A novel quinazolinone derivative as fluorescence quenching off-on sensor for high selectivity of Fe3+

Article abstract of DOI:10.1007/s10895-013-1325-4

A novel quinazolinone compound containing quinazoline-fused moiety has been synthesized as fluorescence Off-On sensor QQ. The probe exhibited highly selective and sensitive recognition toward trivalent ferric ion (Fe ³⁺) over other metal ions i

Full text of DOI:10.1007/s10895-013-1325-4

J Fluoresc (2014) 24:557–561
DOI 10.1007/s10895-013-1325-4
ORIGINAL PAPER
A Novel Quinazolinone Derivative as Fluorescence Quenching
Off-On Sensor for High Selectivity of Fe3+
Ailin Yuan & Chunling Zheng & Zhengyu Zhang &
Lu Yang & Chao Liu & Haibo Wang
Received: 23 August 2013 /Accepted: 7 November 2013 /Published online: 5 December 2013
#
Springer Science+Business Media New York 2013
Abstract A novel quinazolinone compound containing
quinazoline-fused moiety has been synthesized as fluores-
cence Off-On sensor QQ. The probe exhibited highly selective
and sensitive recognition toward trivalent ferric ion (Fe3+)
over other metal ions in HEPES buffer solution (10 mM,
pH=7.0, DMF-H2O, 9:1, v/v). The significant quenching in
the fluorescence spectral could be served as a selective fluo-
rescence Off-On sensor. The titration study indicated the
formation of 1:1 complex between QQ and Fe3+.
the reports about fluorescent probes for Fe3+ are rarely seen in
recent years.
The quinazoline ring system along with many alkaloids is a
widely recognized moiety in organic syntheses and medioinal
applications. It has been reported that modification of
quinazoline structure could be applied in many biological
studies, such as anticonvulsant, antibacterial, antidiabetic,
and anticancer [12, 13]. Quinazoline derivatives act as pow-
erful inhibitors of epidermal growth factor (EGF) receptors of
tyrosine kinase. Quinazolinones are excellent reservoir of
bioactive substances. Several bio-active natural products such
as febrifugine and isofebrifugine contain quinazolinone moi-
eties with potential antimalarial activity [14, 15]. In addition,
quinazoline ketone compounds are also good chemical sen-
sors because of their larger fluorescence intensity and good
light stability. Therefore, phenyl iso-thiocyanate was intro-
duced to β-position of quinazoline ketone ring. In this paper
to synthesize a novel quinazolinone compound containing
quinazoline-fused moiety (QQ), which showed favourable
recognition response to Fe3+ and could be applied as fluores-
cence Off-On sensor for high selectivity of Fe3+.
3+
.
.
.
Keywords Quinazolinone Fe Fluorescentprobe Off-On
Introduction
The development of fluorescent artificial receptors for the
recognition of biologically and environmentally important
ions (including metal ions and anions) has received numerous
attention due to their basic roles in a wide range of chemical,
environmental, and biological processes [1–3]. Nowadays,
researchers have synthesized some fluorescent probes to de-
termine such metal ions as Cu2+, Fe3+, Zn2+, Cd2+, Hg2+, and
Pb2+ in organisms [4–7]. Fe3+ is widely distributed in nature
and is one of the most important elements in biological sys-
tems, which participates in many biochemical processes at the
cellular level. It is an essential element for the formation of
hemoglobin of red cells and plays an important role in the
storage and transport of oxygen to tissues. Therefore, research
of fluorescent probes for Fe3+ detection is of great significance
to environmental and biological sciences [8–11]. However,
Experiment
Materials and General Methods
All the reagents and solvents were purchased from commer-
cial sources and were of analytical grade. Solvents were dried
according to standard procedures. All reactions were magnet-
i c a l l y s t i r r e d a n d m o n i t o r e d b y t h i n - l a y e r
chromatography(TLC). Melting points(M.p.) of prepared
compounds were measured on an X4 micromelting point
:
:
:
:
:
A. Yuan C. Zheng Z. Zhang L. Yang C. Liu H. Wang (*)
Institute of Food and Light-chemical Engineering, Nanjing, Jiangsu,
China
1
apparatus. A BRUKER DRX500 spectrometer recorded H
NMR spectra of objective products. Fluorescence spectra
e-mail: wanghaibo@njut.edu.cn

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J Fluoresc (2014) 24:557–561
were taken on an Perkin Elmer LS −55 type fluorescence
photometer.
pressure and heated to reflux, the filtered solid was recrystal-
lized to yield light yellow product(0.53 g, 2.0 mmol, 77.9 %)
by column chromatography(petroleum ether:ethyl acetate=
3:1), M.p.,210-212.1H NMR(500 MHz, DMSO-d6) δ=
12.81(s, 1H), 7.66(d, J =8 Hz,1H), 7.57–8.23(m, 3H), 7.81–
7.93(m, 4H).
Synthesis
Synthetic procedures of QQ were shown in Scheme 1.
N-(2-nitrophenyl)phthalamide (1) Anthranilamide (1.04 g,
8.5 mmol), triethylamine (3.1 mL, 17 mmol), and
chloroform(25 mL) was added into a 100 mL four-neck flask
and stirred at room temperature, then 2-Nitrobenzamide was
added dropwise into the solution. the refluxing reaction lasted
4 h at room temperature until TLC indicated the end of
reaction, cooling down, recrystallization for filtered solid with
methanol would give white crystal (0.68 g, 2.4 mmol,
2-(2-aminophenyl)quinazolin-4(3H)-one (3) 2(0.6 g,
2.2 mmol), SnCl2(1.01 g, 4.5 mmol) and methanol(25 mL)
were put into a 100 mL four-neck flask and heated. The
refluxing reaction lasted until TLC indicated the complete
transformation, then was cooled down. Recrystallization for
filtered solid from deionized water would afford yellow crys-
tal (0.52 g, 2.2 mmol, 86.7 %). M.p., 224–226 °C. H
NMR(500 MHz, DMSO-d6) δ=12.01 (s, 1H), 7.02(s, 2H),
7.71–8.14(m, 4H), 6.59–7.50(m, 4H).
1
1
65.3 %), M.p.,190–192 °C. H NMR(500 MHz, DMSO-d6)
δ=8.48(d, J =8 Hz, 1H), 8.11(d, J =8.5 Hz,1H), 8.34(s, 1H),
7.34(s, 1H), 12.49(s, 1H), 7.58(t, J =8 Hz, 1H), 7.21–7.24(m,
1H), 7.74–7.90(m, 5H).
2-(2-nitrophenyl)quinazolin-4(3H)-one (2) 1(0.68 g,
2.4 mmol), ethanol(10 mL) and potassium hydroxide solution
(10 %) were added into a 100 mL four-neck flask, heated to
reflux for 15 m. Then ethanol was removed under reduced
QQ (4) 3(0.1 g, 0.4 mmol) and acetone (25 mL) were put
into a 100 mL four-neck flask firstly, following phenyl iso-
thiocyanate (0.15 mL/0.17 g, 1.26 mmol) was added in the
solution dropwise. The system was heated and refluxed for 12 h
until the complete reaction was monitored by TLC, then was
cooled down. The filtered result was earthy yellow solid(0.16 g,
0.48 mmol, 60 %). M.p., 288 °C~290 °C. 1H NMR(300 MHz,
CONH2
Scheme 1 Synthetic procedures
of QQ
NH2
CONH2
NO2
CHCl3
reflux
CONH
NO2
NO2
HOOC
ClOC
SOCl2
reflux
1
O
O
NH
NH2
NH
NO2
KOH
EtOH
SnCl2
N
reflux
N
3
2
O
N
HN
NCS
N
N
acetone
4

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559
Fig 1 Fluorescence emission spectra of QQ in the presence of
Fig 3 Relative fluorescence intensity changes of QQ in the presence of
various metal ions (20 eq.) and Fe3+ (20 eq.) in HEPES buffer solution
(10 mM, pH=7.0, DMF-H2O, 9:1, v/v).λex=344 nm
Fe3+ in HEPES buffer solution (10 mM, pH=7.0, DMF-H2O, 9:1, v/v),
λex=344 nm
DMSO-d6)δ=12.28 (s, 1H), 8.57(d, J =8.1 Hz,1H), 8.34(d, J =
8.1 Hz, 1H), 8.01(t, J =7.8 Hz, 1H), 7.15 ppm(t, J =7.5 Hz,
1H), 7.33–7.46(m, 4H), 7.59–7.90(m, 5H).
PC running SpectraCalc software package. All measurements
were carried out in HEPES buffered (10 mM, pH=7.0, DMF-
H2O, 9:1, v/v).
Fluorescence Sensing of QQ for Metal Ions
Deionized water was used throughout all experiments.
Solutions of Fe3+, Pb2+, Cu2+, Ag+, Zn2+, Hg2+, Ba2+, Fe2+,
Cr3+, Cd2+, Mg2+, Mn2+, Co3+, Ni2+, K+, Na+, and Bi3+ were
prepared from their nitrate salts. A 1 mM stock solution of QQ
was prepared by dissolving in DMF. All measurements of
fluorescence spectra(FS) were obtained with a Perkin Elmer
LS-55 fluorescence spectrophotometer linked to a Pentium
Chemical Complexion Stoichiometric Ratio of QQ and Fe3+
In the titration experiments, a 2.5 mL solution of QQ (10 mM
and 1 mM) was poured into a quartz optical cell of 1 cm
optical path length each time, and Hg2+solution was added
into the quartz optical cell gradually with a micro-pipette. FS
data were recorded in an indicated time after the addition.
Fig 2 a Relative fluorescence intensity changes of QQ in the presence of
various metal ions(10 eq.) in HEPES buffer solution (10 mM, pH=7.0,
DMF-H2O, 9:1, v/v), λex=344 nm. b Fluorescence spectra of QQ in the
presence of various equiv of Fe3+ in HEPES buffer solution (10 mM,
pH=7.0, DMF-H2O, 9:1, v/v).λex=344 nm

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J Fluoresc (2014) 24:557–561
Titration experiments were carried out and Job’s analyses
[16] was applied to calculate the stoichiometric ratio of QQ-
Fe3+ complex according to the following equation.
9:1, v/v) at an excitation wavelength of 344 nm. Figure 1
shows a change in the fluorescence spectra of QQ. When no
metal ion was added to the solution, almost no fluorescence
signal in the range from, 300 nm to 500 nm could be observed,
whereas a significant quenching of the characteristic fluores-
cence could be found soon after Fe3+ was injected into the
solution.
Â
Ã
F−Fmin
Fmax−F
log
¼ nlog Fe3þ þ B
In above equation, Fmin , Fmax and F were the fluorescent
intensity of metal-free QQ, QQ with excessive Fe3+and QQ
with Fe3+at any concentration between the former two,
resperively. n meant the stoichiometry of QQ- Fe3+complex.
Fluorescence Sensing of QQ for Fe3+
The Fig. 2a is fluorescence spectra of quinazoline QQ in
HEPES buffer with appropriate amounts of metal ions.
Solutions were shaken for 30 min before measuring the ab-
sorption and fluorescence in order to make the metal ions
chelate with the sensors sufficiently. Under the identical con-
dition, no obvious response could be observed upon the
addition of other ions including Al3+, Ba2+, Cd2+, Cr3+,
Fe2+, Hg2+, K+, Mg2+, Mn2+, Na+, Pb2+ and Zn2+. It shows
that the fluorescence selective of QQ to Fe3+ is very
Results and Discussion
Spectroscopic Properties of QQ
Fluorescence and UV–vis studies were performed using a
solution of quinazoline QQ in HEPES buffer (DMF-H2O
a
b
c
0.85
0.12
0.1
0.75
0.65
0.55
0.45
0.35
0.08
0.06
0.04
0.02
0
0
0.5
1
1.5
2
2.5
3
0
0.2 0.4 0.6 0.8
1
1.2
[Fe3+]/[QQ]
[Fe3+]/([QQ]+[Fe3+])
Fig 4 a Curve of fluorescence intensity at 344 nm of QQ versus increasing concentration of Fe3+. b Absorbance of QQ-Fe3+ complex in different [Fe3+
]/[QQ] ratio. c Job’s plot for the QQ-Fe3+ complex ([QQ]+[Fe3+]=5×10−5 mol dm−3
)

J Fluoresc (2014) 24:557–561
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specificity. It is probably due to several combined influences
cooperating to achieve the unique selectivity for the Fe3+ ion,
such as the suitable coordination geometry conformation of
the receptor, the radius of the Fe3+ ion and the amide depro-
tonation ability of the Fe3+ ion.
Conclusions
In conclusion, a quinazoline ketone compound has been syn-
thesised as fluorescence probe QQ for Fe3+ detecting. The ion
binding properties of this receptor with a large number of
metal ions have been investigated and the ion recognition
events have been monitored by fluorescence spectral changes.
Our study revealed that the fluorescence selective of QQ to
Fe3+ is high selectivity and anti-disturbance. The calculation
confirmed that a stable 1:1 QQ-Fe3+complex formed.
With gradual addition of Fe3+ ion to the solution of QQ, the
fluorescence intensity was decreased obviously. Due to the
formation of chelate Fe3+ with cavity of N and polycyclic in
molecular structure of QQ, it caused the decline of coplanarity
and molecular rigidity of QQ result in the fluorescence
quenching. Figure 2b shows that emission peak recede grad-
ually with the addition of Fe3+, but the peak patterns do not
shift. When the titration achieves a balance, the fluorescence
tensity declines three times.
Acknowledgments Financial support from General Program of Open
Foundation of Zhejiang Provincial Top Key Academic Discipline of
Applied Chemistry and Eco-Dyeing & Finishing Engineering (Grant
No. YR2012016), and the Open Project Program of Key Laboratory of
Eco-textiles, Ministry of Education, Jiangnan University (Grant No.
KLET1201) are gratefully acknowleged.
Interference Test
The solution of QQ showed almost no changes in the presence
of other metal ions, such as Al3+, Cu2+, Ba2+, Cd2+, Cr3+, Fe2+,
Hg2+, K+, Mg2+, Mn2+, Na+, Pb2+ and Zn2+. The results show
that the selective recognition of QQ to Fe3+ is hardly interfered
with common metal ions. The evidence supports that QQ can
serve as a selective OFF-ON fluorescence (Fig. 3).
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Chelation curve of log((F-Fmin/(Fmax-F)) and log[Fe3+] is
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with Fe3+ is calculated to be Kα=6.89×103.