Novel highly selective and sensitive fluorescent sensor for copper detection based on N-acylhydrazone acridone derivative

Article abstract of DOI:10.1016/j.molstruc.2019.126990

A new N-acylhydrazone based on acridone (S1) was synthesized by Schiff base condensation of 2-(9-oxoacridin-10-yl)acetohydrazide and salicylaldehyde and studied as selective fluorescence turn-off sensing towards Cu²⁺ ions in aqueous media. S1 demonstrated fluorescence turn-off sensing towards Cu²⁺ ions. Conversely, the metal ions K⁺, Mg²⁺, Zn²⁺, Fe²⁺, Al³⁺, Pb²⁺, Cr²⁺, Cd²⁺, Ag⁺, Fe³⁺, Ba²⁺, Hg²⁺, Mn²⁺, Co²⁺, and Ni²⁺ produced only minor decrease in the fluorescence of the system. The binding ratio of S1–Cu²⁺ complex was determined from the Job plot to be 1:2. Moreover, the S1–Cu²⁺ complex showed good fluorescence turn-off in presence of different counter ions of copper. In addition, the detection limit of S1 towards Cu²⁺ ions is 0.80 μM, which is enough for sensing the Cu²⁺ in the biological system and water within the U.S Environmental Protection Agency limit (～20 μM).

Full text of DOI:10.1016/j.molstruc.2019.126990

Journal Pre-proof
Novel highly selective and sensitive fluorescent sensor for copper detection based on
N-acylhydrazone acridone derivative
Mohammed Aarjane, Siham Slassi, Amina Amine
PII:
S0022-2860(19)31087-7
DOI:
https://doi.org/10.1016/j.molstruc.2019.126990
MOLSTR 126990
Reference:
To appear in: Journal of Molecular Structure
Received Date: 22 May 2019
Revised Date: 28 July 2019
Accepted Date: 26 August 2019
Please cite this article as: M. Aarjane, S. Slassi, A. Amine, Novel highly selective and sensitive
fluorescent sensor for copper detection based on N-acylhydrazone acridone derivative, Journal of
Molecular Structure (2019), doi: https://doi.org/10.1016/j.molstruc.2019.126990.
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Novel Highly Selective and Sensitive Fluorescent Sensor for
Copper Detection Based on N-acylhydrazone acridone Derivative.
Mohammed Aarjane, Siham Slassi, Amina Amine*
LCBAE, CMMBA, Faculty of Science, University Moulay Ismail, BP 11201 Zitoune,
Meknes, Morocco. *Corresponding author: e-mail: amine_7a@yahoo.fr
Abstract
A new N-acylhydrazone based on acridone (S1) was synthesized by Schiff base condensation of 2 (9
oxoacridin 10 yl)acetohydrazide and salicylaldehyde and studied as selective fluorescence turn-off sensing
towards Cu2+ ions in aqueous media. S1 demonstrated fluorescence turn-off sensing towards Cu2+ ions.
Conversely, the metal ions K+, Mg2+, Zn2+, Fe2+ , Al3+, Pb2+, Cr2+, Cd2+, Ag+, Fe3+, Ba2+, Hg2+, Mn2+, Co2+, and
Ni2+ produced only minor decrease in the fluorescence of the system. The binding ratio of S1–Cu2+ complex was
determined from the Job plot to be 1:2. Moreover, the S1-Cu2+ complex showed good fluorescence turn-off in
presence of different counter ions of copper. In addition, the detection limit of S1 towards Cu2+ ions is 0.80 µM,
which is enough for sensing the Cu2+ in the biological system and water within the U.S Environmental Protection
Agency limit (~ 20 µM).
Keywords: Acridone, Acylhydrazone, Copper ion, Fluorescent chemosensor, Quenching.
1

1. Introduction
Molecular chemosensing is a promising research field in chemistry with established roles in ecological and
biological areas. [1]. Metal ions recognition is one of the interesting applications of these kind of molecules
especially for fluorescent chemosensors that show some advantages due to their rapid responses, high selectivity
and high sensitivity [2–9]. Thus, it has always been interesting to develop new fluorescent probes for such
potential applications. As one of the crucial trace elements for biological systems, copper participates to
important biochemical processes including antioxidative defense, energy metabolism and iron metabolism [10-
16]. However, any increase in copper concentration can lead to many neurologic diseases [10]. Moreover,
copper, among other metals, is considered as a substantial pollutant and its upper limit in drinking water was set
to 1.3 ppm [18]. These facts bring out clearly the important impact of developing new chemosensors for
effective and quantitative copper ion recognition in biology, chemistry, environmental science, and medicine
[19–21]. Most of the reported probes exhibit a turn-on fluorescence response but only few ones are known as
turn-off fluorescent probes [22–24].
Acridone and its derivatives are a promising class of heterocycles, which were at first used as stains, and that
have received a great attention for their diverse pharmaceutical applications such as antitumor agents, antivirals,
antimalarials, and antibacterials [25–29]. Additionally, due to their interesting optical properties and excellent
photostability, acridones are used as dyes, fluorescent materials for visualization of biomolecules and in laser
technologies [30] but, apparently, there are only few reports on acridone derivatives fluorescent probes for metal
ions detection.
In this study, we report the synthesis of a novel chemosensor (S1) for Cu2+ recognition which was obtained by a
condensation reaction of 2‐(9‐oxoacridin‐10‐yl)acetohydrazide and salicylaldehyde. The compound was
designed as a combination of an acridone ring that constitute the fluorophore unit and a coordination unit formed
by a salicyl moiety and an acylhydrazone unit. This later is known to be a good coordinating site for various
metal cations due to both the imine nitrogen atom and the amide oxygen atom [31-33]. The sensor S1 can detect
Cu2+ by a significant fluorescence turn-off response in the presence of Cu2+ ions in aqueous media.
2. Experimental
2.1 Materials
All materials were purchased from commercial suppliers. Infrared spectra were recorded using a JASCO FT-IR
4100 spectrometer. Fluorescence measurements were realized on a SHIMADZU RF-1501 spectrofluorometer.
2

1
UV-visible absorption spectra were recorded on a SHIMADZU UV-1800 spectrophotometer. The H and 13C
NMR spectra were recorded with a Bruker Avance 300 at 25°C. Mass spectrometric measurements were
recorded using SHIMADZU 8040 LC/MS/MS. The metal ion solutions were prepared from KCl, MgCl2,
NiCl2.6H2O, ZnCl2, FeCl2, AlCl3.6H2O, PbCl2, CrCl2, CdCl2.5H2O, AgCl, FeCl3, BaCl2, HgCl2, MnCl2, CoCl2,
CuCl2, Cu(CF₃SO₃)₂, Cu (NO3)2.6H2O, CuSO4.6H2O, Cu(CO2CH3)2. H2O and Cu(ClO4)2.
2.2 Synthesis
2.2.1 Synthesis of acridone from 2-(phenylamino)benzoic acid (2)
A mixture of aniline (0.65 g, 7 mmol), o-bromobenzoic acid (1 g, 5 mmol), anhydrous potassium carbonate (0.82
g, 6 mmol), 0.1 g of metallic copper powder and 0.04 g of copper oxide was refluxed for 4h in 15 ml of amyl
alcohol. The amyl alcohol was evaporated then poured into (100 ml) hot water, cooled to room temperature. The
medium pH was then adjusted to 4 by adding HCl (0.5 M). Compound 1 was obtained as a white precipitate
which was then recrystallized from ethanol. The N-phenylantranilic acid (1g, 4.7 mmol) was taken in 4 ml of
concentrated sulfuric acid and heated on water bath for 3 h. Reaction mixture was added to hot water and the
resulting precipitates were filtered to get acridone. The sample of acridone 2 was recrystallized from acetic acid.
1
Yield 70%, m.p. > 330 C. IR (KBr, cm-1) 3275 (N– H), 3084 (C–H aromatic), 1640 (C=O), 1570 (C=C). H
NMR (DMSO d6) δ (ppm): 11.74 (s, 1H, NH), 8.23 (dd, J = 8.1, 1.2 Hz, 2H, H1-H8), 7.70 (td, J = 8.4, 1.5 Hz,
2H, H3-H6), 7.53 (d, J= 8.1 Hz, 2H, H4-H5), 7.23 (td, J = 8.4, 1.5 Hz, 2H, H2-H7). 13C NMR (300 MHz, DMSO-
d6) δ (ppm): 177.29 (C=O), 141.35 (C4a-C10a), 133.94 (C3-C6), 126.46 (C1-C8), 121.49 (C4-C5), 120.91 (C8a-C9a),
117.80 (C2-C7).
2.2.2 2 (9 oxo 9,10 dihydroacridin 10 yl)acetohydrazide (3)
To a mixture of acridone 2 (0.5g, 2.5 mmol) and sodium hydride (45 mg, 3.6 mmol) in DMF (3 ml), ethyl 2-
bromoacetate (0.6g, 3.6 mmol) was added dropwise. The mixture was stirred at 60°C for 3h then poured into
crushed ice. The ester precipitated as a white yellow solid, it was recrystallized from ethanol-DMF. Hydrazine
monohydrate (5mL) was added to a 2 mL solution of the ester (0.56g, 2 mmol) in DMSO and the mixture was
refluxed for 24 h. Compound 3 was obtained as a solid after solvent evaporation and it was purified by
recrystallization from DMF-ethanol.
Yield: 80%; yellow solid; m.p> 300°C; IR (KBr, cm-1) 3320 (N-H), 3084 (C–H aromatic), 1670, 1640 (C=O),
1570 (C=C); 1H NMR (300 MHz, DMSO-d6,) δ (ppm): 9.55 (s, 1H, NH), 8.34 (dd, J 8.1 Hz, 1.5 Hz, 2H), 7.80
(m, 2H, H3-H6), 7.62 (d, J= 8.1Hz, 2H, H4-H5 ), 7.34 (td, 2H, J = 8.4, 1.5 Hz, 2H, H2-H7 ), 5.13 (s, 2H, CH2),
3

4.35 (s, 2H, NH2). 13C NMR (300 MHz, DMSO-d6) δ (ppm): 177.23, 167.00, 142.98, 134.45, 126.98, 122.15,
121.89, 116.42, and 47.98.
2.2.3 N' [ (2 hydroxyphenyl)methylidene] 2 (9 oxo 9,10 dihydroacridin 10 yl)acetohydrazide (S1)
An equimolar mixture of 2-(9-oxoacridin-10(9H)-yl) acetohydrazide 3 (0.26g, 1mmol) and salicylaldehyde (0.1
g, 1mmol) was refluxed in ethanol for 4 h. The reaction mixture was filtered and the obtained solid was dried
then recrystallized from a mixture of DMF and ethanol.
Yield: 80%; White solid; m.p> 300°C. IR (KBr, cm-1) 3300, 3084, 2967, 1680, 1635, 1602 1480. 1H NMR (300
MHz, DMSO-d6,) δ (ppm): 11.84 (s, 1H, NH), 10.08 (s, 1H, OH), 8.45 (s, 1H, N=CH), 8.36 (d, 2H, J= 8.1Hz,
Ar-H), 7.86-7.54 (m, 5H, Ar-H), 7.34-7.27 (m, 3H, Ar-H), 7.25-6.84 (m, 2H, Ar-H), 5.71 (s, 2H, N-CH2). 13C
NMR (300 MHz, DMSO-d6) δ (ppm): 177.26, 168.65, 156.96, 148.10, 142.99, 142.92, 134.66, 134.47, 131.87,
129.53, 127.61, 127.00, 122.14, 122.05, 121.88, 120.64, 119.10, 116.39, and 47.67. MS(ESI)m/z: 372.13 [M+1]
+
.
2.3 UV-visible and fluorescence studies
The UV-Visible absorption and fluorescence spectra of the compound in DMSO–H2O (4:1, v/v) were recorded
on SHIMADZU UV-1800 spectrophotometer and SHIMADZU RF-1501 spectrofluorometer, respectively. The
Cu2+ solution was prepared by dissolving copper salts in distilled water and DMSO. The probes stock solutions
were prepared in DMSO–H2O (4:1, v/v). Aqueous metal ions solutions were also prepared using distilled water
and DMSO. For the fluorescence measurements, the excitation wavelength was fixed at 320 nm; the emission
wavelengths were scanned from 330 nm to 600 nm with 1 nm increments.
The quantum yield of sensor S1 was determined according to the following equation :
ФS/ФR= (FS/FR)*(AS/AR)*(ηS/ηR)2.
where ФS and ФR are the fluorescence quantum yields of the sample and the reference respectively; F is the
integrated area under the corrected emission spectra; A is the absorbance at the excitation wavelength; η is the
refractive index of the solution. Quinine sulfate in 0.1 M H2SO4 solution was used as the standard [34].
3. Results and discussion
3.1 Synthesis
The synthetic route to the novel N-acylhydrazone acridone, as depicted in Scheme 1, was started from Ullmann
condensation of 2- bromobenzoic acid and aniline in presence of a base and copper in isoamyl alcohol to give 2-
4

arylamino benzoic acids. The obtained product was cyclized in sulphuric acid at 100 °C to give acridone [35].
The acridone was reacted with ethyl 2-bromoacetate using sodium hydride in DMF at 70 °C, followed by
nucleophilic substitution of this intermediate with hydrazine in DMSO. N-acylhydrazone acridone was obtained
in the last step by an acid catalyzed condensation of 9-oxo-9,10-dihydroacridine-4-carboxylic acid hydrazide
with salicylaldehyde for 2 h in ethanol to give the corresponding product in good yield 80%.
1
The structure of S1 was elucidated using FT-IR, H NMR, 13C NMR and MS analysis. The FT-IR spectrum of
compound (S1) showed characteristic absorption bands at 1680 cm-1 due to the presence of the amide group and
at 1635 cm-1 corresponding to the carbonyl of the acridone ring. The characteristic band of the imine moiety was
detected at 1602 cm-1. OH and NH stretching bands appeared as a broad band at 3300 cm-1. 1H NMR spectrum of
compound (S1) showed a singlet at δH 8.45 ppm attributable to the proton of the imine and signals at the
aromatic region δH 8.36–7.23 ppm relative to the aromatic protons. In addition, the compound (S1) showed two
signals at δH 11.84 and 10.08 ppm corresponding to NH and OH groups respectively. These structures were
further supported by 13C and DEPT NMR spectra, which showed all the expected carbon signals, essentially the
carbon of imine group resonating at δC 156.9 ppm and the signal of the amide moiety resonated at δC 168.6 ppm.
The characteristic signal of the carbonyl on the acridone ring resonated at 177.2 ppm.
Scheme 1 Synthetic pathway to compound S1. Reagent and reaction conditions: (a) K2CO3, cat. Cu/CuO, reflux;
(b) H2SO4, 80 °C (c) ethyl 2-bromoacetate, NaH, DMF, N2H4.H2O, DMSO, reflux; (d) salicylaldehyde, ethanol,
reflux
3.2 Absorbance and Fluorescence Spectra.
3.2.1 UV–vis spectroscopic studies
The UV–vis spectra of S1 show absorption bands at 273 nm, 325 nm, 379 nm and 398 nm respectively (Fig. 1a).
The gradual adding of Cu2+ ions in increasing concentration (0-30µM), led to significant enhancement in the
5

absorption intensity of the bands at 273 nm, 379 nm and 398 nm, while the band at 325 nm showed significant
decrease. The appearance of tow isosbestic points centered at λ = 319 and 343 nm for S1-Cu2+ is consistent with
an equilibrium between S1 and S1-Cu2+ complex in solution. The Job’s plot (Fig. 1b) indicates that the formation
of complex S1-Cu2+ is the 1:2 stoichiometry signifying the formation of a ML2 complex. Potential sites of
copper coordination might likely be the hydroxy group and the imine nitrogen atom of the hydrazine unit that is
known to be a good coordinating site for various metal cations. The experiment was carried out with other metal
cations (K+, Mg2+, Zn2+, Fe2+, Al3+, Pb2+, Cr2+, Cd2+, Ag+, Fe3+, Ba2+, Hg2+, Mn2+, Co2+, and Ni2+) and we have
noticed that the addition of these metal cations did not alter significantly the initial absorption spectrum of
chemosensor S1.
Fig. 1 a) The absorption spectrum of S1 (10 ꢀM) in the presence of increasing concentration (0-30 ꢀM) of Cu2+.
b) Job’s plot for determination of the stoichiometry of S1-Cu2+ at 330 nm
3.2.2 Fluorescence spectral studies
The sensitivity and selectivity of our newly synthesized compound S1 towads different metal ions were
performed by studying the fluorescence spectra changes upon addition of chloride salts of a wide range of
cations in DMSO–H2O (4:1, v/v) solution, including: K+, Mg2+, Cu2+, Zn2+, Fe2+, Al3+, Pb2+, Cr2+, Cd2+, Ag+,
Fe3+, Ba2+, Hg2+, Mn2+, Co2+, and Ni2+. The fluorescence spectrum of S1, which was excited at 320 nm, exhibited
the emission maximum at 410 nm with a high fluorescence intensity. The quantum yield of sensor S1 was
determined using quinine sulfate in 0.1 M H2SO4 solution as the standard (Φ=0.54). The quantum yield of S1
and S1-Cu2+ are 0.43 and 0.008 respectively. The decrease of fluorescence upon Cu2+ binding could be due to a
photoinduced electron transfert (PET): a process that involves the donation of an electron from the fluorophore
to the metal cation Cu2+ which is well known as a strong quencher. [36].
6

Selectivity is an important parameter to estimate the performance of a new fluorescent probe. Therefore, the
selective performance of chemosensor S1 was estimated by studying the response of S1 towards the studied
metallic cations: K+, Mg2+, Cu2+, Zn2+, Fe2+, Al3+, Pb2+, Cr2+, Cd2+, Ag+, Fe3+, Ba2+, Hg2+, Mn2+, Co2+, and Ni2+.
The excitation wavelength selected for S1 was 320 nm. As shown in (Fig. 2), an important fluorescence turn-off
was observed upon the addition of Cu2+ ions, the quantum yield ΦS1 of the chemosensor decreased from 0.43 to
0.008. Meanwhile the interaction of the other mentioned ions with S1 showed non-noticeable changes in the
fluorescence intensity except for Fe2+ ions for which a small decrease in the fluorescent emission intensity was
observed.
To explore the possibility of using S1 as a practical ion-selective fluorescent probe for Cu2+, competition
experiments were carried out in the presence of 3 equiv. of various metal ions such as K+, Mg2+, Zn2+, Fe2+, Al3+,
Pb2+, Cr2+, Cd2+, Ag+, Fe3+, Ba2+, Hg2+, Mn2+, Co2+, and Ni2+. The fluorescence intensity of S1 showed very little
fluorescence intensity changes, after addition 2 equiv. of Cu2+ ions a clear fluorescence turn-off was observed in
all solutions (Fig. 3). All these results clearly reveal that probe S1 displayed specific selectivity towards Cu2+
with no interference with other competing ions. This Cu2+-sensitive fluorescence quenching behavior suggests
that S1 can be used as a selective sensing probe for the analysis of Cu2+ ions.
Fig. 2 Fluorescence spectra of S1 (1µM) with 3 equiv of different ions: K+, Mg2+, Cu2+, Zn2+, Fe2+, Al3+, Pb2+,
Cr2+, Cd2+, Ag+, Fe3+, Ba2+, Hg2+, Mn2+, Co2+, and Ni2+ (1 mM) in DMSO–H2O (4:1, v/v), λex = 320 nm
7

Fig.3 Selectivity of S1 for Cu2+ in the presence of other metal ions in DMSO–H2O (4:1, v/v). Blue bars represent
the addition of 3 equiv of the appropriate metal ion: K+, Mg2+, Cu2+, Zn2+, Fe2+, Al3+, Pb2+, Cr2+, Cd2+, Ag+, Fe3+,
Ba2+, Hg2+, Mn2+, Co2+, and Ni2+ to a 1 ꢀM solution of S1. Orange bars represent the subsequent addition of 3
equiv of Cu2+to the solution
In the fluorescence titrations of S1 with Cu2+ ions, the concentration of Cu2+ was gradually varied from 0 to 3
µM. The emission of S1 was measured after the addition of the copper ions to the solution of S1 in DMSO-H2O
(4:1). The fluorescence intensity of S1 at 410 nm was quenched gradually while increasing the concentrations of
Cu2+ ions, the addition of 3 equivalents of Cu2+ showed significant quenching in the fluorescence of the
chemosensor S1 (Fig. 4).
Fig.4 Fluorescence titration of probe S1 (1 µM) with Cu2+ in DMSO–H2O (4:1, v/v), λex = 320 nm
8

The quenching efficiency of the Cu2+ ions was analyzed using the Stern-Volmer relation [37] (1).
I0/I = 1 + Ksv [Q]
(1)
Where I0 and I are the fluorescence intensities of S1 in the absence and presence of Cu2+ ions, respectively, Ksv
is the Stern–Volmer quenching constant and [Q] is the concentration of the Cu2+ ions. The mechanisms of
quenching are generally static quenching, dynamic quenching, or combined dynamic and static quenching [38,
39]. The static quenching mechanism is observed when a complex fluorophore-metal is formed. This complex
formation leads frequently to a change in the absorption spectrum. Conversely, dynamic quenching affects only
the excited states of the fluorophore and consequently does not induce any change in the absorption spectrum
[40]. In the absorbance spectra of S1, a change is clearly seen in the presence of copper ions as a quencher (Fig.
1) which shows that the mechanism of fluorescence quenching involves static quenching. Similar quenching
mechanism was reported for various protein-drug [41], protein-herbicide [42] and protein-flavonoid [43]. The
quenching is measured with Stern–Volmer equation. The calculated Stern–Volmer constant Ksv of S1 with
copper is 1.25 106 M-1. The limit of detection was determined from the decreased fluorescence intensity at 410
nm of S1 and calculated by 3σ/S, where σ represents the standard deviation of the blank solution, and S is the
slope of the calibration curve. The limit of detection was 0.8 µM, which is enough for sensing the Cu2+ in the
biological system and water within the U.S. EPA limit (~ 20 µM) [18].
Fig.5 Stern–Volmer plot of fluorescence intensity ratios (I0/I) versus Cu2+ concentrations
9

In order to further elucidate if the fluorescence of the S1-Cu2+ complex was affected by the presence of counter
ions in DMSO-H2O medium, we performed the sensor S1 (1 µM) titrations with Cu2+ (3 µM) using different
counter ion salts. As evidenced in Fig. 6, the Cu2+ sensor response was found to be decreased whatever was the
-
2-
-
counter ions: TfO-, NO3 , Cl-, SO4 , CH3COO- or ClO4 . The best quenching was detected in the presence of
copper perchlorate and copper chloride, whereas the slightest response was provided in presence of copper
triflate. We can also conclude that the sensing selectivity of S1 towards Cu2+ was incredibly not affected by the
nature of the counter ion.
Fig.6 Sensor responses of S1 (1 µM) in DMSO-H2O towards Cu2+ in presence of different counter ions Cu2+:
-
2-
-
TfO-, NO3 , Cl-, SO4 , CH3COO- and ClO4
4. Conclusion
In conclusion, a novel N-acylhydrazone derived from acridone S1 has been easily synthesized for selective
sensing of copper ions in aqueous media. The high sensitivity and selectivity towards copper ions was
demonstrated from the fluorescence titration. Efficient fluorescence quenching was also demonstrated in
presence of diffetent counter ions of copper. Additionally, the quenching mechanism of S1 was examined from
the corresponding Stern–Volmer plots. And the limit of detection (0.8µM) is sufficient for sensing the Cu2+ in
the biological system and water.
References
[1]
E.L. Que, D.W. Domaille, C.J. Chang, Metals in Neurobiology: Probing Their Chemistry and Biology
with Molecular Imaging, Chem. Rev. 108 (2008) 1517–1549. doi:10.1021/cr078203u.
10

[2]
[3]
[4]
[5]
[6]
M. Formica, V. Fusi, L. Giorgi, M. Micheloni, New fluorescent chemosensors for metal ions in solution,
Coord. Chem. Rev. 256 (2012) 170–192. doi:10.1016/J.CCR.2011.09.010.
C.R. Lohani, K.-H. Lee, The effect of absorbance of Fe3+ on the detection of Fe3+ by fluorescent
chemical sensors, Sensors Actuators B Chem. 143 (2010) 649–654. doi:10.1016/J.SNB.2009.10.004.
J.S. Kim, D.T. Quang, Calixarene-Derived Fluorescent Probes, Chem. Rev. 107 (2007) 3780–3799.
doi:10.1021/cr068046j.
E.M. Nolan, S.J. Lippard, Small-Molecule Fluorescent Sensors for Investigating Zinc
Metalloneurochemistry, Acc. Chem. Res. 42 (2009) 193–203. doi:10.1021/ar8001409.
H.N. Kim, M.H. Lee, H.J. Kim, J.S. Kim, J. Yoon, A new trend in rhodamine-based chemosensors:
application of spirolactam ring-opening to sensing ions, Chem. Soc. Rev. 37 (2008) 1465.
doi:10.1039/b802497a.
[7]
[8]
[9]
E.M. Nolan, S.J. Lippard, Tools and Tactics for the Optical Detection of Mercuric Ion, Chem. Rev. 108
(2008) 3443–3480. doi:10.1021/cr068000q.
S.K. Kim, D.H. Lee, J.-I. Hong, J. Yoon, Chemosensors for Pyrophosphate, Acc. Chem. Res. 42 (2009)
23–31. doi:10.1021/ar800003f.
S. Anbu, S. Kamalraj, B. Varghese, J. Muthumary, M. Kandaswamy, A Series of Oxyimine-Based
Macrocyclic Dinuclear Zinc(II) Complexes Enhances Phosphate Ester Hydrolysis, DNA Binding, DNA
Hydrolysis, and Lactate Dehydrogenase Inhibition and Induces Apoptosis, Inorg. Chem. 51 (2012)
5580–5592. doi:10.1021/ic202451e.
[10]
[11]
[12]
K.M. Acevedo, Y.H. Hung, A.H. Dalziel, Q.-X. Li, K. Laughton, K. Wikhe, A. Rembach, B. Roberts,
C.L. Masters, A.I. Bush, J. Camakaris, Copper Promotes the Trafficking of the Amyloid Precursor
Protein, J. Biol. Chem. 286 (2011) 8252–8262. doi:10.1074/jbc.M110.128512.
S.G. Aller, V.M. Unger, Projection structure of the human copper transporter CTR1 at 6-A resolution
reveals a compact trimer with a novel channel-like architecture., Proc. Natl. Acad. Sci. U. S. A. 103
(2006) 3627–32. doi:10.1073/pnas.0509929103.
Y. He, N.A. Jackman, T.L. Thorn, V.E. Vought, S.J. Hewett, Interleukin-1β protects astrocytes against
oxidant-induced injury via an NF-κB-dependent upregulation of glutathione synthesis., Glia. 63 (2015)
11

1568–80. doi:10.1002/glia.22828.
[13]
[14]
R. Dringen, I.F. Scheiber, J.F.B. Mercer, Copper metabolism of astrocytes., Front. Aging Neurosci. 5
(2013) 9. doi:10.3389/fnagi.2013.00009.
Z. Chen, H. Meng, G. Xing, C. Chen, Y. Zhao, G. Jia, T. Wang, H. Yuan, C. Ye, F. Zhao, Z. Chai, C.
Zhu, X. Fang, B. Ma, L. Wan, Acute toxicological effects of copper nanoparticles in vivo, Toxicol. Lett.
163 (2006) 109–120. doi:10.1016/j.toxlet.2005.10.003.
[15]
D. Huster, T.D. Purnat, J.L. Burkhead, M. Ralle, O. Fiehn, F. Stuckert, N.E. Olson, D. Teupser, S.
Lutsenko, High Copper Selectively Alters Lipid Metabolism and Cell Cycle Machinery in the Mouse
Model of Wilson Disease, J. Biol. Chem. 282 (2007) 8343–8355. doi:10.1074/jbc.M607496200.
[16]
[17]
[18]
[19]
J.F. Eisses, J.H. Kaplan, The mechanism of copper uptake mediated by human CTR1: a mutational
analysis., J. Biol. Chem. 280 (2005) 37159–68. doi:10.1074/jbc.M508822200.
S.G. Kaler, ATP7A-related copper transport diseases—emerging concepts and future trends, Nat. Rev.
Neurol. 7 (2011) 15–29. doi:10.1038/nrneurol.2010.180.
U.S Environmental Protection Agency, Prevention, Pesticides and Toxic Substances, June 2008, EPA
738-F-06-014.
H. Seo, M. An, B.-Y. Kim, J.-H. Choi, A. Helal, H.-S. Kim, Highly selective fluorescent probe for
sequential recognition of copper(II) and iodide ions, Tetrahedron. 73 (2017) 4684–4691.
doi:10.1016/J.TET.2017.06.034.
[20]
[21]
K. Li, M. Wang, Y. Hu, N. Xu, Q. Yu, Q. Wang, TAK1 knockdown enhances lipopolysaccharide-
induced secretion of proinflammatory cytokines in myeloid cells via unleashing MEKK3 activity, Cell.
Immunol. 310 (2016) 193–198. doi:10.1016/J.CELLIMM.2016.09.011.
U.N. Yadav, P. Pant, S.K. Sahoo, G.S. Shankarling, A novel colorimetric and fluorogenic chemosensor
2+
for selective detection of Cu
doi:10.1039/C4RA07552H.
ions in mixed aqueous media, RSC Adv. 4 (2014) 42647–42653.
[22]
[23]
Y.B. and, U. von Gunten*, Determination of Iodide and Iodate by Ion Chromatography with Postcolumn
Reaction and UV/Visible Detection, (1998). doi:10.1021/AC980658J.
M. Yu, M. Shi, Z. Chen, F. Li, X. Li, Y. Gao, J. Xu, H. Yang, Z. Zhou, T. Yi, C. Huang, Highly
12

2+
Sensitive and Fast Responsive Fluorescence Turn-On Chemodosimeter for Cu and Its Application in
Live Cell Imaging, Chem. - A Eur. J. 14 (2008) 6892–6900. doi:10.1002/chem.200800005.
[24]
[25]
[26]
[27]
[28]
[29]
J. Huang, Y. Xu, X. Qian, A red-shift colorimetric and fluorescent sensor for Cu2+ in aqueous solution:
unsymmetrical 4,5-diaminonaphthalimide with N-H deprotonation induced by metal ions, Org. Biomol.
Chem. 7 (2009) 1299. doi:10.1039/b818611a.
N. Moukrad, F.R. Filali, A. Amine, A. Hasan, A. Hamzi, Antibacterial effect of acridone and a series of
9-aminoacridine on seven pathogenic bacterial strains, International Journal of Recent Scientific
Research, 6, 9 (2015) 6134-6139.
P. Kumar, R. Kumar, D.N. Prasad, Synthesis and biological evaluation of new 9-aminoacridine-4-
carboxamide derivatives as anticancer agents: 1st Cancer Update, Arab. J. Chem. 6 (2013) 59–65.
doi:10.1016/J.ARABJC.2011.03.003.
C. Pal, M.K. Kundu, U. Bandyopadhyay, S. Adhikari, Synthesis of novel heme-interacting acridone
derivatives to prevent free heme-mediated protein oxidation and degradation, Bioorg. Med. Chem. Lett.
21 (2011) 3563–3567. doi:10.1016/j.bmcl.2011.04.127.
S.P. Prajapati, N.K. Kaushik, M. Zaveri, D. Mohanakrishanan, N. Kawathekar, D. Sahal, Synthesis,
characterization and antimalarial evaluation of new β-benzoylstyrene derivatives of acridine, Arab. J.
Chem. 10 (2017) S274–S280. doi:10.1016/J.ARABJC.2012.07.033.
R. Kumar, A. Sharma, S. Sharma, O. Silakari, M. Singh, M. Kaur, Synthesis, characterization and
antitumor activity of 2-methyl-9-substituted acridines, Arab. J. Chem. 10 (2017) S956–S963.
doi:10.1016/J.ARABJC.2012.12.035.
[30]
[31]
V. Rai-Constapel, M. Etinski, C.M. Marian, Photophysics of Xanthone: A Quantum Chemical Perusal, J.
Phys. Chem. A. 117 (2013) 3935–3944. doi:10.1021/jp401755j.
H. Hosseini Monfared, J. Sanchiz, Z. Kalantari, C. Janiak, Structure and magnetic properties of a
tetranuclear
Cu4O4 open-cubane
in
[Cu(L)]4·4H2O
with
L2− = (E)-N′-(2-oxy-3-
methoxybenzylidene)benzohydrazide, Inorganica Chimica Acta 362, 3791–3795 (2009).
[32]
S.P. Rawat and M. Choudhary, Synthesis, spectroscopic, magnetic properties and superoxide dismutase
(SOD) activity of copper (II) complexes with N-(2- hydroxy ethyl)-2-iminodiacetic acid and
polypyridine ligands, IOSR Journal of Applied Chemistry. 6(4), 25-31(2013).
13

[33]
[34]
N. Salem., El-Sayed L, Foro S, Haase., Iskander MF Metal complexes derived from hydrazoneoxime
ligands: III – Synthesis, characterization and electrospray ionization mass spectra of some nickel(II)
complexes with aroylhydrazoneoximes, Polyhedron 26: 4161–4172.
C.A. Heller, R.A. Henry, B.A. McLaughlin, D.E. Bliss, Fluorescence spectra and quantum yields.
Quinine, uranine, 9,10-diphenylanthracene, and 9,10-bis(phenylethynyl)anthracenes, J. Chem. Eng.
Data. 19 (1974) 214–219. doi:10.1021/je60062a002.
[35]
[36]
J. Salimon, N. Salih, E. Yousif, A. Hameed, A. Kreem, Synthesis and pharmacological evaluation of
9(10H)-acridone bearing 1,3,4-oxadiazole derivatives as antimicrobial agents, Arab. J. Chem. 3 (2010)
205–210. doi:10.1016/J.ARABJC.2010.06.001.
B. Valeur, I. Leray, Design principles of fluorescent molecular sensors for cation recognition, Coord.
Chem. Rev. 205 (2000) 3–40.
[37]
[38]
O. Stern and M. Volmer, über die Abklingzeit der Fluoreszenz, Zeitschrift Für Phys. 20 (1919) 183–188.
H. Boaz, G.K. Rollefson, The Quenching of Fluorescence. Deviations from the Stern-Volmer Law, J.
Am. Chem. Soc. 72 (1950) 3435–3443. doi:10.1021/ja01164a032.
[39]
[40]
[41]
Quenching of Fluorescence, in: Princ. Fluoresc. Spectrosc., Springer US, Boston, MA, 2006: pp. 277–
330. doi:10.1007/978-0-387-46312-4_8.
M.S. Matos, J. Hofkens, M.H. Gehlen, Static and Dynamic Bimolecular Fluorescence Quenching of
Porphyrin Dendrimers in Solution, J. Fluoresc. 18 (2008) 821–826. doi:10.1007/s10895-007-0309-7.
O. Duman, S. Tunç, B. Kancı Bozoğlan, Characterization of the Binding of Metoprolol Tartrate and
Guaifenesin Drugs to Human Serum Albumin and Human Hemoglobin Proteins by Fluorescence and
Circular Dichroism Spectroscopy, J. Fluoresc. 23 (2013) 659–669. doi:10.1007/s10895-013-1177-y.
[42]
[43]
S. Tunç, O. Duman, İ. Soylu, B. Kancı Bozoğlan, Study on the bindings of dichlorprop and diquat
dibromide herbicides to human serum albumin by spectroscopic methods, J. Hazard. Mater. 273 (2014)
36–43. doi:10.1016/J.JHAZMAT.2014.03.022.
B.K. Bozoğlan, S. Tunç, O. Duman, Investigation of neohesperidin dihydrochalcone binding to human
serum
albumin
by
spectroscopic
methods,
J.
Lumin.
155
(2014)
198–204.
doi:10.1016/J.JLUMIN.2014.06.032.
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15

Highlights
- A new chemosensor S1 was facilely synthesized by Schiff base condensation from acridone.
- S1 showed highly selective fluorescence turn-off sensing towards Cu2+ in aqueous media.
- The detection limit sensing for Cu2+ in aqueous media was estimated to be 0.80 µM.