Self-assembly of pyrene boronic acid-based chemodosimeters for highly efficient mercury(II) ion detection

Article abstract of DOI:10.1016/j.tetlet.2019.151048

A new chemodosimeter consisting of pyrene and boronic acid (1) for the detection of Hg²⁺ ions is described. The amphiphilic nature of 1 leads to self-assembly in aqueous solution and the high electron density throughout the aggregated pyrene units provides an outstanding platform for energy and electron transport. Self-assembled 1 exhibits a selective and sensitive fluorescence response to Hg²⁺ ions, where the Hg²⁺ ion allows a fast transmetallation of 1, which drastically reduces its fluorescence. The Stern-Volmer (SV) quenching constant for the fluorescence quenching of self-assembled 1 by Hg²⁺ ions is approximately 1.8 × 10⁶ M^?1, and Hg²⁺ ions can be sensed with a detection limit of 6.6 × 10^?9 M. In addition, self-assembled 1 exhibits excellent sensing performance at nano-molar concentration levels for Hg²⁺ ion contamination of tap water, fresh water, and seawater.

Full text of DOI:10.1016/j.tetlet.2019.151048

Tetrahedron Letters xxx (xxxx) xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Self-assembly of pyrene boronic acid-based chemodosimeters for highly
efficient mercury(II) ion detection
1
1
⇑
Sun Woo Lee , Seung Yeob Lee , Seoung Ho Lee
Department of Chemistry, Institute of Basic Sciences, Daegu University, Gyeongsan 38453, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
A new chemodosimeter consisting of pyrene and boronic acid (1) for the detection of Hg2+ ions is
described. The amphiphilic nature of 1 leads to self-assembly in aqueous solution and the high electron
density throughout the aggregated pyrene units provides an outstanding platform for energy and elec-
tron transport. Self-assembled 1 exhibits a selective and sensitive fluorescence response to Hg2+ ions,
where the Hg2+ ion allows a fast transmetallation of 1, which drastically reduces its fluorescence. The
Stern-Volmer (SV) quenching constant for the fluorescence quenching of self-assembled 1 by Hg2+ ions
is approximately 1.8 Â 106 MÀ1, and Hg2+ ions can be sensed with a detection limit of 6.6 Â 10À9 M. In
addition, self-assembled 1 exhibits excellent sensing performance at nano-molar concentration levels
for Hg2+ ion contamination of tap water, fresh water, and seawater.
Article history:
Received 10 June 2019
Revised 9 August 2019
Accepted 14 August 2019
Available online xxxx
Keywords:
Chemodosimeters
Self-assembly
Amplified quenching
Mercury ion sensors
Ó 2019 Elsevier Ltd. All rights reserved.
Mercury has been widely utilized in various fields, such as
chemistry, medicine, and biology. The resulting wide environmen-
tal availability has led to an increased incidence of diseases related
to mercury poisoning [1]. In particular, because Hg2+ ions act on
the human nervous system and causes various diseases such as
acrodynia, Hunter-Russell syndrome, and Minamata disease, mer-
cury has been considered one of the most dangerous pollutants in
the environment [2–4]. Among many chemical sensors, chemosen-
sors based on fluorescence changes are used to detect a variety of
ions or biomaterials due to their high selectivity and sensitivity [5–
7]. Nevertheless, the Hg2+ ion fluorescence sensors developed to
date have shown low selectivity for Hg2+ ions in complex condi-
tions including various competing metal ions, such as tap water,
fresh water, and seawater. They also have limitations in detection
at the level of 10 nM Hg2+ ion, which is the reference value for con-
taminated water as suggested by the World Health Organization
(WHO) [8].
In the past decades, various sensors/probes have been devel-
oped to overcome low selectivity and sensitivity. Among them,
chemodosimeters, which are based on chemical reactions, have
attracted considerable attention due to their high selectivity, and
significant effort has been devoted to the development of sensors
based on simple and straightforward reactions. Recently, chemod-
osimeters based on the transmetallation of aromatic derivatives
with boronic acid have been reported, in which the probe showed
high selectivity for the Hg2+ ion over other competitive metal ions
[9]. While the chemodosimeter provides a useful platform for
selectivity, the specific reaction for the conversion of one group
to another can sometimes be limited, which leads to a relatively
low sensitivity.
Conjugated polymer (CP)-based sensors have also been exten-
sively investigated because the molecular wire effect in the conju-
gated backbone of CPs gives rise to amplified fluorescence
quenching that enhances the sensory response to the analytes
[10–13]. In a molecular wire system, amplified quenching is
induced via both intrapolymer and interpolymer exciton migra-
tion, even though the polymer backbones are partially affected
by the analytes [14,15]. However, despite such potential advan-
tages of CPs as a highly sensitive sensor, their practical application
is often limited by the low solubility and complex sensing behav-
iors induced by a variety of chain lengths in aqueous solution [16].
In this work, taking advantage of the sensing response of both
chemodosimeters and CPs, a self-assembled chemodosimeter has
been designed. The amphiphilic chemodosimeter 1, consisting of
pyrene and boronic acid, exhibits self-assembly in aqueous solu-
tion, where the pyrene units aggregate against the hydrophilic nat-
ure of water (Fig. 1). This new probe exhibits high selectivity and
sensitivity for Hg2+ ions via both chemical reaction and amplified
fluorescence quenching, respectively. Moreover, this new probe
represents an efficient receptor for Hg2+ ions even in a contami-
nated environment containing various competitive metal ions.
Fig. 1 shows the structure of amphiphilic chemodosimeter 1
with pyrene and boronic acid. Compound 1 was synthesized from
⇑
Corresponding author.
1
The authors equally contributed to this work.
https://doi.org/10.1016/j.tetlet.2019.151048
0040-4039/Ó 2019 Elsevier Ltd. All rights reserved.
Please cite this article as: S. W. Lee, S. Y. Lee and S. H. Lee, Self-assembly of pyrene boronic acid-based chemodosimeters for highly efficient mercury(II) ion
detection, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.151048

2
S.W. Lee et al. / Tetrahedron Letters xxx (xxxx) xxx
Fig. 1. Structure of chemodosimeter 1 and schematic illustration of its self-assembly and plausible sensing process.
commercially available pyrene by an ester-protected precursor
route via an Ir-catalyzed reaction (Scheme S1 and Fig. S5) [17].
Compound 1 features hydrophobic pyrene and water-solubilizing
boronic acid, generating a self-assembled form in aqueous media,
in which the boronic acid was selected to cause transmetallation
by Hg2+ ions [18,19].
The self-assembly of 1 was elucidated by scanning electron
microscopy (SEM) and dynamic light scattering (DLS) studies.
Fig. 2a shows the Field Emission Scanning Electron Microscopy
(FE-SEM) image of 1 that was deposited on a carbon grid from
5.0 Â 10À6 M in H2O solvent. Compound 1 exhibits a granular
structure with an average grain size of approximately 234 nm.
Fig. 2c shows the distribution profiles for the scattering popula-
tions with the hydrodynamic radii obtained from DLS for 1 in
H2O. As expected, the DLS result of 1 in H2O is very similar to that
of SEM, where a solution state of 1 represents a relatively large par-
ticle (396 nm) with a maximum size of approximately 459 nm. On
the other hand, DLS results were not obtained in methanol, which
suggests that although 1 undergoes intermolecular aggregation in
water, its accumulation is restricted to narrow limits.
The self-assembled
1 was further investigated by UV/Vis
absorption and fluorescence spectroscopy in H2O and MeOH. As
shown in Figs. 3 and S1, 1 in H2O (red solid line) exhibits a broad
shoulder band at 375 nm with the molar extinction coefficient
(e = 20038 MÀ1 cmÀ1) in the UV/Vis absorption spectra whereas
its fluorescence emission displays similar features to that of MeOH
(blue dashed line). The excimer emission of 1 was not observed
within the range of low (1 lM) to high (50 lM) concentrations of
1 (Fig. S2). It is evident that the pyrene moieties of 1 are stacked
in the ground state and may not be in a favorable configuration
for excimer formation [20]. The aggregation of 1 in water is attrib-
uted to the intermolecular hydrophobic interaction between the
centered pyrene moieties against the hydrophilic nature of water.
Fig. 4 shows the fluorescence intensity changes of 1 upon the
addition of Hg2+ ions in water. This addition induces highly effi-
cient fluorescence quenching; maximum quenching of approxi-
mately 99.4% is observed upon the addition of 3.0 Â 10À6 M of
Hg2+ ions. In contrast, the addition of a variety of other metal ions
Fig. 2. SEM images of (a) 1 and (b) 1-Hg2+; (c) hydrodynamic radii obtained from
DLS for 1 (5.0 Â 10À6 M) upon the addition of Hg2+ (5.0 Â 10À6 M) in H2O.
conducted in the presence of both Hg2+ ions and excess amounts
of other metal ions in a mixture (Fig. S4). As expected, the fluores-
cence changes of 1 induced by the Hg2+ ions were independent of
the presence or absence of other metal ions. Thus, these results
demonstrate the very good selectivity of 1 toward Hg2+ ions rela-
tive to other metal ions in aqueous solution.
(Li+, Na+, K+, Cs+, Ag+, Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Fe2+, Co2+, Ni2+
,
Cu2+, Zn2+, Cd2+, Hg2+, Sn2+, Pb2+, and Fe3+) to 1 only negligibly
affects the fluorescence intensity (Fig. 4a and S3). Fluorescence
quenching of 1 by Hg2+ ions likely occurs via a chemical reaction
due to the transmetallation of aryl boronic acid by Hg2+ ions
(Fig. 1), where the fluorescence quenching most likely occurs
through electron transfer from the excited pyrene to the com-
plexed mercury atom [9,18,19]. Competition experiments were
1H NMR studies provided information on the transmetallation
of 1 with Hg2+ ions in DMSO d6. A large up-field shift (0.09 ppm)
was observed for the protons at the 4,10-positions of 1 upon the
addition of Hg2+ ions (Fig. S5). Considering that the protons at
the 4,10-position of the precursor (boronic ester form) showed a
Please cite this article as: S. W. Lee, S. Y. Lee and S. H. Lee, Self-assembly of pyrene boronic acid-based chemodosimeters for highly efficient mercury(II) ion
detection, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.151048

S.W. Lee et al. / Tetrahedron Letters xxx (xxxx) xxx
3
studied by SEM and DLS analysis as shown in Fig. 2. The main fea-
ture is that 1-Hg2+ exhibits an increased size of approximately 1.6-
fold in both results, where its size increased approximately from
234 nm to 364 nm in SEM and from 396 nm to 619 nm of average
sizes in DLS, respectively. Interestingly, the inter-agglomerate
aggregation between self-assembled 1 was not observed in the
SEM image upon the addition of Hg2+ ions. Therefore, it is likely
that the addition of Hg2+ ions reorganizes 1 in the direction of
increasing interaction of additional pyrenes inside the aggregate
with its size expansion.
In order to quantify the sensory response of self-assembled 1 to
Hg2+ ions, a Stern-Volmer (SV) quenching study was carried out in
both methanol and aqueous solution. Figs. 4b and 5 show the
changes in fluorescence intensity and the corresponding SV plot
(monitored at k = 387 nm) upon the addition of various amounts
of Hg2+ ions. In aqueous solution, the SV plot exhibits a linear pro-
file at very low Hg2+ ion concentration, where an SV quenching
constant KSV = 1.8 Â 106 MÀ1 was recorded, and the quenching pro-
file becomes nonlinear with further increase in Hg2+ ion concentra-
tion. This high KSV value corresponds to the result of amplified
fluorescence quenching in the conjugated polymers.[14,21–23]
The analytical detection limit (ADL) for Hg2+ ions is 6.6 Â 10-9 M,
which is one of the lowest value reported to date (Table S1)
[9,24–28]. The fact that the fluorescence of self-assembled 1 is effi-
Fig. 3. UV/Vis absorption and fluorescence emission spectra of 1 (5.0 Â 10À6 M) in
H2O and MeOH. Excitation at 337 nm.
Fig. 4. Fluorescence intensity changes of 1 (5.0 Â 10À6 M) in H2O upon the addition
of (a) various metal ions (10 Â 10À6 M) and (b) various amounts of Hg2+ ions. The
chloride salts of metal ions: 1: blank, 2: Li+, 3: Na+, 4: K+, 5: Cs+, 6: Mg2+, 7: Ca2+, 8:
Sr2+, 9: Ba2+, 10: Mn2+, 11: Fe2+, 12: Fe3+, 13: Co2+, 14: Ni2+, 15: Cu2+, 16: Ag+, 17:
Zn2+, 18: Cd2+, 19: Hg2+, 20: Sn2+, 21: Pb2+. Excitation at 337 nm; fluorescence
intensity was monitored at 387 nm.
significant chemical shift (0.36 ppm down-field) upon conversion
to the acid form, such a remarkable chemical shift after the addi-
tion of Hg2+ ions to 1 is the result of transmetallation of the aryl
boronic acid. The transmetallation of 1 with Hg2+ ions was further
Fig. 5. (a) Stern-Volmer (SV) plot of 1 (5.0 Â 10À6 M) titrated with Hg2+ ions in H2O
and MeOH; (b) Time-course analysis of transmetallation upon the addition of
various concentrations of Hg2+ ions. Excitation at 337 nm; fluorescence intensity
was monitored at 387 nm.
Please cite this article as: S. W. Lee, S. Y. Lee and S. H. Lee, Self-assembly of pyrene boronic acid-based chemodosimeters for highly efficient mercury(II) ion
detection, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.151048

4
S.W. Lee et al. / Tetrahedron Letters xxx (xxxx) xxx
ciently quenched in water is believed to be due to the efficient
exciton migration throughout the aggregated pyrenes [29,30]. In
methanol, however, where 1 does not aggregate, the fluorescence
is not effectively quenched by Hg2+ ions (Fig. S6), and the SV plot
in methanol has a much lower gradient (KSV = 5.5 Â 105 MÀ1) than
in aqueous solution. The behavioral difference of 1 in methanol and
in aqueous solution indicates that its assembly formation plays an
important role in increasing the sensitivity to Hg2+ ion detection,
possibly owing to efficient exciton migration in the agglomerated
state. In addition, the time-course transmetallation of 1 upon the
addition of various concentrations of Hg2+ ions was analyzed in
aqueous solution. As shown in Fig. 5b, the fluorescence intensity
gradually decreased as a function of time in the presence of Hg2+
ions. Its quenching effect was accelerated as the concentration of
Hg2+ ions increased, and the fluorescence quenching was com-
pleted within 20 min even at very low (1 lM) concentration. This
analysis clearly provides the kinetic information for applying
Fig. 7. Fluorescence of self-assembled 1 test strips exposed to various Hg2+ ion
concentrations in water, then dried in air.
self-assembled 1 as a practical sensor.
An efficient sensing probe is expected to be capable of detecting
trace amounts of Hg2+ ions in complex conditions that include var-
ious competing substances, such as metal ions, hydrogen ions, and
biogenous substances. Finally, we explicitly tested the perfor-
mance of 1 as a practical sensor. Fig. 6a compares the fluorescence
response of 1 in DI water and a variety of Hg2+ ion-contaminated
conditions such as tap water, fresh water, and seawater. Self-
assembled 1 exhibited reduced fluorescence compared to DI water
in mercury-contaminated conditions, and these changes were con-
sistent regardless of probe concentration. Furthermore, as shown
in Fig. 6b, even very small changes in Hg2+ ion concentration could
be measured in tap water and fresh water, with SV quenching con-
stants of KSV = 5.6 Â 106 MÀ1 and 2.5 Â 106 MÀ1
, respectively,
which are as high as in pure water. This high selectivity and sensi-
tivity of self-assembled 1 under practical conditions demonstrates
its superior performance as a fluorescence sensor that can be easily
applied to biological or environmental applications that have a
wide variety of interferences.
The applicability of self-assembled 1 as a commercial Hg2+ ion
sensor was evaluated visually under illumination with near-UV
light. Fig. 7 illustrates the fluorescence response to various Hg2+
ion concentrations in a test strip that was easily fabricated by
immersing filter paper into the solution of 1 (5.0 Â 10À6 M) and
drying in air. The prepared test strips were immersed into aqueous
solutions of Hg2+ ions with different concentrations for 20 min and
then the test strips were excited under a UV lamp (Fig. S7). The
images clearly show that the fluorescence intensity of 1 can range
the hundred nanomolar (1.0 Â 10À7 M) to hundred-micromolar
(1.0 Â 10À4 M) levels of Hg2+ ion concentration. This value is
among the highest sensitivity reported to date for Hg2+ ion detec-
tion [31]. The resulting fluorescence intensities in the test strips
allowed us to roughly measure the Hg2+ ion contamination in
aqueous media and demonstrate promising potential application
in the development of commercial sensors.
In conclusion, we have devised a novel, self-assembled system
for a chemodosimeter capable of detecting Hg2+ ions. The fluores-
cence intensity of self-assembled 1 was selectively and sensitively
quenched with nano-molar Hg2+ ion concentrations in practical
conditions that include a wide variety of interferences. We have
demonstrated that the self-assembly of a chemodosimeter pro-
vides both high selectivity and sensitivity because it is based on
both chemical reactions and amplified fluorescence quenching in
Hg2+ ion detection. As most chemical sensors developed to date
are based on a single molecular system, our findings are likely to
enhance the sensitivity of the developed chemical sensors.
Acknowledgments
This work was supported by the National Research Foundation
Fig. 6. (a) Fluorescence intensity changes with increasing concentration of
1
of
Korea
(NRF-2016R1D1A1B03931447
and
NRF-
(5.0 Â 10À6 M) in DI water, tap water, fresh water, and seawater, and (b) titration
profiles of 1 (5.0 Â 10À6 M) with Hg2+ ions in tap water and fresh water. Excitation
at 337 nm; fluorescence intensity was monitored at 387 nm.
2019R1I1A3A01058982) and Daegu University Research Scholar-
ship Grants.
Please cite this article as: S. W. Lee, S. Y. Lee and S. H. Lee, Self-assembly of pyrene boronic acid-based chemodosimeters for highly efficient mercury(II) ion
detection, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.151048

S.W. Lee et al. / Tetrahedron Letters xxx (xxxx) xxx
5
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Please cite this article as: S. W. Lee, S. Y. Lee and S. H. Lee, Self-assembly of pyrene boronic acid-based chemodosimeters for highly efficient mercury(II) ion
detection, Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2019.151048