A novel berberine-based colorimetric and fluorometric probe for Hg2+ detection and its applications in water samples

Article abstract of DOI:10.1016/j.inoche.2021.108847

The development of small molecule fluorescent probes for detection of heavy metal ions is highly desirable in fluorescent sensors area, and mercury (Hg²⁺) is a heavy metal pollutant in environment and food chain processes. Herein, we reported the design and synthesis of a novel berberine-based fluorescent probe P1, which can specifically recognize Hg²⁺ in CH₃OH/PBS (8:2, v/v, pH = 7.4, 10 mM) solution by the colorimetric and fluorometric changes. The probe P1 displayed high selectivity, superior sensitivity and fast response toward Hg²⁺ with a low detection limit and a wide range of pH values. This probe can provide a convenient and effective way for Hg²⁺ detection on test paper strips. Moreover, the probe P1 can be applied to quantitatively detect Hg²⁺ in real environmental water samples.

Full text of DOI:10.1016/j.inoche.2021.108847

Inorganic Chemistry Communications 132 (2021) 108847
Contents lists available at ScienceDirect
Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
A novel berberine-based colorimetric and fluorometric probe for Hg2+
detection and its applications in water samples
Shutang Ruana, Yan Zhanga, Suzhen Wub, Yu Gaoa, Lijuan Yanga, Mingxin Lia, Yiqin Yanga,
,
,*
Zhonglong Wanga *, Shifa Wanga
a Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, College of Light Industry and Food, Nanjing Forestry
University, Nanjing 210037, China
b School of Basic Medicine, Gannan Medical University, Ganzhou 341000, China
A R T I C L E I N F O
A B S T R A C T
Keywords:
The development of small molecule fluorescent probes for detection of heavy metal ions is highly desirable in
fluorescent sensors area, and mercury (Hg2+) is a heavy metal pollutant in environment and food chain pro-
cesses. Herein, we reported the design and synthesis of a novel berberine-based fluorescent probe P1, which can
specifically recognize Hg2+ in CH3OH/PBS (8:2, v/v, pH = 7.4, 10 mM) solution by the colorimetric and fluo-
rometric changes. The probe P1 displayed high selectivity, superior sensitivity and fast response toward Hg2+
with a low detection limit and a wide range of pH values. This probe can provide a convenient and effective way
for Hg2+ detection on test paper strips. Moreover, the probe P1 can be applied to quantitatively detect Hg2+ in
real environmental water samples.
Berberine
Fluorescent probe
Colorimetric probe
Hg2+ detection
1. Introduction
as anti-bacterial agent [24], antiviral agent [25–27], antioxidant and
anticancer [28,29]. In addition, it is a valuable researching direction of
Hg2+ is a high toxic heavy metal pollutant and widely distributes in
water and soil [1–3]. Excessive Hg2+ in the bodies easily causes some
serious diseases, such as kidney damage [4], minamata disease [5],
endocrinium and nervous system damage [6], cognitive and motor
disorders [7]. It is necessary to control the content of Hg2+ in environ-
mental and agricultural products within safe limits [8].
fluorescence-based theranostics based on berberine for effective diag-
nosis and therapy in cancer cells [30].
In our previous work [31], a dual-functional fluorescent probe for
the detection of both Hg2+ and ClO─ has been designed and synthesized
from berberine. In order to further expand the application of berberine
and detect Hg2+ by the naked eye and fluorescence conveniently.
Herein, based on the desulfurization reaction of the mercaptal group, a
dual-mode berberine-based colorimetric and fluorometric probe was
designed and synthesized for the recognization of Hg2+. Meanwhile, the
probe P1 showed “turn-on” fluorescent response toward Hg2+ recogni-
tion in real water samples. Moreover, from the fluorescence detection
experiments, the probe P1 exhibited fast response, wide pH range, lower
detection limit, high selectivity and sensitivity.
During the past two decades, many chemical analysis methods have
been used for detecting toxic heavy metal, such as atomic absorption
spectroscopy [9], high resolution ICP-MS [10], spectrophotometry [11]
and fluorescent probe technique [12–15]. Among these detection
methods, fluorescent probe technique has been widely accepted owing
to its on-site detection, real-time analysis, high sensitivity, low cost and
fast response. Recently, a number of fluorescent probes have been re-
ported for detecting Hg2+ in real samples and living cells. However,
some probes were based on “turn-off” mechanism through the spin–orbit
coupling effect which cause fluorescence quenching [16–18]. Therefore,
the fluorescent probes for detecting Hg2+ based on “turn-on” mechanism
have attracted more and more attentions [19–22].
2. Experimental
2.1. Instruments and materials
Berberine is a kind of typical isoquinoline alkaloids extracted from
huanglian (Rhizoma coptidis) [23], and its derivatives were widely used
All chemicals and solvents were purchased from commercial sources
and used without further purification. 1H NMR and 13C NMR spectra
* Corresponding authors.
E-mail addresses: wang_zhonglong@njfu.edu.cn (Z. Wang), wangshifa65@163.com (S. Wang).
https://doi.org/10.1016/j.inoche.2021.108847
Received 19 June 2021; Received in revised form 23 July 2021; Accepted 5 August 2021
Available online 8 August 2021
1387-7003/© 2021 Elsevier B.V. All rights reserved.

S. Ruan et al.
Inorganic Chemistry Communications 132 (2021) 108847
Scheme 1. Synthesis of probe P1.
were recorded on a Bruker AV 400 spectrometer in DMSO‑d6 and tet-
ramethylsilane (TMS) as internal standard. High-resolution mass spectra
(HRMS) were tested by an America Agilent 5975c mass spectrometer.
UV–vis absorption spectra were recorded by a Shimadzu UV-2450 at the
room temperature. Fluorescence spectra were carried out on fluores-
cence spectrophotometer (LS 55, Perkin Elmer).
1H) ;ESI-MS (m/z): [Mꢀ Cl]+ : calcd. for C20H16ClNO5-Cl-, 350.1023;
found, 350.1049.
2.2.3. Synthesis of compound 4
Compound 3 (50 mg, 0.14 mmol) and 1,3-propanedithiol (45.4 mg,
0.42 mmol) were dissolved in CH2Cl2 (20 mL), and a catalytic amount of
BF3⋅Et2O (0.04 mL, 0.30 mmol) was added, and the mixture was reacted
at room temperature for 15 h under N2 atmosphere. The reacted mixture
was evaporated to remove off solvent, and the residue was purified by
recrystallization with CH3OH/Et2O (v/v = 2:1) to obtain compound 4 as
a red solid, 37.5 mg, yield: 57.3%. 1H NMR (400 MHz, DMSO‑d6) δ: 9.31
(s, 1H), 8.37 (s, 1H), 7.89 (s, 1H), 7.51 (s, 1H), 7.03 (s, 1H), 6.30 (s, 1H),
6.15 (s, 2H), 4.60 (t, J = 6.2 Hz, 2H), 3.81 (s, 3H), 3.30 (s, 2H), 3.10 (t, J
= 6.2 Hz, 2H), 2.90 (dt, J = 14.1, 3.5 Hz, 2H), 1.24 (d, J = 3.3 Hz, 2H) ;
ESI-MS (m/z): [Mꢀ Cl]+ calcd. for C20H16ClNO5-Cl-, 440.0985; found,
440.1019.
2.2. Synthesis of probe P1
As shown in Scheme 1, berberine was selectively demethylated
under vacuum and heating conditions, and then acidized and formylated
to get compound 3. The probe P1 was obtained by condensation of
compound 3 with 1,3-propanedithiol. The chemical structure of the
above compounds and probe P1 was characterized by 1H NMR and HR-
MS (Fig. S1-S7).
2.2.1. Synthesis of compound 2
Berberine chloride (10.0 g, 26.9 mmol) was heated at 180–190 ◦C for
30–60 min under vacuum to afford dark wine solid, which was washed
with MeOH (80 mL) and filtered to afford the red compound. And this
crude product was added C2H5OH (100 mL) and HCl (3.0 M, 70 mL) to
stir for 6 h to obtain yellow material, which was washed with CH3OH/
Et2O (v/v = 3:1) 3 times (3 × 60 mL) to afford compound 2 as a yellow
solid, 8.87 g, yield: 92.4%. 1H NMR (400 MHz, DMSO‑d6) δ: 11.31 (s,
1H), 9.97 (s, 1H), 8.88 (s, 1H), 8.12 (d, J = 8.9 Hz, 1H), 7.82 (s, 1H),
7.75 (d, J = 8.9 Hz, 1H), 7.10 (s, 1H), 6.21 (s, 2H), 4.96 (t, J = 6.3 Hz,
2H), 4.09 (s, 3H), 3.25 (t, J = 6.3 Hz, 2H);13C NMR (100 MHz, DMSO‑d6)
δ: 149.58, 147.61, 145.70, 145.30, 143.75, 136.52, 132.39, 130.33,
125.43, 120.56, 119.80, 118.03, 117.58, 108.32, 105.29, 101.94, 56.99,
54.89, 26.48;ESI-MS (m/z): [Mꢀ Cl]+ : calcd. for C19H16ClNO4-Cl─,
322.1074; found, 322.1074.
2.3. Spectroscopic measurements of probe P1
The absorption and fluorescence detection experiments were done in
CH3OH/PBS (8:2, v/v, pH = 7.4, 10 mM) solution at the room temper-
ature, and the excitation wavelength is 365 nm. The probe P1 stock
solution (2.5 × 10-4 M) was prepared in CH3OH. The test solution was
prepared by adding 100 μL stock solution to 10 mL CH3OH/PBS buffer
(8:2, v/v, pH = 7.4, 10 mM). The solutions of various analytes (5.0 × 10-
4
M) (including Na+, K+, Ca2+, Mg2+, Co2+, Al3+, Ni2+, Sn2+, Ag2+
,
Zn2+, Cu2+, I─, NO3─, AcO─, H2PO42─, S2─) were prepared in deionized
water.
2.4. Visualization of Hg2+ in solution by test paper
The filter paper was immersed into the CH3OH solution of probe P1
(2.5 × 10-4 M) and dried in air for 30 min. The treated test papers were
2.2.2. Synthesis of compound 3
Compound 3 was obtained according to the reported procedures
[31]. Compound 2 (1.0 g, 3.1 mmol) and hexamine (1.26 g, 9.0 mmol)
were dissolved in trifluoroacetic acid (18 mL), and reacted for 8 h at
85 ◦C. The reaction system was cooled to room temperature, and 3.0 M
HCl (15 mL) was added to react at 85 ◦C for another 2 h. The reacted
mixture was immediately poured into ice water, and extracted with
ethyl acetate (3 × 30 mL). The combined organic phase was washed with
distilled water and brine until neutrality, and then evaporated to remove
off the solvent. The residue was purified by silica gel chromatography
(CH2Cl2/CH3OH, 10:1, v/v) to give compound 3 as a yellow solid, 0.38 g,
yield: 34.6%. 1H NMR (400 MHz, DMSO‑d6) δ: 10.19 (s, 1H), 9.28 (s,
1H), 9.08 (s, 1H), 7.72 (s, 1H), 7.56 (s, 1H), 7.02 (s, 1H), 6.15 (s, 2H),
4.60 (t, J = 6.3 Hz, 2H), 3.77 (s, 3H), 3.10 (t, J = 6.4 Hz, 2H), 1.24 (s,
immersed in the Hg2+ solution with different concentrations (0
μM-500
μ
M) for 30 min at the room temperature. The fluorescence color changes
of filter paper were observed under day light and 365 nm UV light.
2.5. Quantitation of Hg2+ contamination in real water samples
The real water samples were respectively taken from Zhangjiang
river and Poyang lake, and the real water samples were utilized to
prepare CH3OH solutions (80%, 10 mM). Hg2+ solutions with different
concentrations (0, 50, 100, 150, 200, 250
μM) were added to the
aforesaid two water samples, and the fluorescence intensity of the water
samples were measured using a fluorescence spectrophotometer.
2

S. Ruan et al.
Inorganic Chemistry Communications 132 (2021) 108847
(b)500
400
300
200
100
0
(a)
0.25
0.20
0.15
0.10
0.05
P1
P1
P1+Hg2+
P1 + Hg
2+
2+
2+
+ Hg
+ Hg
300 350 400 450 500 550 600
450
500
550
600
650
700
Wavelength (nm)
Wavelength (nm)
Fig. 1. Absorption (a) and fluorescence emission (b) spectra of probe P1 (2.5 × 10-4 M) in CH3OH/PBS (8:2, v/v, pH = 7.4, 10 mM) solution in the presence and
absence of Hg2+ (5.0 × 10-4 M). λex = 365 nm. Inset: color changes of probe P1 solution after the addition of Hg2+ under daylight and 365 nm UV-light.
(a)800
(b)
450
400
350
300
250
200
150
P1
2+
P1 + Hg
600
400
200
0
100
200
300
400
500
2
4
6
8
10
12
Time (s)
pH
Fig. 2. (a) Fluorescence intensity of P1 (2.5 × 10-4 M) added to Hg2+ (5.0 × 10-4 M) in CH3OH/PBS (8:2, v/v, pH = 7.4, 10 mM) solution from pH = 2.0 to pH = 12.0
at 550 nm. Inset: color changes of P1 after the addition of Hg2+ from pH = 2.0 to pH = 12.0 under 365 nm UV-light. (b) Time-dependent fluorescence spectra of P1
(2.5 × 10-4 M) presence and absence Hg2+ (5.0 × 10-4 M) in CH3OH/PBS (8:2, v/v, pH = 7.4, 10 mM) solution (λem = 550 nm).
3. Results and discuss
probe P1 in the presence and absence of Hg2+ at the room temperature
were examined. As shown in Fig. 1a, the free probe P1 showed two
absorption peaks at 400 nm and 520 nm. Upon addition of Hg2+, the
original maximum absorption peaks were significantly reduced and the
new peaks were appeared obviously at 350 nm and 450 nm, and the
3.1. Spectroscopic properties of probe P1 to Hg2+
The UV–vis absorbance and fluorescence spectroscopic properties of
(b)
500
(a)
400
300
200
y = 0.5335 x + 184.0493
2
400
2.0 eqv.
R
= 0.9950
Hg2+
0.0 eqv.
300
200
100
0
450
500
550
600
650
700
0
100
200
300
400
500
2+] ( -6
10 mol/L
[Hg
)
Wavelength (nm)
Fig. 3. (a) Fluorescence spectra of P1 (2.5 × 10-4 M) in the presence of Hg2+ (0–2.0 eqv.) in CH3OH/PBS (8:2, v/v, pH = 7.4, 10 mM) solution. (b) Linear calibration
curve between the fluorescence intensity of P1 and Hg2+ (0–2.0 eqv.) at 550 nm.
3

S. Ruan et al.
Inorganic Chemistry Communications 132 (2021) 108847
(b)
(a) 500
2+
competing specise + Hg
competing specise
500
2+
400
300
200
100
0
P1 + Hg
400
300
200
100
0
competing species
450
500
550
600
650
700
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Wavelength (nm)
Competitive ions
(c)
Fig. 4. (a) Fluorescent spectra of P1 (2.5 × 10-4 M) with different competing ions (5.0 × 10-4 M) (including Na+, K+, Ca2+, Mg2+, Co2+, Al3+, Ni2+, Sn2+, Ag2+, Zn2+
,
Cu2+, I─, NO3─, OAc─, H2PO42─, S2─, Hg2+) in CH3OH/PBS (8:2, v/v, pH = 7.4, 10 mM) solution (λex = 365 nm). (b) The fluorescence intensity of P1 (2.5 × 10-4 M)
with Hg2+ (5.0 × 10-4 M) in the presence of different competitive anions (5.0 × 10-4 M) in CH3OH/PBS (8:2, v/v, pH = 7.4, 10 mM) solution (λex = 365 nm). (c)
Photographs of P1 (2.5 × 10-4 M) with different competing ions (5.0 × 10-4 M) in CH3OH/PBS (8:2, v/v, pH = 7.4, 10 mM) solution under day-light and 365 nm
UV light.
colors of the solution changed from light red to pale yellow under
daylight.
Hg2+ concentration from 0 to 2.0 equiv., the emission intensities of
probe P1 solution enhanced at 550 nm and quenched at 450 nm, which
may be attributed to an ICT (intra-molecular charge transfer) process
[32]. Furthermore, the emission intensities at 550 nm showed a good
The fluorescence properties of probe P1 were investigated. As shown
in Fig. 1b, the free probe P1 displayed two weak fluorescence emissions
at 450 nm and 550 nm with excitation at 365 nm. However, upon
addition of Hg2+, the fluorescence intensity at around 550 nm was
significantly enhanced, and the color of the solution changed from pale
blue to yellow green. These results showed that the probe P1 can serve
as a colorimetric and fluorometric probe for Hg2+ detection.
linear relationship over the concentration range from 0 μM to 500 μM (y
= 0.5335x + 184.0493, R2 = 0.9950). The detection limit for Hg2+ was
calculated to be 5.4 μM based on 3σ/k method (Fig. 3b).
3.4. Selectivity and competivity of probe P1 to various analytes
3.2. Response time and effect of pH values of probe P1 to Hg2+
The selectivity experiments were carried out with the addition of
various analytes. As shown in Fig. 4a, the fluorescence spectral changes
of probe P1 (2.5 × 10-4 M) were examined in CH3OH/PBS (8:2, v/v, pH
= 7.4, 10 mM) solution upon addition of different various analytes (5.0
Influence of pH from 2.0 to 12.0 on the fluorescence responses of
probe P1 with and without Hg2+ were investigated as shown in Fig. 2a,
It was known from the results of fluorescent experiments that the fluo-
rescence emission intensities were stable in a wide pH range from 3.0 to
10.0, which indicated that the probe P1 was suitable for detecting Hg2+
under the real water samples in a wide pH range. In addition, the time-
dependent fluorescence results demonstrated that the probe P1 could
remain stable and recognize Hg2+ with a short response time (Fig. 2b).
× 10-4 M, including Na+, K+, Ca2+, Mg2+, Co2+, Al3+, Ni2+, Sn2+, Ag2+
,
Zn2+, Cu2+, I─, NO3─, AcO─, H2PO42─, S2─). Upon addition of these ions,
there were no significant fluorescence intensity changes, while the
fluorescence intensity in the presence of Hg2+ (5.0 × 10-4 M) obviously
increased at 550 nm with the color changes from pale blue to yellow
green. Meanwhile, the other competing species could hardly interfere
the detection of Hg2+ in a complex environment (Fig. 4b). Under the
day-light and 365 UV-light, the competing species did not produce any
dramatic color changes and “turn-on” fluorescent emission except Hg2+
(Fig. 4c). The results confirmed that the probe P1 is a specific “turn-on”
3.3. Sensitivity of probe P1 to Hg2+
The fluorescence responses of probe P1 to Hg2+ were investigated by
titration experiments in CH3OH/PBS (8:2, v/v, pH = 7.4, 10 mM) so-
lution, and the results were shown in Fig. 3a. With the increasing of
fluorescent probe for detecting Hg2+
.
4

S. Ruan et al.
Inorganic Chemistry Communications 132 (2021) 108847
Scheme 2. Sensing mechanism of P1.
Fig. 5. The optimized geometric structures and corresponding LUMO and HOMO of P1 and P1-CHO by DFT calculation.
3.5. Sensing mechanisms of probe P1 to Hg2+
3.6. Density functional theory (DFT) calculations
Based on the fluorescence intensities of probe P1 in the presence or
absence of Hg2+, the detection mechanism was speculated that the
desulfurization reaction of probe P1 was promoted by Hg2+. The mo-
lecular ion peaks of probe P1 before and after adding Hg2+ were
440.1019 [Fig. S7, P1-Cl, Exact Mass: 440.0985] and 350.1030 [Fig. S8,
P1-CHO-Cl, Exact Mass: 350.1023]. In addition, 1H NMR titration of
probe P1 with Hg2+ can be carried out, and these two methods indicated
that detection mechanism of probe P1 was the same with the postulated
shown in Scheme 2 [33–36].
To further understand the photophysical responses of probe P1 to
Hg2+, DFT calculations were carried out with the Gaussian 09 software
package. The optimized geometric structures and corresponding LUMO
(the lowest unoccupied molecular orbitals) and HOMO (the highest
occupied molecular orbitals) were presented. As shown in Fig. 5, the
HOMO of probe P1 was mainly localized on the hydroxyl group and part
of the D ring. However, its LUMO was evenly distributed in the C and D
rings, which indicated that there was a weak ICT effect in this molecule.
Upon addition of Hg2+, the HOMO of compound P1-CHO was localized
on the hydroxyl group. However, the LOMO was distributed in the
aldehyde group and D rings, indicating a strong ICT effect. In addition,
5

S. Ruan et al.
Inorganic Chemistry Communications 132 (2021) 108847
increased from 0 μM to 500 μM, the fluorescence emission of test paper
450
400
350
300
250
200
strips gradually changed from blue to faint-yellow. Therefore, the probe
P1 could successfully applied to detect Hg2+ on test paper.
3.8. Quantitation of Hg2+ contamination in real water samples
Probe P1 could also be used to detect Hg2+ in two real water samples
collected from Zhangjiang river and Poyang lake. The water samples
were mixed with CH3OH (80%) solutions containing the probe P1 (2.5
× 10-4 M). The various concentrations of Hg2+ solution (0, 50, 100, 150,
200, 250 μM) were added into experimental water samples respectively.
The fluorescence intensity of the experimental samples was measured
using a fluorescence spectrophotometer. As shown in Fig. 7, two good
linear relationships were obtained, and the detection limit for Hg2+ was
0
100
[Hg2+]
200
300
400
500
calculated to be 6.3 μM and 4.4 μM, indicating that the probe P1 can be
applied to detect Hg2+ in real samples.
-6
10 mol/L)
(
Fig. 6. Test-paper experiments of P1 with the different concentrations of Hg2+
4. Conclusion
(0 μM to 500 μM).
In summary, the probe P1 for detecting Hg2+ was synthesized from
berberine. This probe could identify Hg2+ in CH3OH/PBS (8:2, v/v, pH
= 7.4, 10 mM) solution by the obvious color changes at daylight and the
perfect fluorescence changes under 365 nm UV lamp. The probe P1
displayed high selectivity, superior sensitivity, and fast response toward
Hg2+ with a low detection limit and a wide pH range. The probe P1 can
provide a convenient and effective way for Hg2+ detection by virtue of
test paper strips. Moreover, this probe can be also applied to monitor
Hg2+ in real environmental water samples.
the energy gap between HOMO and LUMO of compound P1-CHO was
calculated to be 3.14 eV, which is lower than the probe P1 (3.17 eV).
The result also indicated that the sensing mechanism was shown in
Scheme 2.
3.7. Visualization of Hg2+ in solution by test paper
To investigate the practical application of probe P1 as an on-situ
detection kit for the detection of Hg2+, the test paper experiments
were explored. As shown in Fig. 6, as the concentrations of Hg2+
(b)400
(a)
Poyang Lake
Zhangjiang River
350
350
y = 0.7324 x + 149.4971
y = 1.0443 x + 122.3977
2
300
2
300
250
200
150
R
= 0.99
R
= 0.98
250
200
150
0
50
100
150
200
250
0
50
100
150
200
250
300
[Hg2+]
(
2+
-6
-6
10 mol/L)
[Hg ] (10 mol/L)
(c)
400
300
200
100
0
Poyang Lake
Zhangjiang River
0
50
100
150
200
250
2+
-6
[Hg ] (10 mol/L)
Fig. 7. (a) The linear relationship of fluorescence intensity of P1 and different concentrations of Hg2+ in Zhangjiang river (λem = 550 nm). (b) The linear relationship
of fluorescence intensity of P1 and different concentrations of Hg2+ in Poyang lake (λem = 550 nm). (c) The fluorescence intensity of P1 (2.5 × 10-4 M) towards
different concentration of Hg2+ (0, 50, 100, 150, 200, 250
μM) (λem = 550 nm).
6

S. Ruan et al.
Inorganic Chemistry Communications 132 (2021) 108847
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CRediT authorship contribution statement
Shutang Ruan: Conceptualization, Data curation, Methodology,
Writing – original draft. Yan Zhang: Formal analysis, Resources. Suz-
hen Wu: Investigation. Yu Gao: Investigation. Lijuan Yang: Resources.
Mingxin Li: Software. Yiqin Yang: Supervision. Zhonglong Wang:
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Appendix A. Supplementary material
Supplementary data to this article can be found online at https://doi.
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