Fluorescent turn-on sensors based on pyrene-containing Schiff base derivatives for Cu2+recognition: spectroscopic and DFT computational studies

Article abstract of DOI:10.1016/j.tet.2016.06.017

A new fluorescent chemosensor L1, a pyrene containing a long chain Schiff base derivative at the 1-position has been synthesized. Similarly, the receptors L2 and L3 are also designed in order to compare the binding ability for detection of Cu²⁺. The receptors exhibit very weak fluorescence (Φ=0.01) due to the photoinduced electron transfer (PET). Upon addition of 10?equiv of Cu²⁺, the emission intensity of ligands L1 and L2 are increased 65-fold (Φ=0.31) and 25-fold (Φ=0.08) in CH₃CN/CH₂Cl₂solvents system, respectively. NMR titration experiments, spectroscopic and DFT computational studies confirmed the binding phenomena and sensitivity of Cu²⁺.

Full text of DOI:10.1016/j.tet.2016.06.017

Accepted Manuscript
Fluorescent turn-on sensors based on pyrene-containing Schiff base derivatives for
2+
Cu recognition: spectroscopic and DFT computational studies
Zannatul Kowser, Cheng-Cheng Jin, Xuekai Jiang, Shofiur Rahman, Paris E.
Georghiou, Xin-Long Ni, Xi Zeng, Carl Redshaw, Takehiko Yamato
PII:
S0040-4020(16)30530-0
10.1016/j.tet.2016.06.017
TET 27831
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 25 May 2016
Accepted Date: 6 June 2016
Please cite this article as: Kowser Z, Jin C-C, Jiang X, Rahman S, Georghiou PE, Ni X-L, Zeng X,
Redshaw C, Yamato T, Fluorescent turn-on sensors based on pyrene-containing Schiff base derivatives
2+
for Cu recognition: spectroscopic and DFT computational studies, Tetrahedron (2016), doi: 10.1016/
j.tet.2016.06.017.
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Fluorescent turn-on sensors based on pyrene-containing Leave this area blank for abstract info.
2
+
Schiff base derivatives for Cu recognition:
Spectroscopic and DFT computational studies
a
a
a
b
b
c
Zannatul Kowser, Cheng-Cheng Jin, Xuekai Jiang, Shofiur Rahman, Paris E. Georghiou, Xin-Long Ni, Xi
c
d
a
Zeng, Carl Redshaw and Takehiko Yamato*
a
Department of Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi 1, Saga
40-8502, Japan
8
b
Department of Chemistry, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador,
Canada A1B3X7
c
Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University,
Guiyang 550025, People’s Republic of China
d
Department of Chemistry, The University of Hull, Cottingham Road, Hull, Yorkshire, HU6 7RX, UK

2
Tetrahedron
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Tetrahedron
journal homepage: www.elsevier.com
Fluorescent turn-on sensors based on pyrene-containing Schiff base derivatives for
2
+
Cu recognition: Spectroscopic and DFT computational studies
a
a
a
b
b
c
Zannatul Kowser, Cheng-Cheng Jin, Xuekai Jiang, Shofiur Rahman, Paris E. Georghiou, Xin-Long Ni,
c
d
a
Xi Zeng, Carl Redshaw and Takehiko Yamato*
a
Department of Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi 1, Saga 840-8502, Japan
Department of Chemistry, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada A1B3X7
Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University,Guiyang 550025, People’s Republic of China
Department of Chemistry, The University of Hull, Cottingham Road, Hull, Yorkshire, HU6 7RX, UK
b
c
d
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A new fluorescent chemosensor L1, pyrene containing long chain Schiff base derivative in 1-
position has been synthesized. Similarly, the receptors L2 and L3 are also designed in order to
2
+
compare the binding ability for detection of Cu . The receptors exhibit very weak fluorescence
2
+
(
Φ = 0.01) due to the photoinduced electron transfer (PET). Upon addition of 10 equiv. of Cu ,
the emission intensity of ligands L1 and L2 are increased 65-fold (Φ = 0.31) and 25-fold (Φ =
0.08) in CH CN/CH Cl solvents system respectively. NMR titration experiments, spectroscopic
and DFT computational studies confirmed binding phenomena and sensitivity of Cu .
Available online
Keywords:
3
2
2
2+
Pyrene-based Schiff base derivatives
Fluorescent turn-on sensor
High selectivity and sensitivity
DFT computational studies
2
009 Elsevier Ltd. All rights reserved.
1
. Introduction
growing interest. Of the sensors reported to-date, several advantages
for fluorescent chemosensors over other methods have been noted.
These include their sensitivity, specificity and real time monitoring
The development of selective and sensitive chemosensors for the
10
recognition of cations and anions of biological interest has been a
subject of current research in recent years given that they play an
important role in many environmental and biological processes.
Amongst the various essential metal ions in the human body, copper
is the third most abundant transition metal ion. Copper as a catalytic
cofactor, plays a crucial role for a variety of metal enzymes
including superoxide dismutase, cytochrome oxidase and tyrosinase.
However, if excessive amounts are ingested, exposure to a high level
of copper may result in neurodegenerative diseases as it is involved
in the production of reactive oxygen species. Furthermore, in
addition, high levels of ingested copper causes gastrointestinal
disturbance even when present for a short period of time, whilst over
longer periods, liver or kidney damage may also occur. Thus
although copper is essential for life, it can also be highly toxic to
with a fast response time. Although fluorescent chemosensors for
11
the copper ion have been widely investigated, there are still only
1
–4
12
2+
some examples of “off-on” sensors. As Cu is a fluorescence
13
quencher, owing to its paramagnetic nature, most fluorescent
2+
sensors bind Cu by the fluorescence quenching process which
14
involves a charge-, or energy-transfer mechanism. Fluorescence
quenching is unfavourable for a high signal output and also hampers
the temporal separation of spectroscopically similar complexes with
15
time-resolved fluorometry. Considering this factor, Yoon et al.
have synthesized a highly selective and ratiometric ‘off-on’ sensor,
5
2+
16
namely a rhodamine-pyrene derivative for Cu detection.
Many fluorescence mechanisms have also been reported based on
photoinduced electron transfer (PET), intermolecular charge transfer
(ICT), excited state intramolecular proton transfer (ESIPT), excimer
formation and non-coordinative interations between a ligand and the
metal ion. In the case of PET, there is little or no change of the
spectral shifts with changes of emission intensities, whereas both
spectral shifts and intensity changes are observed for ICT, ESIPT
also shows fluorescence enrichment with or without accompanying
spectral changes. Furthermore, excimer emission typically provides
a broad fluorescence band without vibrational structure, with the
6
2
+
organisms. For these reasons, Cu is one of the most frequently
studied metal ions of the first row transition metals in the area of
chemosensors.
constant with ligands which contain oxygen or nitrogen donor
atoms. Therefore, the development of highly selective chemosensors
7,
8
2+
Beside this, Cu has the highest formation
9
for the copper ion in the presence of various metal ions is attracting
*
Corresponding author. Fax: +81 952 28 8548; e-mail address: yamatot@cc.saga-u.ac.jp
17
maximum shifted, in the case of most aromatic molecules. In order
(
T. Yamato).

to develop the fluorescence intensity enhancement of the receptor
was present in L2 whilst only a phenylimino moiety instead of a
ACCEPTED MANUSCRIPT
2+
upon binding of Cu via a photoinduced intramolecular electron
transfer, one needs to carefully choose or design the receptor
molecule containing a fluorophore. The fluorescence quenching
needs to be maximized in the free receptor responsible for the PET,
hydrazido carbonyl group was present in L3. Ligands L1 and
2
+
L2 can bind and sense Cu by fluorescence through the
coordination bond with the hydrazidocarbonyl group, following
a 1:1 ligand to metal binding mode. Interestingly, in case of
ligand L1, the upper part, N,N-diethylaminocarbonylmethoxy
2+
whereas the PET should be minimized in the Cu -bound state of the
receptor. Among different fluorophore units, pyrene is the most
useful due to its high fluorescence quantum yield, chemical stability,
and long fluorescence lifetime. Additionally, pyrene exhibits
monomer-excimer dual fluorescence, and the fluorescence intensity
ratio of the monomer-to-excimer emission is sensitive to
2+
group has prominent effect upon binding with Cu .
The probes show very weak fluorescence (Φ = 0.01) at 405
2
+
nm due to PET. When binding with Cu , ligand L1 induces a
blue emission (intensity Φ = 0.31) by inhibiting the PET, and
the emission intensity is approximately 65 times greater than
that of the free ligand. Furthermore, in comparison with the
11a,18
conformational changes of the pyrene-functionalized system.
Consequently, several pyrene-based sensors have been constructed
2+
receptors L2 and L3, ligand L1 is highly sensitive for Cu
19
for metal ion detection. Based on monomer-excimer conversion, a
pyrene chemosensor containing a thiophene moiety was a highly
selective and ratiometric fluorescent sensor which induces the dual
appearance of excimer emission and disappearance of monomer
detection due to the strong inhibition of PET and the different
binding phenomenon of ligand to metal complex.
2. Results and discussions
2.1. Synthesis
2+
20
emission after addition of Cu ion. Venkatesan and Wu. have
designed a pyrene-based fluorescent probe bearing the hydrazinyl
2+
pyridine moiety for Cu ion detection based on the PET mechanism.
The chemosensors binding with the metal ion block the PET
The synthetic pathways of the fluorogenic molecules L1, L2 and
L3 are similar, and are summarized in Scheme 1. The amidation of
compound 1 was carried out with hydrazine in a solution mixture of
EtOH to synthesize 4-(hydrazidocarbonyl)(N,N-diethylaminocar-
bonylmethoxy)benzene 2. Compound 2 was then condensed with 1-
pyrenecarbaldehyde to give L1. Following a similar reaction
pathway, the reference compound L2 was prepared from ethyl-p-
21
mechanism resulting in significant fluorescence enhancement.
Furthermore, Wu et al. have developed a highly selective turn-on
2+
fluorescence sensor for Cu detection in living cells, in which the
2+
picolinohydrazide act as a chelator and can bind to Cu through two
functional groups, namely the amide nitrogen atom and the pyridine
22
nitrogen atom.
2+
anisate in order to compare the binding affinities for Cu . Ligand L3
On the basis of the above, we have focused our interest on
designing molecules which can serve as receptors to recognize
cations based on a fluorescence ‘off-on’ mechanism. In this
regard, we have utilized Schiff base derivatives in which a
hydrazido carbonyl group binds with the pyrene moiety, whilst
a diethylaminocarbonylmethoxy group forms the upper part of
the phenyl ring for the formation of the receptor ligand L1
was also synthesized from the condensation reaction of Py-CHO
with 4-methoxyanisidine. Reference compounds L2 and L3 were
23
24
prepared following the reported procedures. The structures of
1
13
compounds L1, L2 and L3 were characterized by H and C NMR
spectroscopy and are given in the ESI (Figures. SI 16–SI 20). IR
spectra, FAB-MS and elemental analysis were taken to confirm the
structure of ligand L1.
(
Scheme 1). Receptors L2 and L3 were also synthesized: a
methoxy instead of the diethylaminocarbonylmethoxy group
2.2. Binding studies
At first, the cation-binding properties of compounds L1, L2 and
L3, featuring the Schiff-base sites and armed with the pyrene moiety,
were characterized by spectroscopic measurements. These were
carried out in CH CN/CH Cl (1000:1, v/v) by addition of different
3
2
2
+
+
+
+
+
2+
2+
2+
2+
2+
metal cations Li , Na , K , Cs , Ag , Zn , Cu , Pb , Hg , Fe and
Fe (perchlorate salts), Ni , Cd , Co , Cr (nitrate salts)
3+
2+
2+
2+
3+
dissolved in CH CN. As shown in Fig. 1, the UV−vis absorption
3
Scheme 1 Synthesis of receptors L1, L2 and L3.
Fig. 1 UV-vis spectra of ligand L1 (10.0 µM) in CH
3
CN/CH
2 2
Cl (1000:1, v/v)
2+
upon addition of 10 equiv. of Cu metal ions as their aqueous solution.

4
Tetrahedron
ACCEPTED MANUSCRIPT
Fig. 2 Fluorescence response of ligands L1, L2 and L3 (1.0 ꢀM) upon
2+
Fig. 3 Fluorescence spectra of ligand L1 (1.0 µM, λex = 367 nm) upon
addition of various metal ions (10 equiv.) as their CH CN solutions.
addition of Cu ions (10 equiv.) measured in CH
3 2 2
CN/CH Cl (1000:1, v/v).
3
λex = 367 nm.
spectra of ligand L1 exhibited typical pyrene absorption bands at
77 and 349 nm along with a LE broad band centered at 367 nm,
and the limitations of the B-H method has been well-addressed in
25a,b
2
the literature.
The global analysis approach offers a more
attributed to the hydrazido carbonyl group as well as the
diethylaminocarbonylmethoxy group of the upper part. Upon
accurate determination of the equilibria involved since it avoids the
manipulation of the actual experimental data to effect linear
relationship was observed between the fluorescence intensity and
2+
addition of up to 10 equiv. of Cu to the solution of ligand L1, the
absorbance at 367 nm decreased progressively and at the same time,
a new UV−vis absorption band at around 430 nm was observed; two
identical isosbestic points were observed at around 305 and 410 nm
2+
the concentration of Cu showing a low detection limit of 8.80 ×
–8
26a
10 M. This value is much lower than the concentration allowed
20
in drinking water according to the US EPA (20 µM). Furthermore,
2+
2+
indicating the presence of a unique complex after addition of Cu .
The resulting titration data suggests strong interactions between
when excited at 367 nm, the quantum yield, Φ, of the L1-Cu
complex was 0.31 which was 31-fold more enhanced than of free
2+
26b
2+
ligand L1 and Cu .
ligand L1 alone. The fluorescence titration experiments of Cu
complex was 0.31 which was 31-fold more enhanced than of free
Ligands L1, L2 and L3 (1.0 µM, λex = 367 nm) showed only very
weak fluorescence in CH CN/CH Cl (1000:1, v/v). The emission
26b
2+
ligand L1 alone. The fluorescence titration experiments of Cu
with L2 were also conducted in the same CH CN/CH Cl solvent
3
2
2
intensity of the pyrenyl fluorophore is quenched because the lone
pair electrons from the nitrogen atoms are transferred to the excited
3
2
2
mixture and revealed an 8-fold enhancement in the quantum yield
2+
25a
pyrenyl moiety. After the addition of small concentrations of Cu ,
preferential binding occurs to terminate the PET. Before and after
over the free ligand L2 (Figure SI 6). The global fit analysis
(Figure SI 10) for the binding or association constant of L2 was
2+
4
–1
addition of Cu , the fluorescence intensity changes of ligand L1 are
compared with L2 and L3 and it can be seen that the free ligand L1
exhibits higher fluorescence intensity than L2 and L3 (Figure SI 8).
determined to be 1.55 × 10 ± 0.24% M (cov fit < 0.01) and was
–7
found to have a detection limit of 4.94 × 10 M (Figure SI 12). In
this case, the quantum yield is enhanced only 8-fold after addition of
Cu (Φ = 0.08). On the other hand, the minor changes in the
2+
2+
Fig. 2 shows that after addition of Cu , the fluorescence intensity is
predominantly enhanced. In the case of L1, which is enhanced
approximately 40 times more than L2 and 57 times more than L3.
This suggests that PET occurs predominantly in L3 versus L2 and
then L1. To elucidate the binding properties of L1 towards other
metal ions, the fluorescence changes upon addition of a wide range
of metal cations (10 equiv.) using their perchlorate salts and nitrate
fluorescence titration spectra of L3 indicate the very weak
2+
coordination with Cu (Figure SI 7). There are also insignificant
changes of the photophysical properties of ligand L3. These results
confirm that ligand L1 is more sensitive and exhibits a stronger
2+
affinity toward Cu than L2 and L3 in CH CN/CH Cl (Table 1).
3 2 2
salts in CH CN solution were determined. As shown in Fig. 3, ligand
3
2+
L1 exhibited high selectivity toward Cu ions. By contrast, the
addition of different metal cations Li , Na , K , Cs , Ag , Zn , Cu ,
Pb , Hg , Fe , Fe , Ni , Cd , Co and Cr resulted in almost
no fluorescence enhancement.
The binding property of probe L1 with Cu (Fig. 4) was then
+
+
+
+
+
2+
2+
2+
2+
2+
3+
2+
2+
2+
3+
2+
determined by a fluorescence titration experiment. When excited at
3
67 nm, L1 displayed a weak emission band at about 405 nm. The
2+
stepwise addition of Cu leads to an increase of fluorescence
intensity. The fluorescence intensity is increased by 65-fold upon the
addition of 10 equiv. of Cu in CH CN/CH Cl (1000:1, v/v) The
2+
3
2
2
resulting binding or association constant determined by a global
2
5a
2+
5
analysis , for the L1-Cu complexation, was 1.29 × 10 ± 0.32%
M
–1
value. The covariance of fit value was < 0.01 which is a
Fig. 4 Fluorescence spectra of ligand L1 (1.0 ꢀM) upon addition of
reasonably good fit of the data to the 1:1 binding model (Figure SI 9).
The Benesi-Hildebrand plot gave a smaller value of 6.12 × 10 M
2+
increasing concentration of Cu
ions (0–10 equiv.) measured in
4
–1
CH CN/CH Cl (1000:1, v/v). λ = 367 nm.
3
2
2
ex

2
+
Table 1. Photophysical properties of ligands L1, L2 and L3 with their Cu
and 0.54 ppm for the pyrene proton H , and the phenyl ring proton
H respectively (Table 2). The other phenyl ring protons also shifted
d,
ACCEPTED MANUSCRIPT
c
complexes.
from δ = 8.12 ppm to δ = 8.30 ppm. These protons are broad and
have lower intensities. The phenyl proton shifts are due to the
inductive effect of the diethylaminocarbonylmethoxy group which
overlapped with other pyrene protons. Moreover, the methylene
proton H and ethyl protons H and H also underwent slight upfield
-
1 a
b
c
d
Comp.
K (M )
LODs (M)
Φ
(Φ) enhanced
a
2
2
2
+
+
+
5
-8
L1⊃ Cu
L2⊃ Cu
L3⊃ Cu
1.29 × 10 8.80 × 10
0.31
0.08
0.01
31-fold
8-fold
NA
e
g
f
4
-7
1.55 × 10 4.94 × 10
shifts of 0.05 and 0.06 and 0.04 ppm, respectively. In contrast, in
1
order to clarify the co-ordination structure of ligand L1, H NMR
NA
NA
2
+
analysis of ligand L2 was also performed in presence of Cu ion
a
b
(Figure SI 14). In this case, like with ligand L1, the amide proton, Ha
K = Association constant; LODs = Detection limits (measured from
a
c
2
+
fluorescence titration experiments); Φ = Quantum yield of L1⊃ Cu ; (Φ)
and imine proton H of L2 disappeared due to the paramagnetic
b
d
enhanced = Difference between the quantum yield of free ligand and after
2+
2+
nature of Cu . On the other hand, the pyrene proton H and the
addition of Cu ; NA means fluorescence change was scarcely observed;
photophysical properties cannot be calculated.
c
phenyl ring proton H induced smaller downfield shift of 0.16 and
d
2+
0
.26 ppm than with ligand L1⊃ Cu . The other phenyl ring protons
Moreover, the association constant of the pyrene containing the
3
–1 22
overlapped with the pyrene protons and the chemical shifts remain
unchanged. In addition to this, there is no change in the methoxy
proton He which signifies that the methoxy protons have no
picolinohydrazide moiety was found to be 2.75 × 10 M . On the
basis of the findings above, it is suggested that ligand L1 is a highly
sensitive fluorescent probe than L2 and L3 in CH CN/CH Cl
3
2
2
2
+
2+
contribution to the binding. These results indicate that Cu ions are
only bound to the imine nitrogen atom and the amide carbonyl
(
1000:1, v/v). The coordination of Cu with the Schiff base site
presumably caused the inhibition of PET effect which was much
stronger than any cavity-control effect. Furthermore, upon addition
of metal ions (10.0 µM) to the receptor L1 (1.0 µM) and Cu (10.0
µM), all of the competitive cations caused no significant interference
at higher concentration. These results indicate that L1 displays an
2
+
oxygen of ligand L2. Also, up to the addition of 1 equiv. of Cu , the
prominent changes which were monitored represent 1:1 complexes.
Furthermore, to gain a further understanding of the binding
2+
2+
13
stoichiometry of L1 and Cu
complex, C NMR titration
2+
experiments were carried out in a mixture of CDCl /DMSO
3
excellent selectivity toward Cu over the other metal cations (Fig.
5
2+
). In order to quantify the stoichiometry of the complexes L1-Cu ,
a Job’s plot analysis was carried out in which the emission of the
complexes at 405 nm were plotted against molar fractions of L1 and
2+
Cu under the conditions of an invariant total concentration. The
fluorescence intensity shows a maximum at the mole fraction 0.5
2+
which corresponds to a 1:1 ratio of L1⊃ Cu complex (Figure SI 13).
1
A H NMR spectroscopic analysis with L1 was performed to
2+
investigate the nature of the co-ordination structure of L1 and Cu .
Since the receptor L1 was only partially soluble in CD CN/CDCl , a
3
3
9
:3 ratio of CDCl /DMSO-d6 was employed for these analyses.
3
Copper ion has paramagnetic nature, therefore when binding occurs,
the proton signals close to the binding site is easily affected by
2+ 22
2+
Cu . Fig. 7 shows that, upon addition of Cu , the proton (amide
NH ) signal at δ 11.7 ppm completely disappeared. This result
a
2+
indicates the influence of Cu on the amide NH group. In addition,
Fig.
6 Geometry-optimized (PBE0/LANL2DZ) structures of L1 with
2+
the proton H (CH=N) also disappeared at about δ = 9.55 ppm.
Furthermore, Cu addition leads to a large downfield shift of 0.5
b
complex Cu ion. Left: The free ligand L1 (Ellipsoid); Right: Ligand L1
2+
2+
complex with Cu ion (Ellipsoid). Colour code: carbon = dark grey and
oxygen atom = red, nitrogen = blue and Cu = purple.
2+
Fig. 5 Fluorescence response of L1 (1.0 ꢀM) in CH
3
CN/CH
2 2
Cl (1000:1, v/v)
to 10.0 ꢀM of various tested metal ions and to the mixture of 10.0 ꢀM of
2+
tested metal ions with 10.0 ꢀM Cu ion. Here L represents the emission
2
+
1
intensity of ligand L1 in the presence of Cu . I
of free L1, and I is the fluorescence intensity after addition of metal ions at
05 nm.
0
is the fluorescence intensity
Fig. 7 Partial H-NMR titration of L1/guest (H/G = 1:1); (a) Free ligand L1
–
3
2+
2+
(8.60 × 10 M); (b) L1⊃ Cu (0.5 equiv.) (c) L1⊃ Cu (1 equiv.); (d)
2+
4
3
L1⊃ Cu (2 equiv.). Solvent: CDCl –DMSO (9:3, v/v). 400 MHz at 298 K.

6
Tetrahedron
ACCEPTED MANUSCRIPT
1
2+
Table 2. H NMR chemical shift differences of free L1 and L2 with L1⊃ Cu
and L2⊃ Cu , respectively.
2+
a
δppm in L1 (H/G = 1:1)
δppm in L2 (H/G = 1:1)
2+
2+
Free L1 L1⊃ Cu
∆δ
----
Free L2 L2⊃ Cu
∆δ
Ha
Hb
Hc
Hd
He
11.66
9.55
7.06
8.74
4.81
----
----
11.79
9.58
7.04
8.77
3.92
----
----
----
----
----
7.56
9.28
4.75
0.50
0.54
0.05
7.21
8.96
3.91
0.16
0.26
0.01
a
ꢁ
δ Values are the difference of the chemical shift between free ligand L1 or
2+
Fig. 8 Geometry-optimized (PBE0/LANL2DZ) structures (Space fill) of L1
2+ 2+
L2 and complexation with Cu .
and as its Cu complex ion. Left: The free ligand L1; Right: 1:1 L1⊃ Cu
complex. Colour code: carbon = drack grey and oxygen atom = red, nitrogen
(Figure SI 15). The diethylaminocarbonylmethoxy, carbonyl carbon
2+
=
blue and Cu = purple.
C1, and the hydrazido carbonyl carbon C2, of L1 were first
2+
identified by comparison with L2. Upon the addition of Cu , the C2
and C3 peaks of the ligand L1 disappeared completely and the
resonances corresponding to the C1 carbon mostly disappeared. H
3
. Conclusion
1
In conclusion, fluorogenic molecules L1, L2 and L3 which are
pyrene-based Schiff base derivatives have been designed in order to
NMR analysis revealed that the changes are almost terminated after
2+
2+
compare their binding affinities for Cu detection where the probes
worked as a fluorescence “turn off-on” sensor. A PET mechanism
was exploited to afford a convenient analytical strategy. The sensing
ability and photophysical properties are well-supported by the
fluorescence spectra and NMR titration experiments. The
hydrazidocarbonyl moiety L1 and L2, are strongly co-ordinated with
addition of 1.0 molar equiv. of Cu which is indicative of a 1:1
binding complex formation. It is also proposed that ligand L1 forms
2
+
a
complex with Cu
by strong coordination with the
2+
hydrazidocarbonyl moiety. In this case, Cu is coordinated with the
imine nitrogen atom and amide carbonyl oxygen of ligand L1.
Furthermore, the diethylaminocarbonylmethoxy group also has a
2+
2+
Cu . Moreover, the upper part of L1 has a noticeable effect upon the
prominent influence through an inductive effect on the L1⊃ Cu
2+
binding of the complex of L1⊃ Cu which is also supported by DFT
computational studies. Consequently, receptor L1 acquires a higher
affinity (65-fold enhanced) in comparison with compound L2 (25-
fold) and L3 exhibits very weak fluorescence enhancements (7-fold)
complexation.
A DFT computational study was also undertaken to shed further
2+
light on the binding mode of the ligand with Cu . The geometries of
the molecular structures were optimized with the PBE0 functional
with the LANL2DZ basis set. The DFT level of theory using the
hybrid Perdew-Burke-Ernzerhof parameter free-exchange correlation
2+
for Cu detection.
4
. Experimental
.1. General
27
functional PBE0 (PBE1PBE in the Gaussian realization) with the
Hay and Wadt effective core potential LANL2DZ basis set was
4
28
employed. The starting structure was first generated using
1
13
H and C NMR spectra were recorded on a Nippon Denshi JEOL
29
SpartanPro10 with the MMFF94 method. The generated structures
FT-300 NMR spectrometer and Varian-400MR-vnmrs400 with
SiMe4 as an internal reference: J-values are given in Hz. IR spectra
were measured for samples as KBr pellets in a Shimadzu FTIR-8400
spectrophotometer. Mass spectra were obtained with a Nippon
Denshi JMS-HX110A Ultrahigh Performance Mass Spectrometer at
30
were then imported into Gaussian-09 Revision D.01 and were
geometry-optimized in the gas-phase. The calculated
interactionenergy (IE) for each of L1⊃ Cu and L2⊃ Cu are -
2+
2+
–
1
1
519.2 and -1467.8 kJ mole , respectively (See SI section for
2+
details). The DFT binding mode of the guest Cu ion involves
strong coordination with the hydrazidocarbonyl moiety of the ligands
L1 and L2. Furthermore, from the computed IE data, L1⊃ Cu is
7
5 eV using a direct-inlet system. Elemental analyses were
performed by a Yanaco MT-5. UV-vis spectra were recorded using a
Shimadzu UV-3150UV-vis-NIR spectrophotometer. Fluorescence
spectroscopic studies of compounds in solution were performed in a
semimicro fluorescence cell (Hellma®, 104F-QS, 10 × 4 mm, 1400
2+
–1
energetically favoured by 50.2 kJ mole over the corresponding
2+
L2⊃ Cu complex, which is in agreement with the trend for the
observed complexation data obtained by fluorescence titration
experiments. This finding is also in agreement with the observed
changes in the chemical shifts of the surrounding
hydrazidocarbonyl moiety of both ligands and the changes of
the chemical shifts of the upper part of ligand L1. The interaction
energy (IE) for each complex was calculated according to equation
ꢀ
L) with a Varian Cary Eclipse spectrophotometer. Fluorescence
quantum yields were recorded in solution (Hamamatsu Photonics K.
K. Quantaurus-QY A10094) using the integrated sphere absolute PL
quantum yield measurement method. Unless otherwise stated, all
reagents used were purchased from commercial sources and were
used without further purification. All the solvents used were dried
and distilled by the usual procedures before use. All melting points
(Yanagimoto MP-S1) are uncorrected.
(1):
2+
IE = EComplex − Σ(Eligand + ECu ion)
(1)

Løvstad, BioMetals. 2004, 17, 111–113.
4
.2. Materials
ACCEPTED MANUSCRIPT
6
.
(a) G. D. Barceloux, and D. D Barceloux, J. Toxicol.-Clin. Toxicol., 1999,
7, 217–230; (b) X. B. Zhang, J. Peng, G. L. Shen and R. Q. Yu, Anal.
3
4
.2.1. Synthesis of Compound 2. To 1 (300 mg, 1.19 mmol) in a
Chim. Acta. 2006, 567, 189-195; (c) L. E. Que, W. D. Domaille and C.
Chang, Chem. Rev. 2008, 108, 1517–1549.
round-bottom flask, ethanol (18 mL) and hydrazine hydrate (3.0 mL)
were added and with stirring, the temperature was maintained at 60
7
.
(a) Y. Zheng, K. M. Gattas-Asfura, V. Konka and R. M. Leblanc, Chem.
Commun. 2002, 20, 2350–2351; (b) L. Zeng, E. W. Miller, A. Pralle, E. Y.
Isacoff and C. J. Chang, J. Am. Chem. Soc. 2006, 128, 10–11; (c) X. Qi, E.
J. Jun, L. Xu, S. Kim, J. S. J. Hong, Y. J. Yoon and J. Yoon, J. Org. Chem.
2006, 71, 2881–2884; (d) J. Liu and Y. Lu, J. Am. Chem. Soc. 2007, 129,
9838–9839; (e) S. Wu, R. Huang and K. Du, Dalton Trans. 2009, 24,
4735–4740; (f) S. Wu and S. Liu, Sens. Actuators. B. 2009, 141, 187–191.
(a) E. Kimura, S. Aoki, E. Kikuta and T. Koike, Proc. Natl. Acad. Sci. U.
S. A. 2003, 100, 3731-3736; (b) Y. Mikata, M. Wakamatsu and S. Yano,
Dalton Trans. 2005, 3, 545–550; (c) K. Komatsu, Y. Urano, H. Kojima
and T. Nagano, J. Am. Chem. Soc. 2007, 129, 13447–13454; (d) X. Chen,
J. Shi, Y. Li, F. Wang, X. Wu, Q. Guo and L. Liu, Org. Lett. 2009, 11,
°
C for 30 h. The reaction mixture was cooled to room temperature
and concentrated under reduced pressure to afford a colourless solid.
Crystallization from a mixture of CH Cl –CH OH (2:1, v/v) afforded
2
2
3
compound 2 as colourless prisms (240 mg, 76%). Mp: 157.5 °C; IR:
νmax(KBr) = 3294 (NH ) and 1635 (C=O) cm . H NMR (300 MHz,
CDCl3):
NH), 4.72 (2H, s, CH O), 6.97 (2H, d, J = 8.22 Hz, Ar-H), 7.54 (2H,
s, NH ) and 7.72 (2H, d, J = 8.22 Hz, Ar-H) ppm. C NMR (100
MHz, CDCl3):
1
−1 1
2
8
.
.
δ = 1.17 (6H, m, CH ), 3.38 (4H, m, CH ), 4.07 (1H, s,
3 2
2
13
2
δ = 12.8 (CH ), 40.4 (CH ), 67.2 (CH ), 114.2 (Ar-C),
3 2 2
4
426–4429; (e) L. Xue, C. Liu and H. Jiang, Chem. Commun. 2009, 9,
25.7 (Ar-C), 128.7 (Ar-C), 160.9 (Ar-C), 166.3 (C=O) and 168.1
1061–1063.
+
9
1
H. Irving and R. J. P. Williams, J. Chem. Soc. 1953, 3192–3210.
(
C=O) ppm. FABMS: m/z 266.16 [M ]. Anal. calcd. for C H N O :
13 19 3 3
0. (a) C. Y. Lai, B. G. Trewyn, D. M. Jeftinija, K. Jeftinija, S. Su, S.
Jeftinija and S. Y. V. Lin, J. Am.Chem. Soc. 2003, 125, 4451–4459; (b)
M. Numata, C. Li, A. H. Bae, K. Kaneko, K. Sakurai and S. Shinkai,
Chem. Commun. 2005, 37, 4655–4657.
1. (a) P. A. de Silva, N. Q. H. Gunaratne, A. T. Gunnlaugsson, M. T. Huxley,
P. C. McCoy, T. J. Rademacher and E. T. Rice, Chem. Rev. 1997, 97,
C, 58.84; H, 7.22; N, 15.84. Found: C, 59.17; H, 7.16; N, 15.76.
.2.2. Synthesis of Receptor L1. A solution of 1-pyrenecarbaldehyde
40 mg, 0.15 mmol) in methanol (5.0 mL) was added to a solution of
(39 mg, 0.17 mmol) in a 1:1 mixture of chloroform and methanol
20 mL). The mixture was heated at reflux for 24 h and concentrated
4
(
2
(
1
1
2
1
515–1567; (b) F. J. Callan, P. A. de Silva and C. D. Magri, Tetrahedron.
005, 61, 8551–8588; (c) S. J. Kim and T. D. Quang, Chem. Rev, 2007,
07, 3780–3799; (d) B. Liu and H. Tian, Chem. Commun. 2005, 25,
under reduced pressure, to afford a yellow solid. Crystallization from
a mixture of chloroform–methanol (3:1, v/v) afforded compound L1
as a light yellow solid (50 mg, 69%). Mp: 253.5 °C. IR: νmax(KBr) =
3156–3158; (e) X. Qi, J. E. Jun, L. Xu, J. S. Kim, J. S. J. Hong and J. Y.
Yoon, J. Org. Chem. 2006, 71, 2881–2884; (f) H. S. Kim, J. S. Kim, M.
S. Park and K. S. Chang, Org. Lett. 2006, 8, 371–374; (g) S. H. Jung, S.
P. Kwon, W. J. Lee, I. J. Kim, S. C. Hong, W. J. Kim, S. Yan, Y. J. Lee,
H. J. Lee, T. Joo and S. J. Kim, J. Am. Chem. Soc. 2009, 131, 2008–2012;
−1
1
1
650 (CH=N and C=O), 3256 (NH) cm . H NMR (400 MHz,
CDCl / DMSO = 9:3): δ = 1.03 (6H, m, CH ), 3.20 (4H, m, CH ),
3
3
2
(
2
h) X. Huang, Z. Guo, W. Zhu, Y. Xie and H. Tian, Chem. Commun.
008, 77, 5143–5145.
2. (a) V. Dujols, F. Ford and W. A. Czarnik, J. Am. Chem. Soc. 1997, 119,
386–7387; (b) J. Liu and Y. Lu, J. Am. Chem. Soc. 2007, 129, 9838–
4
.70 (2H, s, OCH ), 6.93 (2H, d, J = 8 Hz, Ar-H), 7.99 (2H, d, J = 8
2
Hz, Ar-H), 8.61 (1H, d, J = 12 Hz, Py-H), 7.91–8.23 (8H, m, Py-H),
9
MHz, CDCl /DMSO = 9:3): δ = 13.6 (CH ), 41.0 (CH ), 67.1 (CH ),
1
and 166.3 (C=O) ppm. FABMS: m/z 478.21 [M ]. Anal. calcd. for
C H O N : C, 75.45; H, 5.70; N, 8.80. Found: C, 75.26; H, 5.31; N,
8
1
1
13
.44 (1H, s, HC=N) and 11.55 (1H, s, NH) ppm. C NMR (100
7
9839; (c) K. W. K. Swamy, K. S. Ko, H. Lee, C. Mao, M. J. Kim, H. K.
Lee, J. Kim, I. Shin and J. Yoon, Chem. Commun. 2008, 45, 5915–5917;
3
3
2
2
14.6−132.7 (Ar-C, Py-C), 146.7 (C=N), 161.2 (Ar-C), 163.9 (C=O)
(d) X. Chen, M. Jou, H. Lee, S. Kou, J. Lim, W. S. Nam, S. Park, M. -K.
+
Kim and J. Yoon, Sens and Actuators B. 2009, 137, 597–602; (e) Z. C.
Wen, R. Yang, H. He and Y. B. Jiang, Chem. Commun. 2006, 42, 106–
30
27
3
3
1
08.
3. (a) V. A. Varnes, B. R. Dodson and L. E. Whery, J. Am. Chem. Soc.
972, 94, 946–950; (b) A. J. Kemlo and M. T. Shepherd, Chem. Phys.
.57%.
1
Acknowledgments
Lett. 1977, 47, 158–162; (c) K. Rurack, U. Resch, M. Sensoer and S.
Daehne, J Fluoresc. 1993, 3, 141–143.
This work was performed under the Cooperative Research
Program of “Network Joint Research Center for Materials and
Devices (Institute for Materials Chemistry and Engineering, Kyushu
University)”. We would like to thank the OTEC at Saga University
and the International Collaborative Project Fund of Guizhou
province at Guizhou University for financial support. CR thanks the
EPSRC for a travel grant. The computational work has been assisted
by the use of computing resources provided by WestGrid and
Compute/Calcul Canada for which Dr. Grigory Shamov's assistance
is thanked.
1
1
1
1
4. K. Li, N. Li, X. Chen and A. Tong, Anal. Chim. Acta. 2012, 712, 115–
1
19.
5. K. Rurack, U. Resch-Genger and W. Rettig, J. Photochem. Photobiol. A.
Chem. 1998, 118, 143–149.
6. Y. Zhou, F, Wang, Y. Kim, J. S. Kim and J. Yoon, Org. Lett. 2009, 11,
4
442–4445;
7. (a) K. Hanaoka, Y. Muramatsu, Y. Urano, T. Terai and T. Nagano,
Chem.–Eur. J. 2010, 16, 568–572; (b) Y. Chen, C. Zhu, Z. Yang, J. Li,
Y. Chiao, W. He, J. Chen and Z. Guo, Chem. Commun. 2012, 48, 5094–
5
2
096; (c) J. Wu, W. Liu, J. Ge, H. Zhang and P. Wang, Chem. Soc. Rev.
011, 40, 3483–3495; (d) J. Zhao, S. Ji, Y. Chen, H. Guo and P. Yang,
Phys. Chem. Chem. Phys. 2012, 14, 8803; (e) J. B. Birks, M. D. Lumb, I.
H. Munro, Proc. R. Soc. London 1964, A280, 289; (f) I. Takashima, M.
Kinoshita, R. Kawagoe, S. Nakagawa, M. Sugimoto, I. Hamachi and A.
Ojida, Chem.−Eur. J. 2014, 20, 2184−2192.
Supplementary data
Electronic Supplementary Information (ESI) available: Details of
the NMR spectra and titration experimental data. See
DOI: 10.1039/b000000x/
18. (a) M. F. Winnik, Chem. Rev. 1993, 93, 587–614; (b) C. Yao, B. H.
Kraatz and P. R. Steer, Photochem. Photobiol. Sci. 2005, 4, 191−199; (c)
B. J. Birks, Rep. Prog. Phys. 1975, 38, 903−974.
1
9. (a) E. Manandhar and J. K. Wallace, Inorg. Chim. Acta. 2012, 381,
5−43; (b) S. Karuppannan and C. J. Chambron, Chem. Asian J. 2011, 6,
1
References and Notes
964−984; (c) Y. Zhou, C. Zhu, S. X. Gao, Y. X. You and C. Yao, Org.
Lett. 2010, 12, 2566−2569; (d) R. Martínez, A. Espinosa, A. Tárraga and
P. Molina, Tetrahedron. 2010, 66, 3662−3667; (e) V. Chandrasekhar and
D. M. Pandey, Tetrahedron Lett. 2011, 52, 1938−1941; (f) L. X. Ni, S.
Wang, X. Zeng, Z. Tao and T. Yamato, Org. Lett. 2011, 13, 552−555; (g)
H. S. Jung, M. Park, D. Y. Han, E. Kim, C. Lee, S. Ham and J. S. Kim,
Org. Lett. 2009, 11, 3378−3381.
1
.
X. Li, X. Gao, W. Shi and H. Ma, Chem. Rev. 2014, 114, 590–659.
K. P. Carter, A. M. Young and A. E. Palmer, Chem. Rev., 2014, 114,
2
3
4
5
.
.
.
.
4
564–4601.
M. Formica, V. Fusi, L. Giorgi and M. Micheloni, Coord. Chem. Rev.
012, 256, 170–192.
2
J. S. Lippard and M. J. Berg, Principles of Bioinorganic Chemistry;
University Science Books: Mill Valley, CA, 1994.
20. Y. S. Wu, C. Y. Li, Y. F. Li, D. Li and Z. Li, Sens. Actuators B: Chem.
2016, 222, 1226–1232.
21. P. Venkatesan and S. P. Wu, RSC Adv. 2015, 5, 42591–42596.
(a) G. Muthup, A. Schlicksupp, L. Hess, D. Beher, T. Ruppert, C. L.
Masters and K. Beyreuther, Science. 1996, 271, 1406–1409; (b) A. R.

8
Tetrahedron
ACCEPTED MANUSCRIPT
2
2. S. P. Wu, Z. M. Huang, S. R. Liu and P. K. Chung, J Fluoresc. 2012, 22,
2
53–259.
2
2
2
3. Nagaraju and S. Pal, J. Organomet. Chem. 2013, 737, 7–11.
4. P. S. Lee and N. Yoshikai, Angew. Chem. 2013, 52, 1240–1242.
5. (a) P. Thordarson., Chem. Soc. Rev. 2011, 40, 1305–1323; (b)
http://supramolecular.org; (c) H. A. Benesi and J. H. Hildebrand, J. Am.
Chem. Soc. 1949, 71, 2703–2707.
2
2
2
2
3
6. (a) S. Goswami, A. K. Das and S. Maity, Dalton Trans. 2013, 42,
1
6259−16263; (b) L. Porrès, A. Holland, L.-O. Pålsson, A. P. Monkman,
C. Kemp and A. Beeby, J Fluoresc. 2006, 16, 267–272.
7. (a) J. P. Perdew, K. Burke and Ernzerhof, M. Phys. Rev. Let. 1996, 77,
3
1
865–3868; (b) J. P. Perdew, K. Burke and Ernzerhof, M. Phys. Rev. Let.
997, 78, 1396.
8. (a) P. J. Hay and W. R. Wadt, J. Chem. Phys. 1985, 82, 270; (b) P. J.
Hay, W. R. Wadt, J. Chem. Phys. 1985, 82, 284; (c) P. J. Hay and W. R.
Wadt, J. Chem. Phys. 1985, 82, 299.
9. Initial molecular modeling calculations using the MMFF94 method were
performed using the PC Spartan'10 software from Wavefunction Inc.,
Irvine CA.M.
0. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb,
J. R.Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson,
H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J.
Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R.
Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H.
Nakai, Jr. T. Vreven, J. A. Montgomery, J. E. Peralta, F. Ogliaro, M.
Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, T.
Keith, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C.
Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M.
Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R.
Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C.
Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski,
G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, O.
Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski and D. J. Fox,
Gaussian 09, Revision D.01; Gaussian, Inc., Wallingford CT, 2013.