Detection of zinc (II) and hypochlorite by a thiourea-based chemosensor via two emission channels and its application in vivo

doi:10.1016/j.microc.2020.104788

Microchemical Journal

Volume 155, June 2020, 104788

https://doi.org/10.1016/j.microc.2020.104788 Get rights and content

Highlights

•
A new thiourea-based chemosensor THB was designed to simultaneous detection of zinc(Ⅱ) ion and ClO⁻.
•
THB could recognize zinc(Ⅱ) ion and ClO⁻ with low detection limits (0.67 μM for zinc(Ⅱ) ion and 0.28 μM for ClO⁻).
•
THB could successfully monitor both zinc(Ⅱ) ion and ClO⁻ in vivo.
•
THB was the first chemosensor capable of simultaneously monitoring zinc(Ⅱ) ion and ClO⁻ via two emission channels.
•
Response mechanisms of THB to zinc(Ⅱ) ion and ClO⁻ were supported by theoretical calculations.

Abstract

A novel thiourea-based chemosensor THB (N-benzhydryl-2-(thiophene-2-carbonyl)hydrazine-1-carbothioamide) was designed and investigated. THB had the capability to detect zinc ion and hypochlorite in a near-perfect aqueous media via different fluorescent emission channels. Limits of detection (LOD) were determined to be 0.67 µM for zinc ion and 0.28 µM for hypochlorite. Importantly, THB could successfully monitor both zinc ion and hypochlorite in zebrafish. Response mechanisms of THB to zinc ion and hypochlorite were demonstrated by ¹H NMR titrations, theoretical calculations, fluorescent and UV–vis spectral variations, and ESI-mass.

Introduction

The research on chemosensors for detecting diverse metal ions and anions has attracted much attention due to their wide applicability in biological, pathological, and industry environments [1,2]. Among the various metal ions, zinc ion is the second plentiful metal element in the human body and plays critical roles in metabolism including enzymatic reactions, brain functioning, DNA organization, and gene expression [3,4]. However, the disorder of zinc metabolism adversely affects brain functioning, blood cholesterol level, hair, and skin health [5], [6], [7] and also causes neurogenic diseases like Alzheimer's disease [8,9]. Thus, it is greatly significant to design chemosensors for monitoring zinc.

Hypochlorite, as a potential oxidant in ROS (reactive oxygen species), is generally produced from the peroxidation reaction between H₂O₂ and Cl⁻ in living organisms with the assistance of myeloperoxidase [10], [11], [12]. Hypochlorite plays critical roles in the immune defense of pathogen invasion [13,14]. However, the uncontrolled generation of hypochlorite may induce many problems such as neurodegenerative disorders and damage of tissue and organ [15,16]. In addition, water containing residual Cl⁻ adversely affects the blood circulation and nervous system [17,18]. Thus, it is of significant interest to study chemosensor for recognizing hypochlorite in water.

Among the various analytical tools, fluorometric analysis is a significantly preferred optical tool due to their high selectivity, sensitivity, fast response, and especially the capability of bioimaging [19], [20], [21]. To date, a number of fluorescence chemosensors for monitoring zinc or hypochlorite have been reported [22], [23], [24], [25], [26], [27], [28] and some of them have the capability to monitor the analytes in vitro and in vivo [29], [30], [31], [32], [33], [34], [35]. However, any fluorescent chemosensor detecting both zinc ion and hypochlorite has not been reported yet.

Thiourea has drawn much interest due to its diverse biological properties and ability as a recognition group toward various analytes [5,36,37]. Because the thiourea contains nitrogen, oxygen and sulfur atoms acting as electron-donor atoms, it has an excellent chelating capability to metal ions [38], [39], [40], [41] and could undergo oxidation reaction by ROS like ClO⁻ [42], [43], [44]. Therefore, we expected that a thiourea-based chemosensor could chelate metal ions and respond to ROS like hypochlorite by oxidation.

Herein, we developed a thiourea-based fluorescent chemosensor THB which could detect both zinc ion and hypochlorite. In addition, THB had a great capability to detect both zinc ion and hypochlorite in vivo. The response mechanisms of THB to zinc ion and hypochlorite were demonstrated, based on ¹H NMR titrations, theoretical calculations, fluorescent and UV–vis spectral variations, and ESI-mass.

Section snippets

General information

All reagents were provided commercially. ¹H NMR and ¹³C NMR were collected on a Varian spectrometer. Absorption and fluorescent spectra were collected on Perkin Elmer spectrometers. Quadrupole ion trap instrument was employed to get ESI-mass data. Agilent Cary 670 spectrometer was employed to obtain FT-IR spectra.

Synthesis of N-benzhydryl-2-(thiophene-2-carbonyl)hydrazine-1-carbothioamide (THB)

Thiophene-2-carbohydrazide (0.17 g, 1.2 × 10⁻³ mol) was dissolved in 6 mL of ethanol and benzhydryl isothiocyanate (0.23 g, 1.0 × 10⁻³ mol) was added into the solution. With stirring

Results and discussion

THB was produced from the nucleophilic addition reaction of thiophene-2-carbohydrazide and benzhydryl isothiocyanate (Scheme 1) and verified by ESI-mass, FT-IR, ¹H NMR and ¹³C NMR analysis (Fig. S1).

Conclusion

A new bifunctional fluorescent turn-on chemosensor THB was developed. THB could detect both zinc ion and hypochlorite for the first time, showing obvious fluorescence emissions. The detection limits of zinc ion and hypochlorite turned out to be 0.67 µM and 0.28 µM, which were lower than WHO protocols. In addition, THB showed the quantitative sensing ability for hypochlorite in real samples. Particularly, THB could be applied as a bioimaging fluorescent chemosensor for both Zn²⁺ and hypochlorite

CRediT authorship contribution statement

Haeri So: Investigation, Validation. Hanna Cho: Investigation, Validation. Hangyul Lee: Software, Formal analysis. Minh Cong Tran: Investigation, Validation. Ki-Tae Kim: Writing - review & editing, Supervision. Cheal Kim: Writing - review & editing, Supervision.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

This work was supported by Korea Environment Industry & Technology Institute (KEITI) through ``The Chemical Accident Prevention Technology Development Project", funded by Korea Ministry of Environment (MOE) (No. 2016001970001) and National Research Foundation of Korea (2018R1A2B6001686).

References (60)

D. Maity et al.
FRET-based rational strategy for ratiometric detection of Cu²⁺and live cell imaging
Sens. Actuators B.
(2013)
X.Q. Ma et al.
A novel AIE chemosensor based on quinoline functionalized pillar[5]arene for highly selective and sensitive sequential detection of toxic Hg²⁺ and CN⁻
Dyes Pigm.
(2019)
S.Y. Lee et al.
A dual chemosensor: colorimetric detection of Co²⁺ and fluorometric detection of Zn²⁺
J. Lumin.
(2016)
K. Jiang et al.
Concise synthesis of water soluble fluorescence sensor for sequential detection of Zn (II) and picric acid via cascade mechanism
Dyes Pigm.
(2019)
A. Pandith et al.
Highly selective imidazole-appended 9,10-N,N″-diaminomethylanthracene fluorescent probe for switch-on Zn²⁺ detection and switch-off H₂PO₄⁻ and CN⁻ detection in 80% aqueous DMSO, and applications to se
Sens. Actuators B.
(2017)
D. Liu et al.
1, 8-Naphthalimide-based fluorescent sensor with highly selective and sensitive detection of Zn²⁺ in aqueous solution and living cells
Inorg. Chem. Commun.
(2019)
V. Venkatesan et al.
Highly selective turn-on fluorogenic chemosensor for Zn²⁺ based on chelation enhanced fluorescence
Inorg. Chem. Commun.
(2019)
Y.M. Zhang et al.
Novel pillar[5]arene-based supramolecular organic framework gel for ultrasensitive response Fe³⁺ and F⁻ in water
Mater. Sci. Eng. C.
(2019)
F. Qin et al.
A mitochondrial-targeted fluorescent probe to sense pH and HOCl in living cells
Sens. Actuators B.
(2019)
D.Y. Lee et al.
A benzimidazole-based single molecular multianalyte fluorescent probe for the simultaneous analysis of Cu²⁺ and Fe³⁺
Tetrahedron Lett
(2010)

N. Narayanaswamy et al.

Reversible fluorescence sensing of Zn²⁺ based on pyridine-constrained bis(triazole-linked hydroxyquinoline) sensor

Supramol. Chem.

(2011)

P. Sun et al.

A coumarin Schiff's base two-photon fluorescent probe for hypochlorite in living cells and zebrafish

RSC Adv. 8

(2018)

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View full text

Detection of zinc (II) and hypochlorite by a thiourea-based chemosensor via two emission channels and its application in vivo

Highlights

Abstract

Introduction

Section snippets

General information

Synthesis of N-benzhydryl-2-(thiophene-2-carbonyl)hydrazine-1-carbothioamide (THB)

Results and discussion

Conclusion

CRediT authorship contribution statement

Declaration of Competing Interest

Acknowledgments

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Reversible fluorescence sensing of Zn²⁺ based on pyridine-constrained bis(triazole-linked hydroxyquinoline) sensor