A ‘turn-on’ fluorescent chemosensor for the detection of Zn2+ ion based on 2-(quinolin-2-yl)quinazolin-4(3H)-one

Xue-Jiao Bai; Jing Ren; Jia Zhou; Zhi-Bin Song

doi:10.1515/hc-2017-0136

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A ‘turn-on’ fluorescent chemosensor for the detection of Zn²⁺ ion based on 2-(quinolin-2-yl)quinazolin-4(3H)-one

Xue-Jiao Bai , Jing Ren , Jia Zhou and Zhi-Bin Song

Published/Copyright: May 28, 2018

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From the journal Heterocyclic Communications Volume 24 Issue 3

Abstract

2-(Quinolin-2-yl)quinazolin-4(3H)-one (Q) was synthesized via the Brønsted acid-promoted tandem cyclization/dehydrogenation reaction with a good yield. Compound Q is a selective ‘turn-on’ fluorescent sensor for Zn²⁺ ion without interference by Cd²⁺. The 1:1 binding model of Q to Zn²⁺ was confirmed by the Benesi-Hildebrand analysis, Job’s plot analysis and a ultraviolet-visible (UV-Vis) titration experiment. Furthermore, the light-on fluorescent response can be observed by the naked eye under UV-lamp irradiation (365 nm).

Keywords: fluorescent sensor; quinazolinone; Zn2+

Introduction

The detection of important metal ions using fluorescent chemosensors should be characterized by convenient application and rapid response [1], [2], [3]. Zinc ion is involved in many physiological processes such as immune and brain functions [4], [5]. In the human body, zinc ion is mostly complexed and free Zn²⁺ ion is scarce [6], [7]. It has been reported that free Zn²⁺ ion in the human body may cause serious diseases including Alzheimer’s disease [8], [9]. Therefore, the development of selective and sensitive fluorescent chemosensors for Zn²⁺ has attracted attention, and numerous fluorescence molecular structures have been designed for the sensing of Zn²⁺ by chelation [10], [11], [12], [13], [14], [15], [16]. Unfortunately, the existing sensors are difficult to synthesize and most of them are susceptible to interference from Cd²⁺ [10].

Quinazolinones are good candidates for fluorescent chemosensors in biological systems because of their remarkable biocompatibility [17], [18]. Recently, quinazolinone-based sensors for amine vapors [19] and Cu²⁺ ion [20] have been developed. We report that 2-(quinolin-2-yl)quinazolin-4(3H)-one (Q, Scheme 1) can be used as a simple and efficient ‘turn-on’ fluorescent chemosensor for a highly selective and sensitive detection of Zn²⁺.

Scheme 1

Synthesis of 2-(quinolin-2-yl)quinazolin-4(3H)-one (Q).

Results and discussion

Compound Q was synthesized by the treatment of o-aminobenzamide with quinoline-2-carboxaldehyde in the presence of [Ps₂TMEDA][HSO₄]₂ as a catalyst following the previously reported methodology (Scheme 1) [21]. This catalyst shows stronger acidity than common protic acids including H₂SO₄ and CH₃SO₃H.

The ultraviolet-visible (UV-Vis) absorption spectra of Q at various concentrations of Zn²⁺ in acetonitrile-water were recorded (Figure 1). The peaks at 306 nm, 326 nm, 336 nm and 355 nm are due to the UV absorption of quinoline and quinazoline systems of Q [22], [23]. The absorption is very weak in the range of 360–400 nm. With the addition of Zn²⁺, the absorption gradually increases in this range. Consequently, a wavelength of 375 nm was chosen for the excitation experiments.

Figure 1

(A) UV-Vis absorption spectra of Q (10⁻⁴m) and Q in the presence of five equivalents of Zn²⁺ ion. (B) UV-Vis absorption spectral changes during titration of Q (10⁻⁴m) with 0–2.5 equivalents of Zn²⁺; inset shows absorption as a function of Zn²⁺ ion concentration. All measurements were conducted in a mixture of CH₃CN and water (9:1) at room temperature.

Next, the fluorescence response of Q (10⁻⁵m) toward various metal ions including Cu²⁺, Ni²⁺, Co²⁺, Pb²⁺, Cs⁺, Ca²⁺, Cd²⁺, Ag⁺, Ba²⁺, Mg²⁺, Na⁺, Mn²⁺, Hg²⁺, Fe²⁺, Al³⁺, K⁺ and Zn²⁺ were examined (Figure 2A). As can be seen, the maximum emission peak of Q shows weak fluorescence at 425 nm. Compound Q (10⁻⁵m) also exhibits weak fluorescence at 473 nm with a quantum yield Ф_f<0.05 in a mixture of acetonitrile and water. After the addition of a metal ion including Ag⁺, Al³⁺, Ba²⁺, Ca²⁺, Co²⁺, Cr³⁺, Fe³⁺, K⁺, Mg²⁺ or Na⁺, the emission peak at 473 nm is increased to a small degree due to the weak coordination of Q with the metal. By contrast, the fluorescence intensity of Q (10⁻⁵m) at 473 nm is increased significantly in the presence of Zn²⁺ ion (one equivalent) with a quantum yield Ф_f of 0.43 (Figure 2A). The effects of anions were also tested. The results show that anions have almost no influence on the fluorescence intensity (Figure 2B). The remarkable change of the fluorescence color of Q (10⁻⁵m) from colorless to blue in the presence of Zn²⁺ (10⁻⁵m) upon irradiation with a UV lamp (365 nm) is shown in Figure 2C.

Figure 2

(A) Fluorescence intensity of Q (10⁻⁵m) in the presence of one equivalent of each of the following metal ions, Cu²⁺, Ni²⁺, Co²⁺, Pb²⁺, Cs⁺, Ca²⁺, Cd²⁺, Ag⁺, Ba²⁺, Mg²⁺, Na⁺, Mn²⁺, Hg²⁺, Fe²⁺, Al³⁺, K⁺ and Zn²⁺, upon excitation at 375 nm. (B) Fluorescence intensity of Q (10⁻⁵m) in the presence of one equivalent of various Zn²⁺ salts (Cl⁻, SO₄²⁻, CH₃COO⁻, NO₃⁻) upon excitation at 375 nm. (C) Visual fluorescence emission of sensor Q (10⁻⁵m) in the presence of Zn²⁺; note the lack of visible fluorescence in the presence of other metal ions (one equivalent each); the experiments were conducted in a mixture of acetonitrile and water (9:1) upon excitation at 365 nm using a UV lamp at room temperature.

In order to further investigate the selectivity of Q toward Zn²⁺, the competition assays were performed by measuring the fluorescence intensity of Q in the presence of Zn²⁺ and an additional metal ion. The results clearly demonstrated that the additional metal ion does not affect the strong fluorescence of Q in the presence of Zn²⁺ (not shown).

Finally, the fluorescence titration experiments were conducted to investigate the binding mode between Zn²⁺ and Q. With the increase in the concentration of Zn²⁺, the fluorescence intensity at 473 nm increases linearly (Figure 3). The 1:1 binding mode was confirmed using the Benesi-Hildebrand analysis (Figure 4) [24], [25], [26], Job’s plot analysis (Figure 5) [27], [28] and UV-Vis titration experiments (Figure 1B). The calculated detection limit (DL) of Zn²⁺ in the presence of Q is 8.82×10⁻⁷ mol L⁻¹, as calculated using the equation DL=3σ/B (Figure 6) [29], [30]. The binding constant (K_a) is 8.98×10⁴m⁻¹ using the equation K_a=B⁻¹×[F_max−F_min]⁻¹ [20].

Figure 3

Fluorescence titration of Q (5×10⁻⁶m), in CH₃CN/H₂O (9:1) upon excitation at 375 nm with successive addition of Zn²⁺ at room temperature. Inset shows fluorescence intensity as a function of Zn²⁺ ion concentration.

Figure 4

Benesi-Hildebrand plot (λ_em=473 nm) based on a 1:1 binding stoichiometry of Q with Zn²⁺.

Figure 5

Job’s plot for binding of Zn²⁺ to Q indicating the 1:1 binding ratio.

Figure 6

Normalized response of the fluorescence signal to change in Zn²⁺ concentration. The detection limit for Zn²⁺ is 8.82×10⁻⁷m.

Conclusions

A new ‘turn-on’ fluorescent chemosensor for the detection of Zn²⁺ ion based on 2-(quinolin-2-yl)quinazolin-4(3H)-one (Q) was synthesized. This compound shows a good sensitivity and selectivity for the recognition of Zn²⁺ even in the presence of many other metal ions including Cd²⁺ in a mixture of acetonitrile and water (9:1). The fluorescence quantum yield, Ф_f < 0.05, is dramatically increased to 0.43 in the presence of one equivalent of Zn²⁺ ion. This fluorescent change can be observed by the naked eye under UV-lamp irradiation at 365 nm.

Experimental

Nuclear magnetic resonance (NMR) spectra were recorded on a Bruker Avance 400 spectrometer. High resolution mass spectral (HRMS) analysis was performed using electrospray ionization-micro time-of-flight (ESI-microTOF). Solutions of Cu²⁺, Ni²⁺, Co²⁺, Pb²⁺, Cs⁺, Ca²⁺, Cd²⁺, Ag⁺, Mn²⁺, Na⁺, Mg²⁺, Fe²⁺, Al³⁺, Hg²⁺, Ba²⁺ and Zn²⁺ were generated from chloride salts using deionized water as a solvent. All spectral measurements were conducted at room temperature. Fluorescence spectra were measured on a Hitachi-F7000 fluorimeter. UV-Vis absorption spectra were measured on a Hitachi-UV3900 spectrophotometer. The width of excitation and emission slits was 5 nm. The fluorescence quantum yields (Ф_f) were measured on an Edinburgh-FLS980 spectrometer.

Synthesis of 2-(quinolin-2-yl)quinazolin-4(3H)-one (Q) [21]

A mixture of [Ps₂TMEDA][HSO₄]₂ (1 mmol, 555 mg), o-aminobenzamide (5 mmol, 681 mg) and 2-quinolinecarboxaldehyde (5 mmol, 786 mg) in ethanol (25 mL) was stirred at 80°C for 3 h, then cooled to room temperature and treated with a solution of sodium bicarbonate (20 mL). The resultant precipitate of Q was filtered, washed with deionized water (2×10 mL) and crystallized from ethanol/water: yield 79%, mp 264–226°C (lit. [31] mp 267–268°C); ¹H NMR (400 MHz, DMSO-d₆): δ 12.05 (s, 1H), 8.64 (d, J=8.8 Hz, 1H), 8.56 (d, J=8.8 Hz, 1H), 8.26 (m, 2H), 8.13 (m, 1H), 7.91 (m, 3H), 7.76 (m, 1H), 7.63 (m, 1H); ¹³C NMR (DMSO-d₆, 100 MHz): δ 161.4, 150.4, 149.0, 148.8, 146.8, 138.5, 135.3, 131.2, 129.8, 129.3, 128.9, 128.6, 128.3, 128.1, 126.7, 122.7, 119.1. ESI-HRMS. Calcd for C₁₇H₁₂N₃O, [M+H]⁺: m/z 274.0975. Found: m/z 274.0953

Acknowledgments

This work was supported by the Natural Science Foundations of Jiangxi Province, Funder Id: 10.13039/501100004479 (Grant No. 20161BAB213070) and Foundation of Key Laboratory of Functional Small Organic Molecules, Ministry of Education (KLFS-KF-201715).

References

[1] Sareen, D.; Kaur, P.; Singh, K. Strategies in detection of metal ions using dyes. Coord. Chem. Rev. 2014, 265, 125–154.10.1016/j.ccr.2014.01.015Search in Google Scholar

[2] Li, X.; Gao, X.; Shi, W.; Ma, H. Design strategies for water-soluble small molecular chromogenic and fluorogenic probes. Chem. Rev.2014, 114, 590–659.10.1021/cr300508pSearch in Google Scholar PubMed

[3] Kim, H. N.; Lee, M. H.; Kim, H. J.; Kim, J. S.; Yoon, J. A new trend in rhodamine-based chemosensors: application of spirolactam ring-opening to sensing ions. Chem. Soc. Rev.2008, 37, 1465–1472.10.1039/b802497aSearch in Google Scholar PubMed

[4] Frederickson, C.; Koh, J.; Bush, A. The neurobiology of zinc in health and disease. Nat. Rev. Neurosci.2005, 6, 449–462.10.1038/nrn1671Search in Google Scholar PubMed

[5] Bush, A.; Pettingell, W.; Multhaup, G.; Paradis, M.; Vonsattel, J.-P.; Gusella, J.; Beyreuther, K.; Masters, C.; Tanzi, R. Rapid induction of Alzheimer Aβ amyloid formation by zinc. Science1994, 265, 1464–1467.10.1126/science.8073293Search in Google Scholar PubMed

[6] Finney, L. A.; O’Halloran, T. V. Transition metal speciation in the cell: insights from the chemistry of metal ion receptors. Science2003, 300, 931–936.10.1126/science.1085049Search in Google Scholar PubMed

[7] Outten, C. E.; O’Halloran, T. V. Femtomolar sensitivity of metalloregulatory proteins controlling zinc homeostasis. Science2001, 292, 2488–2492.10.1126/science.1060331Search in Google Scholar PubMed

[8] Pedersen, J. T.; Hureau, C.; Hemmingsen, L.; Heegaard, N. H. H.; Østergaard, J.; Vašák, M.; Faller, P. Rapid exchange of metal between Zn₇–metallothionein-3 and amyloid-β peptide promotes amyloid-related structural changes. Biochemistry2012, 51, 1697–1706.10.1021/bi201774zSearch in Google Scholar PubMed

[9] Noy, D.; Solomonov, I.; Sinkevich, O.; Arad, T.; Kjaer, K.; Sagi, I. Zinc-Amyloid β interactions on a millisecond time-scale stabilize non-fibrillar Alzheimer-related species. J. Am. Chem. Soc.2008, 130, 1376–1383.10.1021/ja076282lSearch in Google Scholar PubMed

[10] Wu, Y.; Peng, X.; Guo, B.; Fan, J.; Zhang, Z.; Wang, J.; Cui, A.; Gao, Y. Boron dipyrromethene fluorophore based fluorescence sensor for the selective imaging of Zn in living cells. Org. Biomol. Chem. 2005, 3, 1387–1392.10.1039/b501795eSearch in Google Scholar PubMed

[11] Jung, J.; Dinescu, A. Emission pathway switching by solvent polarity: facile synthesis of benzofuran-bipyridine derivatives and turn-on fluorescence probe for zinc ions. Tetrahedron Lett.2017, 58, 358–361.10.1016/j.tetlet.2016.12.039Search in Google Scholar

[12] Ponnuvel, K.; Kumar, M.; Padmini, V. A new quinoline-based chemosensor for Zn²⁺ ions and their application in living cell imaging. Sensor Actuat. B Chem.2016, 227, 242–247.10.1016/j.snb.2015.12.017Search in Google Scholar

[13] Wei, X. D.; Wang, Q.; Tang, W. Q.; Zhao, S. L.; Xie, Y. S. Combination of pyrrole and pyridine for constructing selective and sensitive Zn²⁺ probes. Dyes Pigments2017, 140, 320–327.10.1016/j.dyepig.2017.01.064Search in Google Scholar

[14] Bumagina, N. A.; Antina, E. V.; Nikonova, A. Y.; Berezin, M. B.; Ksenofontov, A. A.; Vyugin, A. I. A new sensitive and selective off-on fluorescent Zn²⁺ chemosensor based on 3,3′,5,5′-tetraphenyl-substituted dipyrromethene. J. Fluoresc.2016, 26, 1967–1974.10.1007/s10895-016-1890-4Search in Google Scholar PubMed

[15] Li, H.; Zhang, S. J.; Gong, C. L.; Wang, J. Z.; Wang, F. A turn-on and reversible fluorescence sensor for zinc ion based on 4,5-diazafluorene Schiff base. J Fluoresc.2016, 26, 1555–1561.10.1007/s10895-016-1877-1Search in Google Scholar PubMed

[16] Findik, M.; Ucar, A.; Bingol, H.; Guler, E.; Ozcan, E. Fluorogenic ferrocenyl Schiff base for Zn²⁺ and Cd²⁺ detection. Res. Chem. Intermed.2017, 43, 401–412.10.1007/s11164-016-2630-8Search in Google Scholar

[17] Li, S.; Ma, J.-A. Core-structure-inspired asymmetric addition reactions: enantioselective synthesis of dihydrobenzoxazinone and dihydroquinazolinone based anti-HIV agents. Chem. Soc. Rev.2015, 44, 7439–7448.10.1039/C5CS00342CSearch in Google Scholar PubMed

[18] Kshirsagar, U. A. Recent developments in the chemistry of quinazolinone alkaloids. Org. Biomol. Chem.2015, 13, 9336–9352.10.1039/C5OB01379HSearch in Google Scholar PubMed

[19] Gao, M.; Li, S.-W.; Lin, Y.-H.; Geng, Y.; Ling, X.; Wang, L.-C.; Qin, A.-J.; Tang, B. Z. Fluorescent light-up detection of amine vapors based on aggregation-induced emission. ACS Sens. 2016, 1, 179–184.10.1021/acssensors.5b00182Search in Google Scholar

[20] Borase, P. N.; Thale, P. B.; Shankarling, G. S. Dihydroquinazolinone based “turn-off” fluorescence sensor for detection of Cu²⁺ ions. Dyes Pigments2016, 134, 276–284.10.1016/j.dyepig.2016.07.025Search in Google Scholar

[21] Yu, Z. Y.; Chen, M. Y.; He, J. X.; Tao, D. J.; Yuan, J. J.; Peng, Y. Y.; Song, Z. B. Controllable Brønsted acid-promoted aerobic oxidation via solvation-induced proton transfer: metal-free construction of quinazolinones and dihydroquinazolinones. Mol. Catal.2017, 434, 134–139.10.1016/j.mcat.2017.03.006Search in Google Scholar

[22] Crépin, C.; Dubois, V.; Goldfarb, F.; Chaput, F.; Boilot, J. P. A site-selective spectroscopy of naphthalene and quinoline in TEOS/MTEOS xerogels. Phys. Chem. Chem. Phys. 2005, 7, 1933–1938.10.1039/B500578GSearch in Google Scholar

[23] Chang, F.-R.; Wu, C.-C.; Hwang, T.-L.; Patnam, R.; Kuo, R.-Y.; Wang, W.-Y.; Lan, Y.-H.; Wu, Y.-C. Effect of active synthetic 2-substituted quinazolinones on anti-platelet aggregation and the inhibition of superoxide anion generation by neutrophiles. Arch. Pharm. Res.2003, 26, 511–515.10.1007/BF02976872Search in Google Scholar PubMed

[24] Benesi, H. A.; Hildebrand, J. H. A spectrophotometric investigation of the interaction of iodine with aromatic hydrocarbons. J. Am. Chem. Soc.1949, 71, 2703–2707.10.1021/ja01176a030Search in Google Scholar

[25] Tang, L. J.; Huang, Z. L.; Zheng, Z. X.; Zhong, K. L.; Bian, Y. J. A new thiosemicarbazone-based fluorescence “Turn-on” sensor for Zn²⁺ recognition with a large Stokes shift and its application in live cell imaging. J. Fluoresc.2016, 26, 1535–1540.10.1007/s10895-016-1827-ySearch in Google Scholar PubMed

[26] Jisha, V. S.; Thomas, A. J.; Ramaiah, D. Fluorescence ratiometric selective recognition of Cu²⁺ ions by dansyl-naphthalimide dyads. J. Org. Chem.2009, 74, 6667–6673.10.1021/jo901164wSearch in Google Scholar PubMed

[27] Dong, Z.; Le, X.; Zhou, P.; Dong, C.; Ma, J. Sequential recognition of zinc ion and hydrogen sulfide by a new quinoline derivative with logic gate behavior. New J. Chem.2014, 38, 1802–1808.10.1039/C3RA47755JSearch in Google Scholar

[28] Zhu, J. L.; Zhang, Y. H.; Chen, Y. H.; Sun, T. M.; Tang, Y. F.; Huang, Y.; Yang, Q. Q.; Ma, D. Y.; Wang, Y. P.; Wang, M. A Schiff base fluorescence probe for highly selective turn-on recognition of Zn²⁺. Tetrahedron Lett.2017, 58, 365–370.10.1016/j.tetlet.2016.12.041Search in Google Scholar

[29] Attia, M.; Youssef, A.; El-Sherif, R. Durable diagnosis of seminal vesicle and sexual gland diseases using the nano optical sensor thin film Sm-doxycycline complex. Anal. Chim. Acta2014, 835, 56–64.10.1016/j.aca.2014.05.016Search in Google Scholar PubMed

[30] Dimov, S. M.; Georgiev, N. I.; Asiri, A. M.; Bojinov, V. B. Synthesis and sensor activity of a PET-based 1,8-naphthalimide probe for Zn²⁺ and pH determination. J Fluoresc.2014, 24, 1621–1628.10.1007/s10895-014-1448-2Search in Google Scholar PubMed

[31] Lee, E. S.; Son, J. K.; Na, Y. H.; Jahng, Y. Synthesis and biological properties of selected 2-aryl-4(3H)-quinazolinones. Heterocycl. Commun.2004, 10, 325–330.10.1515/HC.2004.10.4-5.325Search in Google Scholar

Received: 2017-7-1

Accepted: 2018-3-6

Published Online: 2018-5-28

Published in Print: 2018-6-27

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https://doi.org/10.1515/hc-2017-0136

Keywords for this article

fluorescent sensor; quinazolinone; Zn2+

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