Spectroscopic investigation of bis-appended 1,2,3-triazole probe for the detection of Cu(II) ion

Article abstract of DOI:10.1016/j.molstruc.2016.12.096

A novel bis-1,4-disubstituted-1,2,3-triazole chemosensor, accessed with “Click Chemistry”, was probed for its recognition of metal ions. The interaction of the sensor with various cation analytes was investigated by ¹H-NMR, UV–Vis absorption an

Full text of DOI:10.1016/j.molstruc.2016.12.096

Accepted Manuscript
Spectroscopic investigation of bis-appended 1,2,3-triazole probe for the detection of
Cu(II) ion
Debanjana Ghosh, Shannon Rhodes, Domonique Winder, Austin Atkinson, Jaclyn
Gibson, Weihua Ming, Clifford Padgett, Shainaz Landge, Karelle Aiken
PII:
S0022-2860(16)31415-6
10.1016/j.molstruc.2016.12.096
MOLSTR 23294
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 2 September 2016
Revised Date: 13 December 2016
Accepted Date: 28 December 2016
Please cite this article as: D. Ghosh, S. Rhodes, D. Winder, A. Atkinson, J. Gibson, W. Ming, C. Padgett,
S. Landge, K. Aiken, Spectroscopic investigation of bis-appended 1,2,3-triazole probe for the detection
of Cu(II) ion, Journal of Molecular Structure (2017), doi: 10.1016/j.molstruc.2016.12.096.
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ACCEPTED MANUSCRIPT
Spectroscopic Investigation of Bis-Appended 1,2,3-Triazole Probe for the Detection of Cu(II) Ion
a
a
a
a
a
a
b
Debanjana Ghosh , Shannon Rhodes , Domonique Winder , Austin Atkinson , Jaclyn Gibson , Weihua Ming , Clifford Padgett ,
a
a
Shainaz Landge *, Karelle Aiken *
Abstract: A novel bis-1,4-disubstituted-1,2,3-triazole chemosensor, accessed with “Click Chemistry”, was probed for its
1
recognition of metal ions. The interaction of the sensor with various cation analytes was investigated by H-NMR, UV-Vis
absorption and fluorescence spectroscopy. The bis-triazole is selective for Cu(II) with a detection limit in the micromolar-
concentration range and a clear to yellow colorimetric response that is exclusive to that ion is observed. The stoichiometry of
1
probe to Cu(II), 2 : 1, was determined with Job’s plots based on titration studies using UV-absorption and H-NMR spectroscopy.
Computational and spectroscopic investigations revealed that the sensor binds to Cu(II) via its triazole units.
Keywords:
bis-triazole,
copper(II),
chemosensor,
click
chemistry
1
. Introduction:
Considerable attention has been given to the rational
biological significance, it is important to develop sensors that are
truly exclusive to one particular ion. Additionally, copper ions with
their fluorescent-quenching properties makes the design of
design of small organic chemonsensors for metal ions, particularly
heavy transition metals (HTMs). Structurally, ion sensing in these
probes can occur through displacement reactions,(1) metal-promoted
bond formation and cleavage,(2) and metal-chelator complexes.(3)
With the metal-chelator complexes, the potential exists to “tune” the
selectivity and sensitivity of the probes by (i) taking advantage of
cation affinity for specific atoms and (ii) controlling the size of the
binding site through the intentional placement of the coordinating
moieties in the sensors.(3) In most cases, a chelate arises from
covalent or coordinate bonds between the metal and donor-
functional groups containing sulfur, nitrogen and/ or oxygen
atoms.(4)
molecules that provide
attractive.(21-23)
a
“turn-on” colorimetric responses
1
,2,3-Triazoles have emerged as promising chelators for
HTMs because they can act as nitrogen (N)-donors.(24-26) Many
,2,3-triazole metal complexes have been probed for their suitability
1
in metallo-supramolecular systems.(27) In general, triazole
2
structures use their nitrogens to bind cations, and their Csp -H
proton to bind the anions.(27, 28) The triazo- ligands are often made
using the Click reaction, 1,3-dipolar Cu(I) catalyzed alkyne-azide
cycloaddition (CuAAC), which is a simple, high yielding and atom
economical process.(29) Previous work with bis-triazoles has
targeted cation sensing, particularly HTMs.(11, 30-42) A number of
studies have employed a “turn-off” response, taking advantage of
Metal cations are of biological and ecological
importance.(5-7) Copper, in particular, is the third most abundant
heavy metal in the body. This metal has an average concentration of
2
+
+
2+
fluorescence quenching properties of metals such as Ni , Ag , Pb ,
2+
2+
2+
-
1
Hg and of course, Cu .(30-34, 37, 39-41) With respect to Cu
,
1
00-150 ꢀg L in the blood under normal conditions(8) and it serves
there are less reports for bis-triazole sensors that provide a
colorimetric signal.(43) Additionally, in many instances the bis-
triazole sensors fail to respond exclusively to Cu(II).(31, 34, 37, 38)
as a co-factor for many proteins and enzymes.(9, 10) As a result,
copper is essential for important processes such as proper brain
function;(11) the stabilization of collagen fibrils and increased
elasticity of elastin;(12, 13) the maintenance of the natural,
intracellular homeostasis of iron;(14) ATP biosynthesis;(15) and the
production of melanin in the skin.(16, 17) Therefore, an under- or
over-supply of copper can be harmful. For example, intracellular
copper-deficiency causes Menkes syndrome while an overload of
copper is implicated in Wilson’s disease.(18) Both can be fatal.
Herein, we report the synthesis of a novel bis-1,2,3-
triazole sensor appended with phenolic groups, (2,2-bis((1-(2-
hydroxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)-5,5-
dimethylcyclohexane-1,3-dione) (BPT) (Scheme 1). BPT exhibits a
selective colorimetric response to copper(II), clear to yellow. To
verify the selectivity, BPT was screened against an series of metal
3
+
2+
2+
+
3+
3+
2+
2+
2+
2+
2+
Additionally, copper has
neurodegenerative diseases such as Alzheimer’s, Parkinson’s and
Prion’s Diseases.(18-20) In these cases, copper is involved in plaque
a
role in the progression of
ions (Fe , Fe , Cu , Ag , Cr , Al , Co , Ni , Cd , Zn , Mg ,
+
Li ). Spectroscopic investigations with Nuclear Magnetic Resonance
Spectroscopy (NMR), UV-absorption and fluorescence spectroscopy
formation and the production of harmful reactive oxygen species quantified the molecule’s response to each cation. Additionally,
(
ROS). In light of the fact that copper is significant to many
computational studies along with NMR titration investigations were
used to determine the Cu(II) binding site in BPT. Overall, our results
reveal the existence of a 2 : 1 metal coordination complex for BPT :
Cu and provide insight into the structural characteristics of BPT
that are important for metal-chelation.
biological processes, selective and sensitive copper-chemosensors
can greatly impact human health. For example, these sensors could
be used for diagnostic purposes, to enhance understanding of the
metal’s role in various diseases, in the development of more
effective treatments and to track copper ion levels in the
environment.
2+
2
. Experimental:
2
.1 Materials and methods
Many challenges still exist in designing effective copper
sensors. Like all metals, especially those of environmental and

All chemicals and reactants including
for BPT synthesis and the perchlorate salts of metal ions were
A
the
C
st
C
ar
E
tin
P
g
T
ma
E
te
D
rialMAM.
N
P.
U
23
S
0.8
C
–
R
23
I
4
P
.0
T
°C.
1
H NMR (400 MHz, (CD ) SO) δ 10.53 (broad s, OH), 8.15 (s, 2-
3
2
obtained from commercially available sources and used without H), 7.58 (dd, 2-H, 1.6, 7.9 Hz), 7.31 (td, 2-H, 1.6, 7.8 Hz), 7.09 (dd,
further purification. Column Chromatography was performed with 2-H, 0.94, 8.2 Hz), 6.96 (td, 2-H, 1.0, 7.8 Hz), 3.29 (s, 4-H), 2.77 (s,
Selecto Scientific Si-gel (particle size 100-200 microns). Melting 4-H), 0.89 (s, 6-H).
13
points were measured with Vernier Melt Station using Vernier
C NMR (101 MHz, (CD ) SO) δ 208.1, 149.6, 142.1, 130.2,
3 2
LabQuest 2 and are uncorrected. High Resolution MS (HRMS) 125.6, 125.1, 124.9, 119.9, 117.5, 68.5, 51.2, 30.9, 30.2, 28.8.
+
analyses were performed using MALDI, Q-TOF micro, 3200API, HRMS (M + H) for C H N O : calculated = 487.2075, found =
26
27
6
4
LCMS, GCMS EI (DI).
NMR spectra were recorded on Agilent MR400DD2
spectrometer, with a multinuclear probe with two RF channels and
487.2061. (see ESI,† Fig. S11)
1
1
N3
OH
2
5
3
4
1
13
Br
O
O
8
1
5
variable temperature capability: H-NMR: 400 MHz and C-NMR:
00 MHz. The NMR solvent, DMSO-D6 ((CD ) SO), was
O
O
6
7
HO
9
OH
O
O
K
2
CO
3
CuSO .
5H
O,
14
4
2
13
1
3
2
N
N
N
Sodium ascorbate,
t-BuOH/H O, reflux
N
N
N
12
purchased from Acros Organics. The reference was set for residual
2
10
1
1
1
13
(
CH ) SO at 2.50 ppm for H-NMR and 30.37 ppm for C-NMR.
BPT
3
2
The NMR signals were reported in parts per million (ppm) relative to
Scheme 1. Synthesis of probe BPT (2,2-bis((1-(2-hydroxyphenyl)-
the residual solvent and were described with multiplicity, singlet (s), 1H-1,2,3-triazol-4-yl)methyl)-5,5-dimethylcyclohexane-1,3-dione)
doublet (d), triplet (t), triplet of doublet (td), quartet (q) and multiplet (BPT).
(
m); coupling constants (J; Hz) and integration.
Room temperature absorption and steady state
3
. Results and Discussion:
BPT was subjected to single crystal X-ray analysis. The
fluorescence measurements were performed using a Shimadzu UV-
450 spectrophotometer and PerkinElmer LS55 with well plate
reader fluorimeter respectively. The concentration of BPT was kept sensor and its interaction with various metal ions were fully
2
-
5
-3
at ~2.0 × 10 mol dm in methanol to avoid any possible characterized with NMR (1D and 2D), UV-Vis absorption, and
intermolecular effect. For the experiment in water, methanol has fluorescence
spectroscopy. Complimentary computational
been used as a co-solvent in aqueous bulk. BPT in aqueous solution experiments were undertaken to verify the structural properties of
2+
was prepared by adding BPT (methanol) to water in the ratio of 1:60 the probe that are important in Cu detection.
-
3
-3
(
v/v). Individual stock concentrations of ~5.0 × 10 mol dm for the
3
.1 X-ray Structure Determination
BPT crystallized in the orthorhombic space group P2 2 2
1 1
perchlorate salts of metal ions were also prepared in methanol and
deionized (D. I.) water. The methanol was HPLC grade. All the
experiments are performed at ambient temperature (27 °C) with air-
equilibrated solutions.
1
(
#19) with the unit cell parameters a = 7.3216(6) Å, b = 12.0506(9)
Å and c = 27.584(3) Å (Table 1, see ESI,† Tables 1-3 and Figs. S12-
4). The structure was collected at 173 K and had an unweighted r
1
A colourless crystal of BPT having the approximate factor of 4.35% (R ). Figure 1 shows the single-crystal structure of
1
dimensions of 0.2 mm × 0.2 mm × 0.2 mm was obtained by slow BPT. The structure is held together to two independent hydrogen
evaporation of DMSO and mounted on a glass fiber. All bonding chains with H-bonds between the phenolic O-H and triazole
measurements were made on a Rigaku XtaLAB mini diffractometer nitrogen of neighboring molecules. The first chain runs parallel to
using graphite monochromatic Mo-K radiation at low temperature the a-axis, the second runs parallel to the b-axis (Figs. 2 & 3).
α
(-100 °C).
Combined, these form a network of hydrogen bonds that hold the
structure together.
2
.2 General procedure for synthesis of BPT (Scheme 1)
Table 1. Crystallographic Data for BPT
2
-Azidophenol(44) (718 mg, 5.32 mmol) and 5,5-dimethyl-2,2-
Compounds
Empirical formula
Formula weight
Temperature (K)
Crystal system
Space Group
a (Å)
BPT
bis(2-propynyl)-1,3-cyclohexanedione(45) (501 mg, 2.31 mmol)
were suspended in tert-butanol/water (53 mL; 1:1, v/v) in a round
bottomed flask. The reaction was then heated for 15-20 min to allow
the reactants to fully dissolve. An aqueous solution of copper(II)
sulfate pentahydrate (57.7 mg, 0.23 mmol in 5.0 mL of water) was
added dropwise, followed by sodium ascorbate (463 mg, 2.31
mmol). The reaction was vigorously stirred while refluxing for 18
hours. Upon cooling to room temperature, the resulting mixture was
placed in an ice bath and diluted with cold D. I. water (~50 mL) to
induce precipitation. The crude, solid product was collected with
vacuum filtration and subjected to thorough washing with D. I. water
followed by ethyl acetate to yield an off-white/beige powder, 390
mg (33%).
C H N O
4
26
26
6
486.53
173
Orthorhombic
P2 2 2
1
1 1
7.3216 (6)
12.0506 (9)
27.584 (3)
90
b (Å)
c (Å)
α (°)
β (°)
90
γ (°)
90
3
Volume (Å )
2433.7 (4)
2

Z
A
4
CCEPTED MA3.2
N
N
U
MR
S
S
C
tu
R
di
I
e
P
s
T
-
3
Dcal (g cm )
1.328
0.09
The binding behavior of BPT was explored with various
-
1
ꢀ
(mm )
cations via NMR spectroscopy in deuterated DMSO (DMSO-D6).
The H NMR spectrum of BPT (see ESI,† Fig. S1) showed the
F (000)
1024.0
1
3
Crystal Size (mm )
0.20 × 0.20 × 0.20
2.8-27.50
2
distinctive triazole Csp –H singlet at 8.15 ppm. This singlet is easily
distinguished from other signals in the aromatic region. For that
θ Range for data collection (°)
2
-
9 ≤ h ≤ 9
particular reason, changes in the triazole Csp -H peak position upon
Index ranges
-15 ≤ k ≤ 15
addition of analytes has been exploited in many applications(46-48)
and in our studies as well.(28) The phenolic -OH appears in the
region of δ 10.53 ppm as a broadened singlet. The rest of the
aromatic region from δ 6.94 – 7.59 ppm and the aliphatic protons
from δ 0.80 – 3.40 ppm show the expected coupling patterns. The
-
35 ≤ l ≤ 35
26,095
0/325
Reflections Collected
Restraints / parameters
2
Goodness-of-fit on F
1.10
13
Final R indexes [I > 2σ(I)]
R = 0.044 wR = 0.100
C NMR experiments for BPT (see ESI,† Fig. S2) gave the signals
1
2
Final R indexes [all data]
R = 0.0543 wR = 0.100
in the anticipated regions; the aliphatic ranging from δ 28.8 – 68.5
ppm and the aromatic from δ 117.5 – 150.0 ppm. The carbonyls of
cyclohexanedione resonate at 208.1 ppm. COSY and HSQC
experiments were used to assist with making full assignments for
proton and carbon signals, respectively (see ESI,† Fig. S3, S4a and
1
2
−3
Largest diff. peak and hole (e Å )
0.17 and −0.23
1
1
13
S4b). It should be noted that H and C NMR spectra for BPT in
deuterated methanol are similar to those with DMSO-D6.
1
2
4
3
The Nuclear Overhauser Effect (NOE) experiments were
carried out to determine the conformation of BPT in solution before
chelation (see ESI,† Fig. S5). More specifically, investigations
1
5
5
1
4
1
3
8
7
2
probed a possible correlation between the triazole Csp –H and
6
1
2
2
phenolic Csp -H ortho to the axial bond. In our previous work with
9
PTP (2-(4-phenyl-1-H-1,2,3-triazol-1-yl) phenol), a mono-triazole
sensor, it was clearly indicated that the triazole proton was in close
proximity to that region (Fig. 4).(28) However, with the present bis-
triazole appended derivative we did not observe any interaction (Fig.
1
0
1
1
Figure 1: A displacement ellipsoid plot for BPT (50% probability;
2
hydrogen atoms removed for clarity).
4). In the single X-ray crystal structure for BPT the triazole Csp –H
proton is on the same side as the phenolic oxygen (Fig. 1). It is likely
that the molecule retains this conformation in solution as well.
(A)
NOE
H
H
HO
H
N
N
N
N
N
N
H
HO
PTP
Figure 2: A single of layer of the unit cell viewed down the c-axis
highlighting the hydrogen bonding motif that runs parallel to the a-
axis.
observed
(B)
NOE
O
O
O
O
H
H
H
H
H
OH
HO
H
N
N
N
N
N N N
N
N
N
N
N
H
OH
HO
H
not observed
BPT
Figure 4. NOESY correlation for (A): PTP(28) and (B): BPT
Figure 3: A single of layer of the unit cell viewed down the a-axis
highlighting the hydrogen bonding motif that runs parallel to the b-
axis.
To gain insight into BPT’s interaction with copper(II) and
1
other ions, H NMR experiments were conducted with selected
2+
2+
2+
+
3+
2+
2+
cations (Zn , Cu , Fe , Ag , Al , Co , Ni ) (Fig. 5). The sensor,
3

in deuterated dimethyl sulfoxide, was treate
A
d
C
w
C
ithEPeq
TED
lentMANUSCRIPT
ui
va
amounts of the metal salts. Signals for the triazole, the -OH and
other phenolic protons were monitored for changes. The -OH signal
which appears at 10.53 ppm sharpens immediately upon addition of
each cation suggesting that the hydroxyl group is significantly
2+
affected.(49, 50) With the exception of Cu , inappreciable changes
2
2
were observed for the triazole Csp –H and phenolic Csp -H’s.
Copper(II) showed a significant downfield shift for the triazole
2
Csp –H and O-H, 8.15 to 8.63 ppm (∆δ = 0.48 ppm) and 10.53 ppm
to 10.78 ppm (∆δ = 0.22 ppm), respectively (Fig. 5). In addition,
2
+
Cu was the only cation with which observable changes were noted
H10 H12H13
H11
H8
O-H
2
for the phenolic Csp -H’s signals which were shifted downfield as
well. Overall, results from this experiment demonstrated that the
2+
probe selectively binds to Cu and that the triazole and phenolic
groups participate in that binding.
1
Figure 6. Changes in partial HNMR (400 MHz) spectra of BPT
-
2
-3
(
~7.8 × 10 mol dm ) upon increasing equivalents of Cu(II)
perchlorate salt in DMSO-D6. Image for colorimetric detection of
-
2
-3
(
a) BPT sensor (~1 × 10 mol dm ) and (b) BPT sensor and Cu(II)
-
2
-3
ion (2 × 10 mol dm ) in MeOH (inset).
3
.3 Steady state studies
BPT showed a colorimetric response with Cu(II) (Fig. 6
inset & see ESI,† Fig. S10). The faint yellow tinge of the probe in
methanol solution deepens in intensity (bright yellow) after addition
3
+
2+
of copper salt to the sensor. Color was also observed with Fe , Fe ,
H8
H10 H12 H13 H11
O-H
3+
and Cr ions (see ESI,† Fig. S10). However, this was a result of the
original perchlorate salt solutions and not because of binding
interaction of the metals with the probe. To quantify this sensing
1
Figure 5. Changes in partial H NMR (400 MHz) spectra of BPT performance, the steady state photophysical properties of the BPT
-
2
-3
(
~1.0 × 10 mol dm ) and of BPT upon addition of equivalent by itself and in the presence of various cations were first investigated
2+
2+
2+
+
3+
2+
2+
amount of selected cations (Zn , Cu , Fe , Ag , Al , Co , Ni ) using absorption and fluorescence spectroscopy in methanol owing
in DMSO-D6.
to higher solubility of BPT in this solvent (Fig. 7).
2+
1
Titration experiments with BPT and Cu using H NMR
spectroscopy further supported the importance of the triazole and the
phenolic groups in binding (Fig. 6). Importantly, the downfield shift
2
of the triazole Csp –H signal was proportional to the equivalents of
2+
Cu . This trend indicated that the triazole group is a N-donor during
2
chelation.(51) The ∆δ-triazole Csp –H was applied in a Job’s plot. A
curve maximum at ~0.66 revealed a 2:1 binding interaction, BPT :
2+
Cu (see ESI,† Fig. S6). Beyond a certain point, signal broadening
due to a paramagnetic effect overwhelmed the spectrum with
increasing equivalents of copper(II).(52)
Figur
e
7.
-
5
-3
Absorption spectral variation of BPT (~2 × 10 mol dm ) with the
addition of 4.0 × 10 mol dm of metal perchlorate salts in
methanol.
-
4
-3
4

ACCEPTED MAFur
N
th
sensitivity to copper(II) over other cations in aqueous medium (Fig.
b).
U
erm
S
o
C
re,
R
co
I
m
P
p
T
ared to methanol, the molecule showed enhanced
9
Compared to all other metal ions, the characteristic
absorption spectrum of BPT displayed a far greater response to
copper (Fig. 7, see ESI,† Fig. S7). Baseline correction with each
metal salt was performed to negate the absorption due to molecular
+
relaxation (e.g. Li ) or d-d splitting of the transition metal ions, if
any.(53, 54) The absorption spectrum of BPT showed the lowest
energy absorption maximum at 285 nm in methanol, the π- π *
transition of the triazole substituted phenol rings (Fig. 7).(28, 55-57)
Appearance of a new band at 330 nm was prominent upon addition
of the copper(II) salt. Enhanced absorbance was also observed with
2+
2+
the addition of Ni and Co . However, competition experiments
2+
clearly demonstrated a selectivity for Cu over all other ions and
NMR studies showed no change in the BPT chemical shifts when
2+
2+
Ni and Co were added (Figs. 5 & 9). This confirmed that the
2+
2+
enhanced absorbance with Ni
and Co
resulted from a
contribution from the absorption of the perchlorate salts and not
binding.
Screening experiments were also performed in aqueous
2+
medium (Fig. 8). As in methanol, BPT showed selectivity for Cu .
2+
However, notably, the distinctive response to Cu was more
prominent in water. Upon addition of copper perchlorate a new
charge transfer band developed around 340 nm. This band was ~10
nm red-shifted from that in methanol (~330 nm) due to the enhanced
solvent polarity in water. Overall, results from both the aqueous and
methanol media studies point to the same binding mechanism for the
probe with copper ions.
-
5
-3
Figure 9. Metal ion selectivity towards BPT (~2 × 10 mol dm )
through absorption study in (a) methanol and (b) water. The black
bars indicate the normalized absorption of BPT in presence of ~4 ×
-
4
-3
1
0 mol dm of various metal ions. The red bars represent the
-
5
normalized absorption of BPT with the addition of ~2 × 10 mol
dm copper(II) perchlorate in presence of other metal ions.
-
3
2
+
To further investigate the sensitivity of BPT towards Cu ,
titration with various concentrations of copper ions was performed in
methanol because of the molecule’s higher solubility in this solvent.
Subsequent addition of copper(II) perchlorate to BPT induced a
gradual lowering of the lowest energy absorption band at 285 nm
with a concomitant development of a new band around 330 nm (Fig.
-
5
-3
Figure 8. Absorption spectral variation of BPT (~2 × 10 mol dm )
-
4
-3
with the addition of 4.0 × 10 mol dm of metal perchlorate salts in
water.
1
0). Emergence of a new lower energy absorption band indicated
relaxation of the conjugated electron network. This increases the
Competition experiments were performed to evaluate the
practical use of the sensor. These experiments were carried out in
both methanol and water (Fig. 9). Treated separately with 1
2
+
possibility for charge transfer between BPT and the Cu ions.
Importantly, the presence of two well-defined isosbestic points at
272 nm and 298 nm indicated the formation of a unique complex
2+
equivalent of Cu ions in presence of 20 equivalents of other
2+
3
+
2+
+
3+
3+
2+
2+
2+
between the probe and Cu .(58-60) This experiment showed the low
interfering metal ions (Fe , Fe , Ag , Cr , Al , Co , Ni , Cd ,
2+
2+
2+
+
detectable limit of Cu with BPT in the submicromolar range of ~2
Zn , Mg and Li ), BPT demonstrated remarkable selectivity for
Cu . Other cations did not interfere with BPT’s detection of Cu .
-
6
-3
2+
2+
× 10 mol dm . This is much lower than its toxic level, 20µg/g, or
5

the recommended concentration of copper(II) io
2
A
n i
C
n d
C
ri
E
nk
P
in
TED
g
wa
ter,MANUSCRIPT
1
1


1

.

1
mg/L.(61)
=
+

(1)
∆A
∆A
K[L] ∆A
max

max
2
+
-6
-3
[
Cu ] x 10 mol dm
0
∆A = A
– A and ∆Amax = A – A ;
x 0 ∞ 0
0
.20
0
.4
.8
.2
where, A , A and A are the absorbances of the probe (BPT) in the
0
0
x
∞
1
2
3
4
8
absence, at an intermediate concentration and at a concentration of
complete interaction with copper ions at 330 nm, respectively. K is
the binding constant and [L] is the concentration of Cu .
0.15
2
+
1
6
2
4
2+
0.10
The binding plot of 1/∆A against 1/[Cu ] depicted
40
8
0
deviation from linearity at the higher concentrations of copper salt
1
18
56
30
00
70
2
+
1
2
3
3
indicating the formation of 2 : 1 binding complex of BPT with Cu
Fig. 12).(65) This substantiated the result obtained from Job’s plot
from both spectroscopic techniques.
0.05
(
438
0.00
300
350
400
450
120
Wavelength (nm)
Figure 10. Absorption spectral variation of BPT (~2 × 10 mol dm
with the addition of Copper perchlorate hexahydrate in methanol.
Copper salt concentrations are provided in the legends.
-
5
-
100
3
)
8
0
0
6
2+
The stoichiometry of BPT with Cu was determined with
Job’s plot using the absorption band at 330 nm (Fig. 11). The graph
was plotted between the difference in the absorbance, ∆A = A –A ,
40
20
x
0
2+
and the mole fraction, [BPT]/[BPT+Cu ]. The curve, fitted with the
non-linear fit parameter of ORIGIN 8.0 software, had a maximum at
5
6
6
6
6
0.0
5
.0x10 1.0x10 1.5x10 2.0x10 2.5x10
2+
0
.65. This indicated a 2:1 stoichiometric complex, BPT : Cu ,
2
+
-1
3
1
1/ [Cu ] (mol dm )
consistent with results of the H-NMR Job’s plot (see ESI,† Fig.
S6).(58)
Figure 12. Benesi-Hildebrand plot of BPT with addition of Copper
perchlorate hexahydrate showed deviation from linearity.
0
0
0
0
0
.016
.012
.008
.004
.000
After studying the binding characteristics of copper(II)
ions with BPT through steady state absorption, we shifted our
interest to investigate the fluorescence of the probe with the metal
ions. Photoexcitation of BPT at 290 nm yielded a broad emission
band, λmax = 370 nm, in methanol (Fig. 13). Successive addition of
copper salt revealed gradual quenching of the probe’s fluorescence.
Different levels of fluorescence quenching were also observed with
other metal ions (see ESI,† Fig. S8). The fluorescence quenching
2
+
X = [BPT]/
0.2 0.4
[
BPT+ Cu
]
2+
governed by Stern-Volmer equation F /F = 1+ K [Cu ] revealed a
0
SV
0
.0
0.6
0.8
1.0
linearity of the corresponding plot (see ESI,† Fig. S9). F and F are
2+
0
[
BPT]/ [BPT+ Cu ]
the fluorescence intensities in the absence and presence of the
2+
quencher, Cu , respectively. K is the Stern-Volmer quenching
SV
Figure 11. Job’s plot of BPT with Copper(II) perchlorate
hexahydrate in methanol. The absorbance was monitored at 330 nm.
constant. The fluorescence was monitored at the emission maximum
of BPT fluorescence. Slope of the plot yielded the K value as 6.96
SV
4
-1
3
×
10 mol dm implying that the fluorescence quenching occurred
because of binding of Cu(II) ion with BPT and not through
diffusional collision between the two interacting species.
Further insight into the stoichiometry of the complex
formed and binding of the probe with copper ions was gained from
the Benesi-Hildebrand method following the modified equation
(Eq.1) from the absorption data:(28, 62-64)
6

ACCEPTED MAN
T
U
he
empirical potential PM6 for
. This study used the Spartan 2010 equilibrium conformer
S
co
C
n
R
for
I
m
P
a
T
tional analyses were performed with the semi-
A
,
B
and . MMFF was used for
C
D
search algorithm, which examined 10000 conformers of each
system.(66) The lowest energy conformation for each system
was minimized in Gaussian 09W(67) using DFT-UB3LYP
level of theory and the 6-31G* basis set. Water was chosen as
the solvent using the default implicit solvent model. The lowest
energy conformation of each system is shown in Figure 14.
The lowest energy BPT conformation has the two triazole
groups nearly planar with each other. Within each arm, the phenyl
ring is planar with the triazole, and both arms have oxygen atoms
pointing in the same direction, a position that would allow for
intramolecular hydrogen bonding. In the actual X-ray structure, the
triazole rings of each molecule are rotated 81° with respect to each
other and the phenyl ring is rotated 60° with respect to the triazoles.
In this case, each molecule interacts with four neighbouring
-
5
-3
Figure 13. Fluorescence quenching of BPT (~2 × 10 mol dm )
with the addition of Copper perchlorate hexahydrate in methanol. molecules through intermolecular hydrogen bonding. This
Copper salt concentrations are provided in the legends.
intermolecular interaction greatly affects the geometry in the solid
state, thus the difference from the computationally-predicted
conformer (Figs. 1-3).
3
.4 Computational Studies
Based on the literature-precedent for the interaction of
For a 1:1 binding ratio with BPT and copper ion, structure
B, predicts binding with the triazole nitrogens (Scheme 2). For the 1
2+
Cu(II) with triazole systems(27) and the current experimental results,
plausible binding modes of BPT with Cu(II) were explored. For a
thorough analysis, the conformation of BPT and various
:
2 BPT : Cu complex, the predicted lowest energy binding mode
has both copper ions chelating with the triazole nitrogen atoms and
the oxygen atoms of the phenols.
2+
stoichiometric ratios of BPT : Cu were investigated: sensor only
2+
2+
2+
In the prediction for the 2 : 1, BPT : Cu , binding
interaction, the coordination of BPT to the metal at higher
concentrations of copper occurs through interaction with the triazole
nitrogens and carbonyl groups.
(
A), 1 : 1 (B, sensor : Cu ), 1 : 2 (C, sensor : Cu ) and 2 : 1 (D,
2+
sensor : Cu ) (Scheme 2).
O
H
O
H
OH
HO
N
N N N
N
N
Cu2+
Cu2+
BPT- Cu2+ (B)
1
eq.
O
O
OH
HO
O
N
O
N
Cu2+
OH
Cu2+
N
N N N
N
N
N
N
Cu2+
HO
N
N
BPT
A
H
2
eq.
H
BPT- Cu2+ (2 eq.) (C)
(
A)
BPT
O
O
OH
HO
N N
N
N N
(2 eq.)
N
O
O
N
N
N
N Cu2+
N
N
HO
OH
BPT (2 eq.) - Cu2+ (D)
2
+
2+
Scheme 2. The proposed binding mode of BPT and Cu metal
cation showing sensor : Cu at 1 : 1 (
binding mode.
Cu
2
+
B); 1 : 2 (C) and 2 : 1 (D)
(
B)
7

2
+
ACCEPTED MAbin
N
din
U
g
S
C
C
u
RI
over other cations. Notably, this selectivity and
P
T
sensitivity is especially prominent in aqueous medium.
Two isosbestic points in absorption experiments proved
2+
the formation a new BPT-Cu species. The triazole group is an N-
donor during binding as revealed by NMR and computational
studies. Overall, Job’s plots based on two different experiments,
NMR and UV-vis spectroscopy, indicate a 2 : 1, sensor : cation,
stoichiometry. Computational studies suggest structure D as the most
2
+
2
+
Cu
Cu
2
+
probable binding motif (Fig. 13). Thus, it is likely that the Cu
selectivity is achieved by the N-donating ability of the triazole
groups in conjunction with the binding cavity formed between these
triazole-phenol moeities.
(
C)
Currently, our work focuses on synthesizing novel
molecular sensors that can be applied to dual sensing (pH, cation,
anion), molecular switches, and logic gate applications. Studies on
2+
BPT’s selective detection of Cu has influenced the direction of this
new work. Results reported here indicate that modifications can be
made to the backbone of the molecule to enhance the signalling
response, for example adding functional groups or aromatic moieties
2
+
Cu
that provide
a
higher degree of conjugation in the
molecule. However, the triazole-phenol unit, as is present in the
structure of BPT, must be preserved to maintain selectivity and
2+
sensitivity for Cu .
(
D)
Figure 14. Lowest energy conformation for BPT
(
A
), BPT
), two BPT
D) from the conformational analysis.
Supporting Information:
2+
2+
with one Cu2 ion (
B), BPT with two Cu ion (C
CCDC
crystallographic data for this paper. These data can be obtained
free of charge via
1449447
contains
the
supplementary
+
with one Cu ion (
Based on complex formation energies, calculations suggest
2+
http://www.ccdc.cam.ac.uk/conts/retrieving.html (or from the
Cambridge Crystallographic Data Centre, 12, Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033).
Supporting information for this work has been provided
with the current manuscript.
that 1 : 2 (
C) and 2 : 1 (D), BPT : Cu , are possible (Table 2).
Of the two, the values indicate that a binding mode of 2 : 1 (
D
)
2
+
is most likely. Moreover,
D predicts that Cu resides in a
cavity created between the triazole-phenol units, and that
binding is via triazole N-donation without the participation of
the phenolic oxygen groups. This predicted probe-to-metal
interaction is most consistent with results of the NMR titration
studies and Job’s plots (Figs. 3 & 6, see ESI,† Fig. S6).
Acknowledgements
The authors acknowledge the Department of Chemistry, Georgia
Southern University (GSU), Honors Research Fund and the College
Office of Undergraduate Research (COUR) for the financial
assistance. DG and WM gratefully acknowledge the financial
support from Office of Naval Research (Award number:
N000141210589). JG, SL and KA greatly acknowledge the support
of the National Science Foundation (Award Number: NSF-CHE
Table 2. Calculated Enthalpies of Formation
2+
Structure BPT : Cu
complex E in kJ/mol
-623.9
B
C
D
1 : 1
1 : 2
2 : 1
-777.2
-839.2
(REU) 1359229). We thank Dr. Jeffrey Orvis for helpful discussions.
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Corresponding Author: Email: kaiken@georgiasouthern.edu and
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ACCEPTED MANUSCRIPT
TITLE: Spectroscopic Investigation of Bis-Appended 1,2,3-Triazole Probe for the Detection of
Cu(II) Ion
HIGHLIGHTS:
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bis-triazole chemosensor is selective for Cu(II) detection
selectivity and sensitivity for Cu(II) is probed in both aqueous and methanol media
the chemosensor has a more prominent response to Cu(II) in water
triazole units are N-donors during binding
binding occurs in a 2 : 1 stoichiometry, probe : Cu(II)