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Selective non-enzymatic total bilirubin detection in serum using europium complexes with different β-diketone-derived ligands as luminescence probes

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Abstract

Three europium(III) complexes, Eu(ectfd)3 (Hectfd = 1-(9-ethyl-9H-carbazol-7-yl)-4,4,4-trifluorobutane-1,3-dione), Eu(tta)3 (Htta = 4,4,4-trifluoro-1-(thiophen-2-yl)-butane-1,3-dione), and Eu(dbt)3 (Hdbt = 2-(4',4',4'-trifluoro-1',3'-dioxobutyl)dibenzothiophene), were synthesized and employed to detect total bilirubin (BR) in blood-serum samples. UV-visible absorption and fluorescence (FL) spectroscopies were used to evaluate the selectivity of each europium (III) fluorescence probe to BR, which was shown to remarkably reduce the luminescence intensities of the europium(III) complexes at a wavelength of 612 nm. The luminescence intensity of each complex is linearly related to BR concentration. Eu(tta)3 was shown to be the more-appropriate fluorescence probe for the sensitive and reliable detection of total BR in blood serum samples than either Eu(ectfd)3 or Eu(dbt)3. This observation can be ascribed to special σ-hole bonding between Htta and BR. In addition, the optimal pH test conditions for the detection of BR in human serum by the Eu(tta)3 probe were determined. Sensitivity was shown to be dramatically affected by the pH of the medium. The experimental results reveal that pH 7.5 is optimal for this probe, which coincides with the pH of human serum. Furthermore, BR detection using the Eu(tta)3 luminescence probe is simple, practical, and relatively free of interference from coexisting substances; it has a minimum detection limit (DL) of 68 nM and is a potential candidate for the routine assessment of total BR in serum samples.

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References

  1. Pendse A, Jasani B, Nanavati R, Kabra N. Comparison of transcutaneous bilirubin measurement with total serum bilirubin levels in preterm neonates receiving phototherapy. Indian Pediatr. 2017;54(8):641–3.

    Article  PubMed  Google Scholar 

  2. I. Taurino, V. Van Hoof, A. Magrez, L. Forro, G. De Micheli, S. Carrara (2014) Efficient voltammetric discrimination of free bilirubin from uric acid and ascorbic acid by a CVD nanographite-based microelectrode. Talanta 130 (5):423–426

    Google Scholar 

  3. Balamurugan T, Berchmans S. Nonenzymatic detection of bilirubin based on a graphene–polystyrene sulfonate composite. RSC Adv. 2015;5(62):50470–7.

    Article  CAS  Google Scholar 

  4. Wang J, Wu X, Li Y, Han X, Hu H, Wang F, et al. Serum bilirubin concentrations and incident coronary heart disease risk among patients with type 2 diabetes: the Dongfeng-Tongji cohort. Acta Diabetol. 2017;54:257–2564.

    Article  CAS  PubMed  Google Scholar 

  5. Martelanc M, Ziberna L, Passamonti S, Franko M. Direct determination of free bilirubin in serum at sub-nanomolar levels. Anal Chim Acta. 2014;809:174–82.

    Article  CAS  PubMed  Google Scholar 

  6. Kannan P, Chen H, Lee VT, Kim DH. Highly sensitive amperometric detection of bilirubin using enzyme and gold nanoparticles on sol-gel film modified electrode. Talanta. 2011;86(86):400–7.

    Article  CAS  PubMed  Google Scholar 

  7. M. Martelanc, L. Ziberna, S. Passamonti, M. Franko (2016) Application of high-performance liquid chromatography combined with ultra-sensitive thermal lens spectrometric detection for simultaneous biliverdin and bilirubin assessment at trace levels in human serum. Talanta 154:92–98

    Google Scholar 

  8. Llorent-Martínez EJ, Durán GM, Ríos Á, Ruiz-Medina A. Graphene quantum dots-terbium ions as novel sensitive and selective time-resolved luminescent probes. Anal Bioanal Chem. 2017;410:1–418.

    Google Scholar 

  9. Vellaisamy K, Li G, Ko C-N, Zhong H-J, Fatima S, Kwan H-Y, et al. Cell imaging of dopamine receptor using agonist labeling iridium(III) complex. Chem Sci. 2017;9(5):1119–25.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hori Y, Otomura N, Nishida A, Nishiura M, Umeno M, Suetake I, et al. Synthetic-molecule/protein hybrid probe with fluorogenic switch for live-cell imaging of DNA methylation. J Am Chem Soc. 2018;140:1686–90.

    Article  CAS  PubMed  Google Scholar 

  11. Wang H, Feng Z, Sj DS, Rodal AA, Xu B. Active probes for imaging membrane dynamics of live cells with high spatial and temporal resolution over extended time scales and areas. J Am Chem Soc. 2018;140:3505–409.

    Article  CAS  PubMed  Google Scholar 

  12. Liu L-J, Wang W, Huang S-Y, Hong Y, Li G, Lin S, et al. Inhibition of the Ras/Raf interaction and repression of renal cancer xenografts in vivo by an enantiomeric iridium(III) metal-based compound. Chem Sci. 2017;8(7):4756–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wang W, Vellaisamy K, Li G, Wu C, Ko C-N, Leung C-H, et al. Development of a long-lived luminescence probe for visualizing β-galactosidase in ovarian carcinoma cells. Anal Chem. 2017;89(21):11679–84.

    Article  CAS  PubMed  Google Scholar 

  14. Liu JB, Yang C, Ko C-N, Vellaisamy K, Yang B, Lee M-Y, et al. A long lifetime iridium(III) complex as a sensitive luminescent probe for bisulfite detection in living zebrafish. Sensors Actuators B. 2016;243:971–6.

    Article  CAS  Google Scholar 

  15. Santhosh M, Chinnadayyala SR, Kakoti A, Goswami P. Selective and sensitive detection of free bilirubin in blood serum using human serum albumin stabilized gold nanoclusters as fluorometric and colorimetric probe. Biosens Bioelectron. 2014;59(5):370–6.

    Article  CAS  PubMed  Google Scholar 

  16. M. Santhosh, S.R. Chinnadayyala, N.K. Singh, P. Goswami (2016) Human serum albumin-stabilized gold nanoclusters act as an electron transfer bridge supporting specific electrocatalysis of bilirubin useful for biosensing applications. Bioelectrochemistry 111:7–14

    Google Scholar 

  17. Kamruzzaman M, Alam A-M, Lee SH, Kim YH, Kim G-M, Hyub S, et al. Spectrofluorimetric quantification of bilirubin using yttrium–norfloxacin complex as a fluorescence probe in serum samples. J Lumin. 2012;132(11):3053–7.

    Article  CAS  Google Scholar 

  18. Liang J, Xiong H, Wang W, Wen W, Zhang X, Wang S. Luminescent-off/on sensing mechanism of antibiotic-capped gold nanoclusters to phosphate-containing metabolites and its antibacterial characteristics. Sensors Actuators B. 2018;255:2170–8.

    Article  CAS  Google Scholar 

  19. Sasidharan A, Monteiro-Riviere NA. Biomedical applications of gold nanomaterials: opportunities and challenges. Wiley Interdiscip Rev: Nanomed Nanobiotechnol. 2015;7(6):779–96.

    CAS  Google Scholar 

  20. Reschgenger U, Gorris HH. Perspectives and challenges of photon-upconversion nanoparticles–Part I: routes to brighter particles and quantitative spectroscopic studies. Anal Bioanal Chem. 2017;409(25):5855–74.

    Article  CAS  Google Scholar 

  21. Wang M, Fang L, Li M, Liu Z, Hu Y, Zhang X. Effect of rare earth dopant onthermal stability and structure of ZnO-B2O3-SiO2. J Inorg Mater. 2017;32:643–8.

    Article  Google Scholar 

  22. Gorris HH, Resch-Genger U. Perspectives and challenges of photon-upconversion nanoparticles–Part II: bioanalytical applications. Anal Bioanal Chem. 2017;409(7):1–16.

    Google Scholar 

  23. Lourenco AV, Kodaira CA, Ramos-Sanchez EM, Felinto MC, Goto H, Gidlund M, et al. Luminescent material based on the Eu(TTA)3(H2O)2 complex incorporated into modified silica particles for biological applications. Inorg Chim Acta. 2013;123(6):11–7.

    CAS  Google Scholar 

  24. Zhang Y, Tang Y, Liu X, Zhang L, Lv Y. A highly sensitive upconverting phosphors-based off–on probe for the detection of glutathione. Sensors Actuators B. 2013;185(8):363–9.

    Article  CAS  Google Scholar 

  25. Eliseeva SV, Bunzli JC. Lanthanide luminescence for functional materials and bio-sciences. Chem Soc Rev. 2010;39(1):189–227.

    Article  CAS  PubMed  Google Scholar 

  26. Babailov SP. Thulium diketonate as NMR paramagnetic probe for moderately fast molecular dynamics and supersensitive reagent for in situ control of temperature. Sensors Actuators B. 2016;233:476–8.

    Article  CAS  Google Scholar 

  27. Yang W, Xia J, Zhou G, Jiang D, Li Q, Wang S, et al. Luminescent oxygen-sensing film based on β-diketone-modifiedEu(III)-doped yttrium oxide nanosheets. Sensors Actuators B. 2018;257:340–6.

    Article  CAS  Google Scholar 

  28. Liu SG, Pan RK, Zhou XP, Wen XL, Chen YZ, Wang S, et al. Blue-light exci europium(III) complex based on deprotonated1-(9-ethyl-6,8-dimethyl-9H-carbazol-2-yl) -4,4,4- trifluorobutane-1,3 -dionate and 1,10-phenanthroline. Inorg Chim Acta. 2013;395(2):119–23.

    Article  CAS  Google Scholar 

  29. R. W, Su Q. A study of intramolecular energy relaxation processes of rare earth complexes [Ln(TTA)3·2H2O, Ln = Nd, Eu, Gd]. J Mol Struct. 2000;559(1):195–9.

    Google Scholar 

  30. Parra DF, Forster PL, Łyszczek R, Ostasz A, Lugao AB, Rzączyńska Z. Thermal behavior of the highly luminescent poly(3-hydroxybutyrate):Eu(tta)3(H2O)2 red-emissive complex. J Therm Anal Calorim. 2013;114(3):1049–56.

    Article  CAS  Google Scholar 

  31. Faustino WM, Nunes LA, Terra IAA, Felinto MCFC, Brito HF, Malta OL. Measurement and model calculation of the temperature dependence of ligand-to-metal energy transfer rates in lanthanide complexes. J Lumin. 2013;137:269–73.

    Article  CAS  Google Scholar 

  32. Fernandes M, de Zea Bermudez V, Ferreira RAS, Carlos LD, Martins NV. Incorporation of the Eu(tta)3(H2O)2 complex into a co-condensed d-U(600)/d-U(900) matrix. J Lumin. 2008;128(2):205–12.

    Article  CAS  Google Scholar 

  33. Ellairaja S, Shenbagavalli K, Ponmariappan S, Vasantha VS. A green and facile approach for synthesizing imine to develop optical biosensor for wide range detection of bilirubin in human biofluids. Biosens Bioelectron. 2017;91(17):82–8.

    Article  CAS  PubMed  Google Scholar 

  34. Toietta G, Mane VP, Norona WS, Finegold MJ, Ng P, McDonagh AF, et al. Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helper-dependent adenoviral vector. Proc Natl Acad Sci U S A. 2005;102(11):3930–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nie Z, Fung YS. Microchip capillary electrophoresis for frontal analysis of free bilirubin and study of its interaction with human serum albumin. Electrophoresis. 2008;29(9):1924–31.

    Article  CAS  PubMed  Google Scholar 

  36. Zelenka J, Lenícek M, Muchová L, Jirsa M, Kudla M, Balaz P, et al. Highly sensitive method for quantitative determination of bilirubin in biological fluids and tissues. J Chromatogr B. 2008;867(1):37–42.

    Article  CAS  Google Scholar 

  37. Iwatani S, Nakamura H, Kurokawa D, Yamana K, Nishida K, Fukushima S, et al. Fluorescent protein-based detection of unconjugated bilirubin in newborn serum. Sci Rep. 2016;6:28489–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Luye M, Droujinine IA, Rajan NK, Sawtelle SD, Reed MA. Direct, rapid, and label-free detection of enzyme-substrate interactions in physiological buffers using CMOS-compatible nanoribbon sensors. Nano Lett. 2014;14(9):5315–22.

    Article  CAS  Google Scholar 

  39. Noh HB, Won MS, Shim YB. Selective nonenzymatic bilirubin detection in blood samples using a Nafion/Mn-Cu sensor. Biosens Bioelectron. 2014;61(1):554–61.

    Article  CAS  PubMed  Google Scholar 

  40. Ponhong K, Teshima N, Grudpan K, Vichapong J, Motomizu S, Sakai T. Successive determination of urinary bilirubin and creatinine employing simultaneous injection effective mixing flow analysis. Talanta. 2015;133:71–6.

    Article  CAS  PubMed  Google Scholar 

  41. Liu SG, Gong ML, Wang S, Tan XM. A luminescent Eu(III) complex based on 2-(4', 4', 4'-trifluoro-1', 3'-dioxobutyl)-dibenzothiophene for light-emitting diodes. Spectrochim Acta–Part A. 2009;74(3):731–4.

    Article  CAS  Google Scholar 

  42. Novotna P, Kralik F, Urbanova M. Chiral recognition of bilirubin and biliverdin in liposomes and micelles. Biophys Chem. 2015;205:41–50.

    Article  CAS  PubMed  Google Scholar 

  43. Kuenzle CC, Pelloni RR, Weibel MH. A proposed novel structure for the metal chelates of bilirubin. Biochem J. 1972;130(4):1147–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Zhuang QK, Dai HC, Liu H. Electrochemical study on the interaction of bilirubin with europium ions in aqueous media. Electroanalysis. 2015;11(18)):1368–71.

    Google Scholar 

  45. Millan S, Satish L, Kesh S, Chaudhary YS, Sahoo H. Interaction of lysozyme with rhodamine B: a combined analysis of spectroscopic and molecular docking. J Photochem Photobiol B. 2016;162:248–57.

    Article  CAS  PubMed  Google Scholar 

  46. Correa RS, Oliveira KM, Pérez H, Plutín AM, Ramos R, Mocelo R, et al. cis-bis(N-benzoyl-N′,N′-dibenzylthioureido)platinum(II): synthesis, molecular structure, and its interaction with human and bovine serum albumin. Arab J Chem. 2015; https://doi.org/10.1016/j.arabjc.2015.10.006.

  47. Roy AS, Ghosh P, Dasgupta S. Glycation of human serum albumin affects its binding affinity towards (−)-epigallocatechin gallate. Inclusion phenom. Macrocycl Chem. 2016;85(3/4):193–202.

    Google Scholar 

  48. Porter PS, Ward RC, Bell HF. The detection limit. Environ Sci Technol. 1988;22(8):856–61.

    Article  CAS  PubMed  Google Scholar 

  49. Murray JS, Lane P, Politzer P. Simultaneous σ-hole and hydrogen bonding by sulfur- and selenium-containing heterocycles. Int J Quantum Chem. 2008;108(15):2770–81.

    Article  CAS  Google Scholar 

  50. Iwaoka M, Isozumi N. Hypervalent nonbonded interactions of a divalent sulfur atom. Implications in protein architecture and the functions. Molecules. 2012;17(6):7266–83.

    Article  CAS  PubMed  Google Scholar 

  51. Lu J, Lu Y, Yang S, Zhu W. Theoretical and crystallographic data investigations of noncovalent S·O interactions. Struct Chem. 2011;22(4):757–63.

    Article  CAS  Google Scholar 

  52. Shishkin OV, Omelchenko IV, Kalyuzhny AL, Paponov BV. Intramolecular S···O chalcogen bond in thioindirubin. Struct Chem. 2010;21(5):1005–11.

    Article  CAS  Google Scholar 

  53. Politzer P, Murray JS, Clark T. Halogen bonding and other sigma-hole interactions: a perspective. Phys Chem Chem Phys. 2013;15(27):11178–89.

    Article  CAS  PubMed  Google Scholar 

  54. Gangan TVU, Sreenadh S, Reddy MLP. Visible-light exci highly luminescent molecular plastic materials derived from Eu3+ -biphenyl based β-diketonate ternary complex and poly(methylmethacrylate). J Photochem Photobiol A. 2016;328:171–81.

    Article  CAS  Google Scholar 

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Yang, W., Xia, J., Zhou, G. et al. Selective non-enzymatic total bilirubin detection in serum using europium complexes with different β-diketone-derived ligands as luminescence probes. Anal Bioanal Chem 410, 6459–6468 (2018). https://doi.org/10.1007/s00216-018-1243-z

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  • DOI: https://doi.org/10.1007/s00216-018-1243-z

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