3-Hydroxyphenylboronic Acid-Based Carbon Dot Sensors for Fructose Sensing

  • Diana M. A. Crista
  • Guilherme P. C. Mello
  • Olena Shevchuk
  • Ricardo M. S. Sendão
  • Eliana F. C. Simões
  • João M. M. Leitão
  • Luís Pinto da Silva
  • Joaquim C. G. Esteves da Silva


The selective fluorescence sensing of fructose was achieved by fluorescence quenching of the emission of hydrothermal-synthesized carbon quantum dots prepared by 3-hydroxyphenylboronic acid. Quantification of fructose was possible in aqueous solutions with pH of 9 (Limit of Detection LOD and Limit of Quantification LOQ of 2.04 and 6.12 mM), by quenching of the emission at 376 nm and excitation ~380 nm with a linearity range of 0–150 mM. A Stern-Volmer constant (KSV) of 2.11 × 10−2 mM−1 was obtained, while a fluorescent quantum yield of 31% was calculated. The sensitivity of this assay towards fructose was confirmed by comparison with other sugars (such as glucose, sucrose and lactose). Finally, the validity of the proposed assays was further demonstrated by performing recovery assays in different matrixes.

Graphical Abstract


Carbon dots Boronic acids Fructose Sensing Fluorescence quenching 



This work was made in the framework of the project Sustainable Advanced Materials (NORTE-01-00145-FEDER- 000028), funded by “Fundo Europeu de Desenvolvimento Regional (FEDER)”, through “Programa Operacional do Norte” (NORTE2020). Acknowledgment to project POCI- 01-0145-FEDER-006980, funded by FEDER through COMPETE2020, is also made. The Laboratory for Computational Modeling of Environmental Pollutants−Human Interactions (LACOMEPHI) is acknowledged. L.P. d.S. also acknowledges a post-doctoral grant funded by project Sustainable Advanced Materials (NORTE-01-00145-FEDER-000028). Projects PTDC/QEQ-QFI/0289/2014 and PTDC/QEQ-QAN/5955/ 2014 are also acknowledged. These projects are cofunded by FCT/MEC (PIDDAC) and by FEDER through “COMPETE− Programa Operacional Fatores de Competitividade” (COMPETE-POFC).


  1. 1.
    Johnson RJ, Nakagawa T, Sanchez-Lozada LG, Shafiu M, Sundaram S, Le M, Ishimoto T, Sautin YY, Lanaspa MA (2013) Sugar, uric acid, and the etiology of diabetes and obesity. Diabetes 62:3307–3315CrossRefGoogle Scholar
  2. 2.
    Khitan Z, Kim DH (2013) Fructose: a key factor in the development of metabolic syndrome and hypertension. J Nutr Metab 2013:12CrossRefGoogle Scholar
  3. 3.
    Nakagawa T, Tuttle KR, Short RA, Johnson RJ (2005) Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome. Nat Clin Pract Nephrol 1:80–85CrossRefGoogle Scholar
  4. 4.
    Bray GA, Nielsen SJ, Popkin BM (2004) Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 79:537–543CrossRefGoogle Scholar
  5. 5.
    Popkin BM, Adair LS, Ng SW (2012) Global nutrition transition and the pandemic of obesity in developing countries. Nutr Rev 70:3–21CrossRefGoogle Scholar
  6. 6.
    Hu FB, Malik VS (2010) Sugar-sweetened beverages and risk of obesity and type 2 diabetes: epidemiologic evidence. Physiol Behav 100:47–54CrossRefGoogle Scholar
  7. 7.
    Tappy L, Lê KA (2010) Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev 90:23–46CrossRefGoogle Scholar
  8. 8.
    Walker RW, Dumke KA, Goran MI (2014) Fructose content in popular beverages made with and without high-fructose corn syrup. Nutrition 30:928–935CrossRefGoogle Scholar
  9. 9.
    Kawasaki T, Akanuma H, Yamanouchi T (2002) Increased fructose concentrations in blood and urine in patients with diabetes. Diabetes Care 25:353–357CrossRefGoogle Scholar
  10. 10.
    Huang H, Yu H, Xu H, Ying Y (2008) Near infrared spectroscopy for on/in-line monitoring of quality in foods and beverages: a review. J Food Eng 87:303–313CrossRefGoogle Scholar
  11. 11.
    Wahjudi PN, Patterson ME, Lim S, Yee JK, Mao CS, Lee WN (2010) Measurement of glucose and fructose in clinical samples using gas chromatography/mass spectrometry. Clin Biochem 43:198–207CrossRefGoogle Scholar
  12. 12.
    Ma C, Sun Z, Chen C, Zhang L, Zhu S (2014) Simultaneous separation and determination of fructose sorbitol, glucose and sucrose in fruits by HPLC-ELSD. Food Chem 145:784–788CrossRefGoogle Scholar
  13. 13.
    Cataldi TRI, Margiotta G, Zambonin CG (1998) Determination of sugars and alditols in food samples by HPAEC with integrated pulsed amperometric detection using alkaline eluents containing barium or strontium ions. Food Chem 62:109–115CrossRefGoogle Scholar
  14. 14.
    Xiao Y, Li Y, Ying J, Tian Y, Xiao Y, Mei Z (2015) Determination of alditols by capillary electrophoresis with indirect laser-induced fluorescence detection. Food Chem 174:233–239CrossRefGoogle Scholar
  15. 15.
    Ilaslan K, Boyaci IH, Topcu A (2015) Rapid analysis of glucose, fructose and sucrose contents of commercial soft drinks using Raman spectroscopy. Food Control 48:56–61CrossRefGoogle Scholar
  16. 16.
    Alam AM, Kamruzzaman M, Dang TD, Lee SH, Kim YH, Kim GM (2012) Enzymeless determination of total sugar by luminol-tetrachloroaurate chemiluminescence on chip to analyze food samples. Anal Bioanal Chem 404:3165–3173CrossRefGoogle Scholar
  17. 17.
    Curey TE, Salazar MA, Oliveira P, Javier J, Dennis PJ, Rao P, Shear JB (2002) Enzyme-based sensor arrays for rapid characterization of complex disaccharide solutions. Anal Biochem 303:42–48CrossRefGoogle Scholar
  18. 18.
    Ashokkumar P, Bell J, Buurman M, Rurack K (2018) Analytical platform for sugar sensing in commercial beverages using a fluorescent BODIPY “light-up” probe. Sensors Actuators B Chem 256:609–615CrossRefGoogle Scholar
  19. 19.
    Kulmala S, Suomi J (2003) Current status of modern analytical luminescence methods. Anal Chim Acta 500:21–69CrossRefGoogle Scholar
  20. 20.
    Zhai J, Pan T, Zhu J, Xu Y, Chen J, Xie Y, Qin Y (2012) Boronic acid functionalized boron dipyrromethene fluorescent probes: preparation, characterization, and saccharides sensing applications. Anal Chem 84:10214–10220CrossRefGoogle Scholar
  21. 21.
    Wu X, Li Z, Chen XX, Fossey JS, James TD, Jiang YB (2013) Selective sensing of saccharides using simple boronic acids and their aggregates. Chem Soc Rev 42:8032–8048CrossRefGoogle Scholar
  22. 22.
    Chapin BM, Metola P, Vankayala SL, Woodcock HL, Mooibroek TJ, Lynch VM, Larkin JD, Anslyn EV (2017) Disaggregation is a mechanism for emission turn-on of ortho-Aminomethylphenylboronic acid-based saccharide sensors. J Am Chem Soc 139:5568–5578CrossRefGoogle Scholar
  23. 23.
    James TD, Sandanayake KRAS, Shinkai S (1996) Saccharide sensing with molecular receptors based on boronic acid. Angew Chem Int Ed Eng 35:1910–1922CrossRefGoogle Scholar
  24. 24.
    Hansen JS, Christensen JB, Petersen JF, Hoeg-Jensen T, Norrild JC (2012) Arylboronic acids: a diabetic eye on glucose sensing. Sensors Actuators B Chem 161:45–79CrossRefGoogle Scholar
  25. 25.
    Schiller A, Wessling RA, Singaram B (2007) A fluorescent sensor Array for saccharides based on Boronic acid appended Bipyridinium salts. Angew Chem Int Ed Eng 46:6457–6459CrossRefGoogle Scholar
  26. 26.
    Ramsay WJ, Bayley H (2018) Single-molecule determination of the isomers of D-glucose and D-fructose that bind to Boronic acids. Angew Chem Int Ed Eng 57:2841–2845CrossRefGoogle Scholar
  27. 27.
    Sun X, James TD, Anslyn EV (2018) 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 140:2348–2354CrossRefGoogle Scholar
  28. 28.
    Qian S, Liang Y, Ma J, Zhang Y, Zhao J, Peng W (2015) Simple boric acid-based fluorescent focusing for sensing of glucose and glycoprotein via multipath moving supramolecular boundary electrophoresis chip. Sensors Actuators B Chem 220:1217–1223CrossRefGoogle Scholar
  29. 29.
    James TD, Sandanayake KRAS, Shinkai S (1994) Novel photoinduced electron-transfer sensor for saccharides based on the interaction of boronic acid and amine. J Chem Soc Chem Commun:477–478Google Scholar
  30. 30.
    Lim S, Escobedo JO, Lowry M, Strongin RM (2011) Detecting specific saccharides via a single indicator. Chem Commun 47:8295–8297CrossRefGoogle Scholar
  31. 31.
    Elfeky SA, Flower SE, Masumoto N, D’Hooge F, Labarthe L, Chen WB, Len C, James TD, Fossey JS (2010) Diol appended quenchers for fluorescein Boronic acid. Chem Asian J 5:581–588CrossRefGoogle Scholar
  32. 32.
    Schiller A, Vilozny B, Wessling RA, Singaram B (2008) Recognition of phosphor sugars and nucleotides with an array of boronic acid appended bipyridinium salts. Anal Chim Acta 627:203–211CrossRefGoogle Scholar
  33. 33.
    Edwards NY, Sager TW, McDevitt JT, Anslyn EV (2007) Boronic-acid based Peptidic receptors for pattern-based saccharide sensing in neutral aqueous media, an application in real-life samples. J Am Chem Soc 129:13575–13583CrossRefGoogle Scholar
  34. 34.
    Zhou J, Zhou H, Tang J, Deng S, Yan F, Li W, Qu M (2017) Carbon dots doped with heteroatoms for fluorescent bioimaging: a review. Microchim Acta 184:343–368CrossRefGoogle Scholar
  35. 35.
    Baker SN, Baker GA (2010) Luminescent carbon nanodots: emergent nanolights. Angew Chem Int Ed 49:6726–6744CrossRefGoogle Scholar
  36. 36.
    Campos BB, Contreras-Cáceres R, Bandosz TJ, Jiménez-Jiménez J, Rodríguez-Castellón E, Esteves da Silva JCG, Algarra M (2017) Carbon dots coated with vitamin B12 as selective ratiometric nanosensor for phenolic carbofuran. Sensors Actuators B Chem 239:553–561CrossRefGoogle Scholar
  37. 37.
    Simões EFC, Leitão JMM, Esteves da Silva JCG (2017) Sulfur and nitrogen co-doped carbon dots sensors for nitric oxide fluorescence quantification. Anal Chim Acta 960:117–122CrossRefGoogle Scholar
  38. 38.
    Campos BB, Mutavdic D, Stankovic M, Radotic K, Lazaro-Martinez JM, Esteves da Silva JCG, Contreras-Cáceres R, Pino-Gonzalez MS, Rodriguez-Castellon E, Algarra M (2017) Thermo-responsive microgels based on encapsulated carbon quantum dots. New J Chem 41:4835–4832CrossRefGoogle Scholar
  39. 39.
    Campos BB, Abellan C, Zougagh M, Jimenez-Jimenez J, Rodriguez-Castellon E, Esteves da Silva JCG, Rios A, Algarra M (2015) Fluorescent chemosensor for pyridine based on N-doped carbon dots. J Colloid Interface Sci 458:209–216CrossRefGoogle Scholar
  40. 40.
    Simões EFC, Esteves da Silva JCG, Leitão JMM (2015) Peroxynitrite and nitric oxide fluorescence sensing by ethylenediamine doped carbon dots. Sensors Actuators B Chem 220:1043–1049CrossRefGoogle Scholar
  41. 41.
    Kirby EP, Steiner RF (1970) Influence of solvent and temperature upon the fluorescence of indole derivatives. J Phys Chem 74:4480–4490CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Diana M. A. Crista
    • 1
  • Guilherme P. C. Mello
    • 1
  • Olena Shevchuk
    • 1
  • Ricardo M. S. Sendão
    • 1
  • Eliana F. C. Simões
    • 2
  • João M. M. Leitão
    • 2
  • Luís Pinto da Silva
    • 1
    • 3
  • Joaquim C. G. Esteves da Silva
    • 1
    • 3
  1. 1.Chemistry Research Unit (CIQUP)Faculty of Sciences of University of PortoPortoPortugal
  2. 2.Chemistry Research Unit (CIQUP)Faculdade de Farmácia da Universidade de CoimbraCoimbraPortugal
  3. 3.LACOMEPHI, GreenUPortoFaculty of Sciences of University of PortoPortoPortugal

Personalised recommendations