neighboring group effect. Angew. Chem. Int. Ed. Engl. 23, 741–742 (1984).

    Google Scholar 

  59. 59.

    Jin, S., Wang, J., Li, M. & Wang, B. Synthesis, evaluation, and computational studies of naphthalimide-based long-wavelength fluorescent boronic acid reporters. Chem. Eur. J. 14, 2795–2804 (2008).

    CAS  PubMed  Google Scholar 

  60. 60.

    Zhu, L. et al. A structural investigation of the N−B Interaction in an o-(N,N-dialkylaminomethyl)arylboronate system. J. Am. Chem. Soc. 128, 1222–1232 (2006).

    CAS  PubMed  Google Scholar 

  61. 61.

    Zhai, W., Sun, X., James, T. D. & Fossey, J. S. Boronic acid‐based carbohydrate sensing. Chem. Asian J. 10, 1836–1848 (2015).

    CAS  PubMed  Google Scholar 

  62. 62.

    James, T. D., Sandanayake, K. R. A. S. & Shinkai, S. Novel photoinduced electron-transfer sensor for saccharides based on the interaction of boronic acid and amine. J. Chem. Soc. Chem. Commun. 1994, 477–478 (1994).

    Google Scholar 

  63. 63.

    James, T. D., Sandanayake, K. R. A. S. & Shinkai, S. A glucose-selective molecular fluorescence sensor. Angew. Chem. Int. Ed. Engl. 33, 2207–2209 (1994).

    Google Scholar 

  64. 64.

    Franzen, S., Ni, W. & Wang, B. Study of the mechanism of electron-transfer quenching by boron−nitrogen adducts in fluorescent sensors. J. Phys. Chem. B 107, 12942–12948 (2003).

    CAS  Google Scholar 

  65. 65.

    Ni, W., Kaur, G., Springsteen, G., Wang, B. & Franzen, S. Regulating the fluorescence intensity of an anthracene boronic acid system: a B–N bond or a hydrolysis mechanism? Bioorg. Chem. 32, 571–581 (2004).

    CAS  PubMed  Google Scholar 

  66. 66.

    Chapin, B. M. et al. Disaggregation is a mechanism for emission turn-on of ortho-aminomethylphenylboronic acid-based saccharide sensors. J. Am. Chem. Soc. 139, 5568–5578 (2017).

    CAS  PubMed  Google Scholar 

  67. 67.

    Crane, B. C. et al. The development of a continuous intravascular glucose monitoring sensor. J. Diabetes Sci. Technol. 9, 751–761 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Sun, X., James, T. D. & Anslyn, E. V. Arresting “loose bolt” internal conversion from −B(OH)2 groups is the mechanism for emission turn-on in ortho-aminomethylphenylboronic acid-based saccharide sensors. J. Am. Chem. Soc. 140, 2348–2354 (2018).

    CAS  PubMed  Google Scholar 

  69. 69.

    James, T. D., Samankumara Sandanayake, K. R. A. & Shinkai, S. Chiral discrimination of monosaccharides using a fluorescent molecular sensor. Nature 374, 345–347 (1995).

    CAS  Google Scholar 

  70. 70.

    James, T. D., Linnane, P. & Shinkai, S. Fluorescent saccharide receptors: a sweet solution to the design, assembly and evaluation of boronic acid derived PET sensors. Chem. Commun. 1996, 281–288 (1996).

    Google Scholar 

  71. 71.

    Nöth, H. & Wrackmeyer, B. in Nuclear Magnetic Resonance Spectroscopy of Boron Compounds (eds Diehl, P., Fluck, E. & Kosfeld, R.) (NMR Basic Principles and Progress 14, Springer, 1978).

  72. 72.

    James, T. D. in Creative Chemical Sensor Systems 107–152 (Springer, 2007).

  73. 73.

    Silva, A. P. Recent evolution of luminescent photoinduced electron transfer sensors. A review. Analyst 121, 1759–1762 (1996).

    Google Scholar 

  74. 74.

    Bissell, R. A. et al. in Photoinduced Electron Transfer V 223–264 (Springer, 1993).

  75. 75.

    Beeson, J. C., Huston, M. E., Pollard, D. A., Venkatachalam, T. K. & Czarnik, A. W. Structural requirements for efficient photoinduced electron transfer (PET) quenching in 9-aminoalkylanthracenes. J. Fluoresc. 3, 65–68 (1993).

    CAS  PubMed  Google Scholar 

  76. 76.

    De Silva, A. P. et al. Signaling recognition events with fluorescent sensors and switches. Chem. Rev. 97, 1515–1566 (1997).

    PubMed  Google Scholar 

  77. 77.

    Lehn, J. M. Supramolecular chemistry—scope and perspectives molecules, supermolecules, and molecular devices (Nobel Lecture). Angew. Chem. Int. Ed. Engl. 27, 89–112 (1988).

    Google Scholar 

  78. 78.

    Matsumura, T., Iwatsuki, S. & Ishihara, K. Direct kinetic measurements for the fast interconversion process between trigonal boronic acid and tetragonal boronate ion at low temperatures. Inorg. Chem. Commun. 8, 713–716 (2005).

    CAS  Google Scholar 

  79. 79.

    Cooper, C. R. & James, T. D. Selective fluorescence signalling of saccharides in their furanose form. Chem. Lett. 27, 883–884 (1998).

    Google Scholar 

  80. 80.

    Chaberek, S., Courtney, R. C. & Martell, A. E. Stability of metal chelates. II. β-Hydroxyethyliminodiacetic acid. J. Am. Chem. Soc. 74, 5057–5060 (1952).

    CAS  Google Scholar 

  81. 81.

    Wiskur, S. L. et al. pK a values and geometries of secondary and tertiary amines complexed to boronic acids—implications for sensor design. Org. Lett. 3, 1311–1314 (2001).

    CAS  PubMed  Google Scholar 

  82. 82.

    Yoon, J. & Czarnik, A. W. Fluorescent chemosensors of carbohydrates. A means of chemically communicating the binding of polyols in water based on chelation-enhanced quenching. J. Am. Chem. Soc. 114, 5874–5875 (1992).

    CAS  Google Scholar 

  83. 83.

    Larkin, J. D., Fossey, J. S., James, T. D., Brooks, B. R. & Bock, C. W. A computational investigation of the nitrogen−boron interaction in o-(N,N-dialkylaminomethyl)arylboronate systems. J. Phys. Chem. A 114, 12531–12539 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84.

    Norrild, J. C. & Eggert, H. Boronic acids as fructose sensors. Structure determination of the complexes involved using 1 J CC coupling constants. J. Chem. Soc. Perkin Trans. 2 1996, 2583–2588 (1996).

    Google Scholar 

  85. 85.

    Kearns, F. L. et al. Modeling boronic acid based fluorescent saccharide sensors: computational investigation of d-fructose binding to dimethylaminomethylphenylboronic acid. J. Chem. Inf. Model. 59, 2150–2158 (2019).

    CAS  PubMed  Google Scholar 

  86. 86.

    Norrild, J. A fluorescent glucose sensor binding covalently to all five hydroxy groups of α-D-glucofuranose. A reinvestigation. J. Chem. Soc., Perk. Trans. 2 1999, 449–456 (1999).

    Google Scholar 

  87. 87.

    Collins, B. E., Metola, P. & Anslyn, E. V. On the rate of boronate ester formation in ortho-aminomethyl-functionalised phenyl boronic acids. Supramol. Chem. 25, 79–86 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. 88.

    Chandross, E. A. Photolytic dissociation of dianthracene. J. Chem. Phys. 43, 4175–4176 (1965).

    CAS  Google Scholar 

  89. 89.

    Chandross, E. A., Ferguson, J. & McRae, E. Absorption and emission spectra of anthracene dimers. J. Chem. Phys. 45, 3546–3553 (1966).

    CAS  Google Scholar 

  90. 90.

    McVey, J. K., Shold, D. M. & Yang, N. Direct observation and characterization of anthracene excimer in solution. J. Chem. Phys. 65, 3375–3376 (1976).

    CAS  Google Scholar 

  91. 91.

    Momiji, I., Yoza, C. & Matsui, K. Fluorescence spectra of 9-anthracenecarboxylic acid in heterogeneous environments. J. Phy. Chem. B 104, 1552–1555 (2000).

    CAS  Google Scholar 

  92. 92.

    Arimori, S., Bell, M. L., Oh, C. S., Frimat, K. A. & James, T. D. Modular fluorescence sensors for saccharides. J. Chem. Soc. Perkin Trans. 1 2001, 803–808 (2002).

    Google Scholar 

  93. 93.

    Camara, J. N., Suri, J. T., Cappuccio, F. E., Wessling, R. A. & Singaram, B. Boronic acid substituted viologen based optical sugar sensors: modulated quenching with viologen as a method for monosaccharide detection. Tetrahedron Lett. 43, 1139–1141 (2002).

    CAS  Google Scholar 

  94. 94.

    Arimori, S., Phillips, M. D. & James, T. D. Probing disaccharide selectivity with modular fluorescent sensors. Tetrahedron Lett. 45, 1539–1542 (2004).

    CAS  Google Scholar 

  95. 95.

    Phillips, M. & James, T. Boronic acid based modular fluorescent sensors for glucose. J. Fluoresc. 14, 549–559 (2004).

    CAS  PubMed  Google Scholar 

  96. 96.

    Xing, Z. et al. Selective saccharide recognition using modular diboronic acid fluorescent sensors. Eur. J. Org. Chem. 2012, 1223–1229 (2012).

    CAS  Google Scholar 

  97. 97.

    Sun, X. et al. A water-soluble boronate-based fluorescent probe for the selective detection of peroxynitrite and imaging in living cells. Chem. Sci. 5, 3368–3373 (2014).

    CAS  Google Scholar 

  98. 98.

    Dereka, B. & Vauthey, E. Direct local solvent probing by transient infrared spectroscopy reveals the mechanism of hydrogen-bond induced nonradiative deactivation. Chem. Sci. 8, 5057–5066 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. 99.

    Harris, C. M. & Selinger, B. K. Proton-induced fluorescence quenching of 2-naphthol. J. Phy. Chem. 84, 891–898 (1980).

    CAS  Google Scholar 

  100. 100.

    Sun, Z.-N., Liu, F.-Q., Chen, Y., Tam, P. K. H. & Yang, D. A highly specific BODIPY-based fluorescent probe for the detection of hypochlorous acid. Org. Lett. 10, 2171–2174 (2008).

    CAS  PubMed  Google Scholar 

  101. 101.

    Mirbach, M. J., Mirbach, M. F., Cherry, W. R., Turro, N. J. & Engel, P. Solvent isotope effect on the fluorescence of azoalkanes. Chem. Phys. Lett. 53, 266–269 (1978).

    CAS  Google Scholar 

  102. 102.

    Shizuka, H. & Tobita, S. Proton-induced quenching and hydrogen-deuterium isotope-exchange reactions of methoxynaphthalenes. J. Am. Chem. Soc. 104, 6919–6927 (1982).

    CAS  Google Scholar 

  103. 103.

    Lewis, G. N., Magel, T. T. & Lipkin, D. The absorption and re-emission of light by cis- and trans-stilbenes and the efficiency of their photochemical isomerization. J. Am. Chem. Soc. 62, 2973–2980 (1940).

    CAS  Google Scholar 

  104. 104.

    Kortüm, G. & Dreesen, G. Über die Konstitutionsabhängigkeit der Schwingungsstruktur im Absorptionsspektrum von aromatischen Kohlenwasserstoffen. Chem. Ber. 84, 182–203 (1951).

    Google Scholar 

  105. 105.

    Guesten, H., Mintas, M. & Klasinc, L. Deactivation of the fluorescent state of 9-tert-butylanthracene. 9-tert-butyl-9,10(Dewar anthracene). J. Am. Chem. Soc. 102, 7936–7937 (1980).

    CAS  Google Scholar 

  106. 106.

    Lewis, G. N. & Calvin, M. The color of organic substances. Chem. Rev. 25, 273–328 (1939).

    CAS  Google Scholar 

  107. 107.

    Hofer, L. J. E., Grabenstetter, R. J. & Wiig, E. O. The fluorescence of cyanine and related dyes in the monomeric state 1. J. Am. Chem. Soc. 72, 203–209 (1950).

    CAS  Google Scholar 

  108. 108.

    Rurack, K., Dekhtyar, M. L., Bricks, J. L., Resch-Genger, U. & Rettig, W. Quantum yield switching of fluorescence by selectively bridging single and double bonds in chalcones: involvement of two different types of conical intersections. J. Phy. Chem. A 103, 9626–9635 (1999).

    CAS  Google Scholar 

  109. 109.

    Ogunsipe, A., Chen, J.-Y. & Nyokong, T. Photophysical and photochemical studies of zinc(ii) phthalocyanine derivatives-effects of substituents and solvents. New J. Chem. 28, 822–827 (2004).

    CAS  Google Scholar 

  110. 110.

    DiCesare, N., Adhikari, D. P., Heynekamp, J. J., Heagy, M. D. & Lakowicz, J. R. Spectroscopic and photophysical characterization of fluorescent chemosensors for monosaccharides based on N-phenylboronic acid derivatives of 1,8-naphthalimide. J. Fluoresc. 12, 147–154 (2002).

    CAS  Google Scholar 

  111. 111.

    Collins, B. E. A Kinetic Investigation of Boronic Acid/Diol Interactions and Pattern-Based α-Chiral Carboxylate Recognition. PhD Thesis, Univ. Texas at Austin (2005).

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The authors gratefully acknowledge financial support for the several years of their work in the area of boronic acids. E.V.A. is grateful to the NSF (CHE-0716049, CHE-1212971), the Welch Foundation (F-1151) and the Welch Regents Chair (F-0046). B.W. acknowledges the Georgia Research Alliance, Georgia Cancer Coalition and the NIH throughout the years for their support of the boronic acid-relate projects (GM084933, CA159567, DK55062, CA88343, NO1-CO-27184, CA113917, CA123329 and GM086925). T.D.J. wishes to thank the Royal Society for a Wolfson Research Merit Award.

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Although the writing of the paper was spearheaded by E.V.A., the contents are a collaboration with T.D.J. and B.W.; X.S., B.M.C., P.M. and B.C. all contributed with experimental data and writing.

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Correspondence to Binghe Wang or Tony D. James or Eric V. Anslyn.

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Sun, X., Chapin, B.M., Metola, P. et al. The mechanisms of boronate ester formation and fluorescent turn-on in ortho-aminomethylphenylboronic acids. Nat. Chem. 11, 768–778 (2019).

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