A new turn-on fluorescent probe for the detection of palladium(0) and its application in living cells and zebrafish

Article abstract of DOI:10.1039/C8NJ04438D

A new “turn-on” fluorescent probe 1 for the detection of Pd⁰ has been designed and synthesized. The probe possesses potent selectivity to Pd⁰ and can respond quickly to changes in Pd⁰. In addition, the mechanisms of the re

Full text of DOI:10.1039/C8NJ04438D

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A new turn-on fluorescent probe for the
detection of palladium(0) and its application in
Cite this: New J. Chem., 2019,
living cells and zebrafish†
4
3, 548
Received 31st August 2018,
Accepted 13th October 2018
a
a
b
a
c
Ming Jin, Lihong Wei, Yutao Yang,* Mingtao Run and Caixia Yin
*
DOI: 10.1039/c8nj04438d
rsc.li/njc
0
A new ‘‘turn-on’’ fluorescent probe 1 for the detection of Pd has Hence, it is essential to develop sensitive and selective methods
been designed and synthesized. The probe possesses potent selec- for the detection and determination of palladium in the environ-
0
0
tivity to Pd and can respond quickly to changes in Pd . In addition, ment as well as in living systems.
the mechanisms of the reactions were studied and the product of
To date, some traditional analytical methods, including
0
19
20
the probe with Pd was separated. Moreover, the probe can be used X-ray fluorescence, atomic absorption spectroscopy (AAS),
0
21
to sense Pd in BT-474 cells and zebrafish.
coupled plasma mass spectrometry (ICP-MS) and so on, have
been widely used to detect palladium species. But all of these
Palladium, an important noble metal, is of current interest in methods require expensive instrumentation, rigorous experi-
catalytic converters, dental crowns, jewellery, and fuel cells in mental conditions and highly skilled individuals. Contrary to
1
–4
view of its excellent photophysical and chemical properties.
these traditional methods, fluorescent probes, with the unique
Importantly, palladium-catalyzed reactions are increasingly ability to generate a florescence reporter in situ upon reaction
appealing owing to its unique advantages in catalyzing the with palladium species, possess several appealing advantages
formation of difficult bonds and it also serves as an irreplaceable such as simplicity in operating, low cost, high selectivity and
2
2–39
catalyst involved in the synthesis of multiple pharmaceutical sensitivity, non-destructive and in situ analysis, and so on.
5
–9
drugs.
However, in sharp contrast to its favorable effects, Moreover, to the best of our knowledge, a variety of fluorescent
0
0
palladium, which is capable of binding tightly to sulfur- probes for Pd have been synthesized mainly based on the Pd -
4
0–42
containing amino acids, proteins, RNA, DNA, and other bio- catalyzed Tsuji–Trost allylic oxidative insertion reaction.
molecules, can also disturb various physiological processes and
Herein, we developed a new fluorescent probe 1 for the
1
0–15
0
thus can bring about diverse health hazards.
Worryingly, selective detection of Pd , with an allyl carbonate moiety as the
0
with the increasingly wide use of palladium, the resulting high recognition site for Pd and a coumarin derivative as the fluo-
level of Pd residue has raised great concern. Hence, govern- rescent group. On the basis of previously reported research,
3
8–40
ments are imposing increasingly severe limits on the level of the reaction mechanism was attributed to the high specificity
0
residual palladium in final products, with the threshold being of the Pd -triggered cleavage process and the detailed reaction
strictly controlled to 5–10 ppm and the daily intake being no more mechanism is shown in Scheme 1. The free probe is non-
0
than 1.5–15 mg per person per day according to the European fluorescent and immediately reacted with Pd , and this probe
1
6–18
0
Agency for the Evaluation of Medicinal Products (EMEA).
underwent Pd -triggered elimination, resulting in the release of
a
National Experimental Teaching Demostration Center of Chemistry,
College of Chemistry & Environmental Science, Hebei University, Baoding 071002,
P. R. China
b
c
Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of
Education, College of Chemistry & Environmental Science, Hebei University,
Baoding 071002, P. R. China. E-mail: yutaoyang2016@163.com
Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of
Education, Key Laboratory of Materials for Energy Conversion and Storage of
Shanxi Province, Institute of Molecular Science, Shanxi University,
Taiyuan 030006, China. E-mail: yincx@sxu.edu.cn
†
Electronic supplementary information (ESI) available. See DOI: 10.1039/
c8nj04438d
Scheme 1 Proposed sensing mechanism.
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48 | New J. Chem., 2019, 43, 548--551
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the fluorophore and thus recovery of the orange fluorescence. And
The synthetic methods associated with the probe are sum-
1
the reaction mechanism was confirmed by the H NMR spectrum marized in Scheme 2, and the details are in the ESI† (Fig. S1).
and HR-MS data of an isolated reaction product of probe 1 with We investigated the optical sensing properties of probe 1 for
0
0
Pd (Fig. S1, ESI†). UV-vis absorption and fluorescence spectra Pd in EtOH-PBS buffer solution (2: 3, v/v, 10 mM PBS, pH = 7.4).
0
were further used to investigate its optical properties and the Initially, the reaction time of probe 1 with Pd was investigated
0
results indicated that probe 1 possessed a turn-on fluorescence (Fig. 1). Pd (40 mM) was added to an EtOH–PBS buffer (2 : 3, v/v,
0
response to Pd (6-fold). Moreover, the probe can penetrate cell 10 mM PBS, pH = 7.4) solution containing probe 1 (5 mM),
0
membranes and react with Pd within BT-474 cells and zebrafish. leading to a gradual increase of the absorption at 348 nm and
the enhancement of the fluorescence intensity at 560 nm. The
UV absorption and fluorescence spectrum reached a plateau
within 10 minutes, implying that the reaction rate of probe 1
Methods/experimental section
0
towards Pd was very fast (Fig. 1).
All animal procedures were performed in accordance with the
Subsequently, the UV-vis and fluorescence titration experiments
Guidelines for Care and Use of Laboratory Animals at the were performed. As shown in Fig. 1, the UV absorption peaks were
Academy of Military Medical Science animals (SYXK-2014-001) mainly concentrated at 473 nm and 324 nm. With the addition
0
and experiments were approved by the Animal Ethics Committee of Pd (0–40 mM), an ultraviolet absorption peak was almost
of Academy of Military Medical Science.
unchanged at 473 nm and the appearance of a new absorption
peak gradually increased at 348 nm, accompanying the color of the
solution changing from light yellow to yellowish brown. Corre-
spondingly, probe 1 is almost non-fluorescent (fluorescence quan-
0
tum yield: 0.0095), the addition of Pd also caused the enhancement
of the fluorescence intensity of 560 nm (the fluorescence quantum
yield of the product: 0.28) and the detection limit was 4.18 mM based
on the IUPAC method (Fig. 2 and Fig. S2, ESI†).
Moreover, the selectivity and competition of probe 1 towards
0
Scheme 2 Synthesis of probe 1.
Pd were also investigated (Fig. 3). By the addition of various
+
3+
+
2+
+
2+
metal ions (200 mM), including Ag , Ce , K , Ni , Na , Mn ,
Fig. 1 Top: Time dependent UV-vis absorbance spectra upon addition of
Pd in ethanol–PBS buffer solution (2 : 3, v/v, 10 mM PBS, pH = 7.4) (inset:
0
0
Fig. 2 Top: Absorption spectra of probe 1 (5 mM) upon addition of Pd
time dependent absorbance spectra of probe 1 (5 mM) upon addition of
(40 mM) in ethanol–PBS buffer solution (2 : 3, v/v, 10 mM PBS, and pH = 7.4)
0
0
Pd (40 mM) at 348 nm); bottom: time dependent fluorescence spectra
(inset: color changes of the solution of 1 upon addition of Pd ); bottom:
0
0
upon addition of Pd in ethanol–PBS buffer solution (2 : 3, v/v, 10 mM PBS,
fluorescence spectra of probe 1 (5 mM) upon addition of Pd (40 mM) in
and pH = 7.4) (lex = 450 nm, slit: 5 nm/5 nm) (inset: time dependent
fluorescence intensity of probe 1 upon addition of Pd (40 mM) at 560 nm).
ethanol–PBS buffer solution (2 : 3, v/v, 10 mM PBS, and pH = 7.4) (inset:
0
0
fluorescence changes of the solution of 1 upon addition of Pd ).
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Fig. 4 Effect of pH on the fluorescence intensity at 560 nm of probe 1
0
upon addition of Pd .
0
Fig. 3 Top: Fluorescence spectra of probe 1 (5 mM) in the presence of Pd
+
3+
+
2+
+
2+
2+
2+
(
40 mM) and other metal ions (Ag , Ce , K , Ni , Na , Mn , Mg , Ca ,
2+
2+
3+
2+
2+
3+
3+
2+
2+
Hg , pb , Fe , Cd , Zn , Cr , Al , Cu and Co ) (200 mM) in
ethanol–PBS buffer solution (2 : 3, v/v, 10 mM PBS, and pH = 7.4) (lex
50 nm, slits: 5 nm/5 nm); bottom: fluorescence spectra of probe 1 (5 mM)
in ethanol–PBS buffer solution with various relevant species (200 mM):
=
4
+
+
3+
3+
(
(
1) none; (2) Pd(0); (3) Ag ; (4) Ag + Pd(0); (5) Ce ; (6) Ce + Pd(0);
2+
2+
2+
2+
2+
2+
7) Mn ; (8) Mn + Pd(0); (9) Mg ; (10) Mg + Pd(0); (11) Ca ; (12) Ca
+
+
2+
2+
+
+
Pd(0); (13) Hg ; (14) Hg + Pd(0); (15) K ; (16) K + Pd(0); (17) Na ;
+
3+
3+
2+
2+
(
18) Na + Pd(0); (19) Fe ; (20) Fe + Pd(0); (21) Zn ; (22) Zn + Pd(0);
2+
2+
2+
2+
2+
2+
(
23) Cd ; (24) Cd + Pd(0);(25) Ni ; (26) Ni + Pd(0); (27) Pb ; (28) Pb
+
3+
3+
3+
3+
2+
Pd(0); (29) Cr ; (30) Cr + Pd(0); (31) Al ; (32) Al + Pd(0); (33) Cu
;
2
+
2+
2+
Fig. 5 Confocal fluorescence images of probe 1 in BT-474 cells. Top:
(
44) Cu + Pd(0); (35) Co ; (36) Co + Pd(0).
(
A) BT-474 cells were incubated with probe 1 (10 mM) for 0.5 h, (B–D) BT-474
0
cells were incubated with Pd (20, 40, and 100 mM) for 0.5 h and then with
2+
2+
2+
2+
3+
2+
2+
3+
3+
2+
2+
probe 1 (10 mM) for another 0.5 h; (emission was observed at 493–591 nm
Mg , Ca , Hg , pb , Fe , Cd , Zn , Cr , Al , Cu and Co ,
there was no obvious change in the fluorescence spectrum.
(
excited at 458 nm, scale bar: 40 mm)); bottom: fluorescence intensity of A,
B, C, and D.
However, the fluorescence intensity was increased observably at
0
5
60 nm after the addition of Pd (40 mM). Accordingly, absorption
spectra have been studied (Fig. S4, ESI†). Meanwhile, anions did
0
not interfere with the detection of Pd (Fig. S5, ESI†). These
0
results showed that probe 1 has good selectivity for Pd .
Besides, the effect of pH was also studied; Fig. 4 shows that
probe 1 was stable in the pH range of 3–12. Upon addition of
0
Pd , the fluorescence intensity at 560 nm was increased signifi-
cantly at pH values ranging from 5 to 10, suggesting that probe
0
1
can be applied to the detection of Pd in biological systems.
Encouraged by the results of the above research, the appli-
0
cability of probe 1 to image Pd was further investigated. MTT
assay results indicated that 20 mM of probe 1 had little effect on
BT-474 cell growth after 12 h (Fig. S6, ESI†). Hence, we studied
Fig. 6 Confocal fluorescence images of the probe with different con-
centrations of Pd (0, 40, and 100 mM) in zebrafish (emission was observed
at 493–591 nm (excited at 458 nm, scale bar: 500 mm)).
0
0
the detection of Pd in living cells. BT-474 cells were incubated
with probe 1 (10 mM) for 0.5 h and weak fluorescence was
observed (Fig. 5A). When BT-474 cells were incubated with 10,
0
4
0, and 100 mM of Pd for 0.5 h, and then incubated with 10 mM fluorescence was respectively observed (Fig. 5B–D). The results
0
of probe 1 for another 0.5 h, a remarkable enhancement of showed that probe 1 could detect Pd in living cells.
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0
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0
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0
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19 K. Van Meel, A. Smekens, M. Behets, P. Kazandjian and
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0
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Conflicts of interest
There are no conflicts to declare.
Acknowledgements
This research was supported by the National Natural Science
Foundation of China (21807021, 21672131, 21775096, and
21705102), the Hebei University Science Foundation for High-
level personnel (1081-801260201024) and the Hebei Province
Natural Science Foundation for Youths (No. B2017201093).
We also acknowledge the Teaching Reform Project of Hebei
University (HBUHXJG2016-16).
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