A two-photon ratiometric ESIPT probe for fast detection and bioimaging of palladium species

Article abstract of DOI:10.1039/c7ob01189j

A novel ratiometric ESIPT fluorescent probe, which is specific for palladium species of all the typical oxidation states (0, +2, and +4), has been designed. Notably, based on the excited state intramolecular proton transfer (ESIPT) process, the probe exhibits a ratiometric fluorescent response to palladium species with a low detection limit (9.0 nM, 0.96 ppb) in about 1.5 min at room temperature. Moreover, it has been successfully used as a two-photon ratiometric fluorescent palladium probe for in vivo and three-dimensional imaging with low cytotoxicity and autofluorescence. Compared with other reported palladium probes, the probe displays a shorter ratiometric response time and lower detection limit in milder test conditions. All of the results indicate that the probe may be favorable for environmental and biological applications.

Full text of DOI:10.1039/c7ob01189j

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: W. Luo, J. Li and .
, Org. Biomol. Chem., 2017, DOI: 10.1039/C7OB01189J.
This is an Accepted Manuscript, which has been through the
Volume 14 Number
1 7 January 2016 Pages 1–372
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
www.rsc.org/obc
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 1 of 6
View Article Online
DOI: 10.1039/C7OB01189J
Journal Name
ARTICLE
A Two-Photon Ratiometric ESIPT Probe for Fast Detection and
Bioimaging of Palladium Species
Received 00th January 20xx,
Accepted 00th January 20xx
Weifang Luo, Jing Li and Weisheng Liu*
A novel ratiometric ESIPT fluorescent probe specific for palladium species of all the typical oxidation states (0, +2, +4) has
been designed. Notably, based on the excited state intramolecular proton transfer (ESIPT) process, the probe exhibits
ratiometric fluorescent response towards palladium species in about 1.5 min at room temperature with a low detection
limit (9.0 nM, 0.96 ppb). Moreover, it has been successfully used as a two-photon ratiometric fluorescence palladium
probe for vivo and three-dimensional imaging with low cytotoxicity and autofluorescence. Compared with other reported
palladium probes, the probe owns shorter ratiometric response time and lower detection limit in more mild test condition.
All the results indicate that the probe may be favorable for environmental and biological applications.
sensitivity and bioimaging.6 Until now, various palladium
DOI: 10.1039/x0xx00000x
www.rsc.org/
1. Introduction
fluorescent probes have been reported. Compared with
chemosensors,7 chemodosimeters based on specific catalytic
With the increasing concern of human health and
environmental pollution, the resulting active research on the
potential impact of palladium ions since its wide application in
synthesis, pharmacy and various materials, such as catalysts,
medical instruments, dental alloys, fuel cells, electronics and
jewelry.1 Moreover, palladium can be bound to proteins, DNA,
and other biomolecules, which disturbs a variety of biological
processes through the biological effects of palladium, including
toxicity, allergenicity, carcinogenicity and therapeutic effects.2
However, intracellular palladium is emerging as an exogenous
metal that is of interest in recent years for those involved in
BOOM chemistry (to unmask bioactive compounds upon the
addition of palladium) and drug delivery.3 By the way,
governmental regulations on the levels of palladium in end
products are very strict, its threshold in drugs is 5–10 ppm and
the proposed dietary intake is 1.5−15 ug per person per day.4
Therefore, effective assay methods to monitor low level and
intracellular palladium species are urgently needed.
mechanism (i.e., oxidative cyclization reaction, Tsuji-Trost
reaction)8 have attracted more attention for the excellent
selectivity. Nevertheless, they are far from ideal. Generally,
most palladium probes are OFF-ON or ON-OFF signal output
changes only in fluorescence intensity, in which quantitative
detection could be significantly influenced by environmental
effects, along with a decrease in signal fidelity.9 In contrast,
ratiometric fluorescent probes own the permitting signal
rationing feature, which can increase the dynamic range and
provide built-in correction for environmental effects, thereby
detecting the analyte more accurately.6d,10 Moreover, many of
the reported probes work in a high proportion of organic
solvent and require extended reaction time at elevated
temperature, which all limit their practical application in
environmental detection and biological imaging.11 In addition,
two-photon excitation fluorescence (TPEF) imaging for living
cells and tissues owns remarkable advantages over one-
photon microscopy (OPM), such as increased penetration
depth, prolonged observation time, low autofluorescence
levels, reduced phototoxicity and three-dimensional imaging
of living tissues.12 However, palladium probes developed on
two-photon fluorescence have rarely been reported up to
now.13
In contrast to the typical analytical methods such as plasma
emission methods (e.g., ICP-MS and ICP-AES), atomic
absorption spectroscopy (AAS), and X-ray fluorescence,5 which
are all still a challenge for the rational design of palladium
probes, especially for detecting the presence and imaging in
living systems, fluorimetric analytical approach would be more
desirable for the undamage, simple operation, low cost, high
In the investigation described below,
a two-photon
ratiometric reaction-based fluorescent palladium probe has
been designed for meeting the criteria of both bioimaging and
quantitative detection in PBS buffer solution (pH = 7.4,
containing 10% THF). The design strategy relies on a specific
Pd-triggered cleavage process, the terminal allyl chloroformat
acts as a recognition site, then the ESIPT process between
hydroxy and the O atom of ketene is recovered after treating
with palladium. And the fluorophore is 3-hydroxylflavone
derivative, which has a large Stokes’ shift (>150 nm) owing to
a. a.Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of
Gansu Province and State Key Laboratory of Applied Organic Chemistry, College
of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, P.
R. China
b. * Corresponding authors. Tel: +86 931 8915151; fax: +86 931 8912582
c. E-mail addresses: liuws@lzu.edu.cn (W. S. Liu)
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 6
ARTICLE
Journal Name
the ESIPT process of the part of 3-hydroxylflavone under presence of other metal ions (Fig. S2a). MoreoVvieewr,ArdticiflefeOrnelinnet
photoexcitation through rapid photoinduced proton transfer anion-induced influences on the sensinDgObI:e1h0a.1v0i3o9r/Cw7OeBre011a8l9sJo
resulting tautomerization, leading to a dual emission.6d,10e investigated, showing hardly experienced interference from
2-
-
-
Compared with earlier works, the key factors were that the commonly anions, such as CO3 , Br-, SO42-, NO3 , AcO2 , SCN-, I-
probe exhibited ratiometric fluorescent response specific to and F-. That is,
owned a good sensitivity and selectivity
1
palladium species (0, +2, +4) in about 1.5 min at room towards Pd0 over other ions.
temperature. Moreover, the probe owns a low detection limit
(9.0 nM, 0.96 ppb) under test conditions. Furthermore,
1 could
be certified as a two-photon ratiometric palladium probe for
bioimaging.
2. Results and discussion
2.1. Fluorescence response toward palladium
The spectroscopic properties of probe 1 were rated in PBS buffer
solution (pH = 7.4, containing 10% THF) at room temperature,
which owned faster and stronger response than in water (Figure S1).
First, the fluorescent spectroscopic properties of 1 were studied. 1
exhibited fluorescence emission of 470 nm (Φ = 0.019) upon
excitation at 380 nm. After treatment with palladium, the emission
at 470 nm decreased rapidly with a new band at 552 nm appearing
Fig. 2. a) Fluorescence responses of
1
1 (10 μM) to palladium sources (5 equiv.); b)
Metal ion selectivity of in PBS buffer solution (pH = 7.4, containing 10% THF).
2.3. Sensing mechanism and fluorescence titration
The excellent selectivity should be owing to the specific Pd0-
triggered cleavage process.15 Kinetic study was firstly carried
out, which showed that the reaction between
accorded with 1:1 stoichiometry (Fig. 3a). Thus, a feasible
1
and Pd0
(Φ = 0.015), which created an isosbestic point at 520 nm and mechanism could be explained by the procedure in Scheme 1.
It is expected that the triggermoiety of allyl chloroformate unit
is initially conjugated with Pd0 and then the compound is
exhibited a ratiometric response. The remarkable red shift is due to
the ESIPT process. The time-dependent emission spectra changes of
1 monitoring by the fluorescence intensity ratio I552 nm/I470 nm
were also investigated. The result showed that the fluorescence
saturation of 1 with palladium (1 equiv.) reached equilibrium only
took 1.5 min (Fig. 1b).
ionized to form
3
, further dissociates π -allylpalladium(II) to
, which
produce 4, finally decarboxylaes to transform into
2
corresponded to the peak at m/z 282.0 in mass spectrum (Fig.
S10) and confirmed this mechanism further.
Fig. 1. a) Fluorescence spectral changes of
1 (10 μ M) upon treatment with
Pd(PPh3)4 (10 μ M) with micromolar NaBH4 in PBS buffer solution (pH = 7.4,
containing 10% THF). λex = 380 nm. Slit: 5.0 nm/5.0 nm; b) The time-dependent
fluorescence changes acquired in 20 min.
2.2. Ion selectivity and competitiveness
To explore the reactivity of probe
1 toward other oxidation
states of palladium metal sources, PdCl2, Pd(PPh3)2Cl2,
Pd2(dba)3, (C3H5)2PdCl2 and K2PdCl6 were examined (Fig. 2a). To
Scheme 1. Sensing mechanism of probe 1 for selective recognition of palladium.
our delight, Pd2+ and Pd4+ exhibited similar response to probe
as Pd0 under the same test conditions. In other words, probe
1
1
Since most of the Pd-catalysts are in Pd0 state, such as
Pd(PPh3)4, which is used in many reactions frequently and
fruitfully. It seems that the detection of Pd0 in the
environment and living systems is more necessary and
pressing,16 for a large amount of residual palladium (300-2000
ppm) is often found in the resultant products, leading to
serious human health hazard and environmental pollution.4
could detect all the typical oxidation states (0, +2, +4)
palladium species.
Next, fluorescence responses of probe
1 to other different
metal ions were studied (Fig. 2b). Gratifyingly, the ratiometric
response was detected only in the case of palladium, other
metal species such as Al3+, Na+, K+, Ca2+, Ba2+, Mg2+, Zn2+, Cr3+,
Cd2+, Co2+, Mn2+, Li+, Cu2+, Fe3+, Ni2+, Pb2+, Hg2+, Pt2+ and Au3+
had no or little effect on the emission of probe
1. The
competition experiments also showed a negligible effect in the
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 6
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name ARTICLE
View Article Online
DOI: 10.1039/C7OB01189J
Fig. 3. a) Fluorescence spectra of
PBS buffer solution (pH = 7.4, containing 10% THF), inset: the fluorescence
intensity ratio (I552nm/I470nm) changes of
upon addition of Pd0; b) The linear
relationship of
(10 μM) between Pd0 (0−10 μM) and the fluorescence intensity
1
(10 μM) upon titration with Pd0 (0-20 μM) in
1
1
ratios I552nm/I470nm in PBS buffer solution (pH = 7.4, containing 10% THF).
Upon titration of Pd0 (Fig. 3b), a remarkable ratiometric
fluorescence change could be observed. The fluorescence
intensity ratios of probe 1 (10 μ M) at 470 and 552 nm (I552
nm/I470 nm) increased linearly (R2 = 0.9924) with the amount
of Pd0 (0−10 μM) in PBS buffer solution (pH = 7.4, containing
10% THF) at room temperature. The detection limit of 1
for Pd0
was detected as 9.0 nM (Pd content = 0.96 μ g/L),15c much
lower than the palladium content in persons found from
samples of morning saliva (10.6±7.4 μg/L).4
Fig. 4. Images of HeLa cells incubated with 10 μM
HeLa cells incubated with 5 μM (2) or 10 μM (3) Pd0 and 10 nM NaBH4 for 1h,
then the cells loaded with 10 μ M , the scale bar is 20 μ m. One-photon
fluorescent images (a), excitation at 380 nm. Two-photon fluorescent images (b),
excitation at 760 nm.
1 for 30 min (1); images of
1
2.4. Two-photon properties and its application in bioimaging
2.4.1 Two-photon absorbtion cross section (δ)
Then, we utilized the one/two-photon fluorescence
Considering intracellular palladium is emerging as an microscopy experiment technique to study its higher gradation
exogenous metal that is of interest in recent years for those of application in complex biological systems. Data in Fig. 4
involved in BOOM chemistry and drug delivery, detecting Pd0 showed that after incubated the cells with 10 μM
in the living systems becomes very important. Firstly, the in a CO2 incubator, it exhibited blue fluorescence when
1 for 30 min
fluorescence response of probe
pH was studied, indicating that
1
to palladium under different induced by whether OP or TP excitation light source. As
and (10 μ M) and further
-Pd0 conform with the expected, cells pre-treated with
1
1
1
ratiometric fluorescence change in wide pH ranges (pH 4-11) incubated with Pd0 (5 μM or 10 μM) displayed that the blue
(Fig. S3), which within the biological relevant pH range (7.07- fluorescence weakened and the green fluorescence enhanced,
7.93).17 That is,
biological system wonderfully. Then, the two-photon (TP) cross Fgreen/Fblue increased with the Pd0 concentration increasing.
sections of and
-Pd0 were measured to confirm the Moreover, better than OP imaging, TP imaging exhibited low
potential application of probe for TPEF imaging. As shown in autofluorescence and high resolution.
Fig. S4, owns enlarged TP cross sections after treating with
Pd0, it’s δmax value is 148 GM at 760 nm, and -Pd0 is 271 GM
at 790 nm. The results indicated that was very satisfied to be
1 could be applied for palladium detection in showing a ratiometric fluorescence change. And the ratio of
1
1
1
1
1
1
a TP fluorescence palladium probe in the living systems for
enlarged cross sections.
2.4.2 Cell cytotoxicity
To further investigate the usefulness of
1 to image the
palladium species in living systems, HeLa cells were chosen for
its application in vivo. Firstly, we studied the cell viability using
the MTT assay, which shown that although the concentration
of
1 and 1
-Pd0 were all up to 100 μM, the viability of HeLa cells
was still over 60% (Fig. S5a). And we selected the testing
amount was 10 μM, which just had negligible toxicity to the
cells.
2.4.3 Fluorescence imaging
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 4 of 6
ARTICLE
Journal Name
Furthermore,
1
can be used as a TP ratiometricVfielwuoArrteicslecOennlicnee
DOI: 10.1039/C7OB01189J
palladium probe for bioimaging of vivo and three-dimensional
with low cytotoxicity and autofluorescence.
4. Experimental section
4.1. Materials and general methods
Unless otherwise noted, all reagents and solvents were
obtained commercially and used without further purification
unless otherwise noted. All animal experiments were performed
in compliance with the relevant laws and institutional
guidelines issued by the Ethical Committee of Lanzhou
University. Mass spectra (ESI) were performed on a LQC
system (Finngan MAT, USA). High resolution mass spectrum
1
(HRMS) were measured on a maXis 4G. H NMR and 13C
NMR spectra were recorded on
a
JEOLBCS 400M
spectrometer and referenced to the solvent signals. The melting
points were measured on an X-6 melting point apparatus
without calibration (Beijing Fuka Keyi Science and Technology
Co., LTD). One-photon fluorescence spectra were recorded
using
a Hitachi F-7000 spectrofluorometer. Two-photon
fluorescence spectra were measured using an Edinburgh
FLSP920. HeLa cells were procured from the biomedical
engineering center of Lanzhou University (Lanzhou, China).
Tissue slices were prepared from Hela cancer cells.
Fluorescence images of HeLa cells and tissues were obtained
using an Olympus FV1000 laser confocal microscope IΧ81.
Fig. 5. The confocal fluorescence imaging of a part of a fresh thick cervicaltissue
slice stained by 1. (A) Z-scan OPE (OPFI) and (B) TPE (TPFI) fluorescence images at
4.2. Synthesis preparation of probe 1
different penetration depths, the scale bar is 200 μm; (C) Bright-field image (a),
TPE fluorescence blue (b) and green (c) channel image, overlay image (d) and the
3D reconstruction from 11 confocal Z-scan TPE imaging sections at depth of 0-
400 μm with 10×magnification, the scale bar is 200 μm (e,D).
Probe
1 was obtained by the synthetic route (Scheme S1), in
which compound
procedure.14
2
was synthesized according to the literature
Synthesis of probe
1
. To a solution of 2 (200 mg, 0.55 mmol)
The fluorescence images experiments of labeled tissues were
also studied, which wonderfully proved that the penetration
depth of TP is deeper than that of OP. As shown in Fig. 5, when
and allyl chloroformate (0.5 mL) in dry DMF (80 mL) at 0 °C,
triethylamine (111 mg, 1.1 mmol) was added dropwise and
kept stirring at 0 °C for 30 min. Then the mixture was warmed
to room temperature and stirred another 4 h. After
completion of the reaction, the mixture was concentrated
under vacuum to get the crude product. Then the crude
product was dissolved in trichloromethane and washed with
water and brine, dried with Na2SO4. The concentrated residue
certain concentration of
1 was added into the tissues, strong
blue fluorescence occurred under excited by whether OP or TP.
Then, another Pd0 was added into the tissues, a new green
fluorescence appeared, showing a ratiometric fluorescence
change. Moreover, the penetration depth of blue fluorescence
from TP fluorescence microscope could reach to 250 μ m at
least; however, it was only up to 150 μm from OP fluorescence
was purified by column chromatography to afford 1. Yield:
1
92.7 mg, (60%). M.p. 88.4-89.3 °C. H NMR (400 MHz, DMSO-
d6) δ 8.03 (dd, J = 8.0, 1.5 Hz, 1 H), 7.83 – 7.73 (m, 4 H), 7.52 –
7.46 (m, 1 H), 6.83 (d, J = 9.2 Hz, 2 H), 5.94 (ddt, J = 17.2, 10.6,
5.4 Hz, 1 H), 5.38 (dq, J = 17.3, 1.6 Hz, 1 H), 5.27 (dq, J= 10.6,
1.3 Hz, 1 H), 4.71 (dt, J = 5.4, 1.4 Hz, 2 H), 3.01 (s, 6 H). 13C NMR
(100 MHz, DMSO-d6) δ 171.13, 156.69, 155.27, 152.69, 152.30,
134.82, 132.10, 132.08, 132.02, 129.99, 125.94, 125.41, 123.29,
119.16, 118.94, 115.25, 112.02, 69.68, 55.45. MS (ESI)
calculated for C21H20NO5+ (M + H+) 366.13, found 366.12. HRMS
microscope. Above all, the satisfactory results indicated that
1
could penetrate the cell membrane and enable imaging of Pd0
with an obvious ratiometric fluorescence change in the living
cells and tissues.
3. Conclusions
In conclusion, we have rationally developed
a novel
ratiometric ESIPT fluorescent palladium probe based on the
Pd0-triggered cleavage reaction. The probe displays specific
and ratiometric fluorescent response towards palladium
species of all the typical oxidation states (0, +2, +4) in about
1.5 min at room temperature. Moreover, the probe owns a
remarkable detection limit as low as 9.0 nM (0.96 ppb).
(ESI) calculated for C21H20NO5 (M + H+) 366.1341, found
+
366.1338.
Acknowledgements
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 6
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name ARTICLE
Kim, J. Cui, X. Qian, D. Spring, I. Shin and J. Yoon, J. Am. Chem.
Soc., 2009, 132, 601; (e) T. Gao, P. Xu,DMOI.: L10iu.1,0A39. /BCi7,OPB.0H11u8,9BJ.
Ye, W. Wang and W. Zeng, Chem.-An Asian J., 2015, 10, 1142.
This study was supported by the NSFC (Grant 21431002) and
the Fundamental Research Funds for the Central Universities
(lzujbky-2015-k04).
View Article Online
11 (a) L. Duan, Y. Xu and X. Qian, Chem. Commun., 2008, 47
,
6339; (b) B. Liu, Y. Bao, F. Du, H. Wang, J. Tian and R. Bai,
Chem. Commun., 2011, 47, 1731; (c) F. Lu, M. Yamamura and
T. Nabeshima, Dalton Trans., 2013, 42, 12093; (d) A. K. Atta,
S.-B. Kim, J. Heo and D.-G. Cho, Org. Lett., 2013, 15, 1072.
Notes and references
1
(a) R. F. Heck, Palladium eagents in Organic Syntheses,
Academic Press, New York, 1985; (b) J. Le Bars, U. Specht, J. S.
Bradley and D. G. Blackmond, Langmuir, 1999, 15, 7621; (c) L.
F. Tietze, H. Ila and H. P. Bell, Chem. Rev., 2004, 104, 3453; (d)
S. MacQuarrie, J. H. Horton, J. Barnes, K. McEleney, H.-P.
12 (a) W. Denk, J. Strickler and W. W. Webb, Science, 1990, 248
73; (b) H. M. Kim, C. Jung, B. R. Kim, S.-Y. Jung, J. H. Hong, Y.-
,
G. Ko, K. J. Lee and B. R. Cho, Angew. Chem. Int. Ed., 2007, 46
3460; (c) X. Zhang, X.-J. Huang and Z.-J. Zhu, RSC Adv., 2013,
,
3
Dou, Z. Ju, Z. Li and W. Liu, J. Mater. Chem. B, 2015, , 3459;
, 24891; (d) W. Luo, H. Jiang, K. Zhang, W. Liu, X. Tang, W.
3
Loock and C. M. Crudden, Angew. Chem., Int. Ed., 2008, 47
3279; (e) T. W. Lyons and M. S. Sanford, Chem. Rev., 2010,
110, 1147.
,
(e) Y. H. Lee, W. X. Ren, J. Han, K. Sunwoo, J.-Y. Lim, J.-H. Kim
and J. S. Kim, Chem. Commun., 2015, 51, 14401.
13 (a) H. Cui, H. Chen, Y. Pan and W. Lin, Sens. Actuators B, 2015,
2
3
(a) W. Moore, D. Hysell, L. Hall, K. Campbell and J. Stara,
Environ. Health Perspect., 1975, 10, 63; (b) International
Programme on Chemical Safety. Palladium; Environmental
Health Criteria Series 226; World Health Organization:
Geneva, 2002; (c) C. L. Wiseman and F. Zereini, Sci. Total
Environ., 2009, 407, 2493; (d) J. C. Wataha and C. T. Hanks, J.
Oral Rehabil., 1996, 23, 309.
M. P. Tracey, D. Pham and K. Koide, Chem. Soc. Rev., 2015,
44, 4769.
C. E. Garrett and K. Prasad, Adv. Synth. Catal., 2004, 346, 889.
219, 232; (b) W. Luo and W. Liu, J. Mater. Chem. B, 2016,
3911; (c) W. Luo and W. Liu, Dalton Trans., 2016, 45, 11682.
4
,
14 (a) S. Gunduz, A. C. Goren and T. Ozturk, Org. Lett., 2012, 14,
1576; (b) Z. Song, R. T. K. Kwok, E. Zhao, Z. He, Y. Hong, J. W.
Y. Lam, B. Liu, and B. Z. Tang, ACS Appl. Mater. Interfaces,
2014,
15 (a) Z. Q. Guo, S. Nam, S. Park and J. Yoon, Chem. Sci., 2012,
2760; (b) Z. Q. Guo, G. H. Kim, J. Yoon and J. Shin, Nat.
Protoc., 2014, , 1245; (c) X. Wang, Z. Guo, S. Zhu, H. Tian
and W. Zhu, Chem. Commun., 2014, 50, 13525; (d) K. Xiang, Y.
Liu, C. Li, B. Tian and J. Zhang, RSC Adv., 2015, , 52516.
6, 17245.
3
,
4
5
9
(a) E. H. Evans and J. J. Giglio, J. Anal. At. Spectrom., 1993, 8,
1; (b) L. Bencs, K. Ravindra and R. V. Grieken, Spectrochim.
Acta, Part B, 2003, 58, 1723; (c) B. Dimitrova, K. Benkhedda,
5
16 (a) L. Kurti and B. Czako, Strategic Applications of Named
Reactions in Organic Synthesis, Elsevier Academic Press,
London, 2005; (b) A. L. Garner, F. Song and K. Koide, J. Am.
Chem. Soc., 2009, 131, 5163; (c) A. L. Garner and K. Koide,
E. Ivanova and F. Adams, J. Anal. At. Spectrom., 2004, 19
,
1394; (d) K. Van Meel, A. Smekens, M. Behets, P. Kazandjian
and R. Van Grieken, Anal. Chem., 2007, 79, 6383; (e) H. Li, J.
Fan and X. Peng, Chem. Soc. Rev., 2013, 42, 7943.
Chem. Commun., 2009,
17 W.-T. Gong, B. Gao, J.-Z. Zhao and G.-L. Ning, J. Mater. Chem.
A, 2013, , 5501.
1, 86.
6
(a) H. Huang, K. Wang, W. Tan, D. An, X. Yang, S. Huang, Q.
Zhai, L. Zhou and Y. Jin, Angew. Chem., Int. Ed., 2004, 43
,
1
5635; (b) B. Zhu, C. Gao, B. Du and X. Zhang, Chem. Commun.,
2011, 47, 8656; (c) H. N. Kim, W. X. Ren, J. S. Kim and J. Yoon,
Chem. Soc. Rev., 2012, 41, 3210; (d) B. Liu, H. Wang, T. Wang,
Y. Bao, F. Du, J. Tian, Q. Li and R. Bai, Chem. Commun., 2012,
48, 2867; (e) W. Xuan, C. Sheng, Y. Cao, W. He and W. Wang,
Angew. Chem. Int. Ed., 2012, 51, 2282; (f) S. Sun, B. Qiao, N.
Jiang, J. Wang, S. Zhang and X. Peng, Org. Lett., 2014, 16
,
1132; (g) Z. Yang, J. Cao, Y. He, J. H. Yang, T. Kim, X. Peng and
J. S. Kim, Chem. Soc. Rev., 2014, 43, 4563.
7
8
(a) H. Li, J. Fan, F. Song, H. Zhu, J. Du, S. Sun and X. Peng,
Chem.–Eur. J., 2010, 16, 12349; (b) S. Goswami, D. Sen, N. K.
Das, H. Fun and C. K. Quah, Chem. Commun., 2011, 47, 9101;
(c) H. Kim, K.-S. Moon, S. Shim and J. Tae, Chem. –Asian J.,
2011, 6, 1987; (d) B. Liu, Y. Bao, H. Wang, F. Du, J. Tian, Q. Li,
T. Wang and R. Bai, J. Mater. Chem., 2012, 22, 3555.
(a) F. Song, A. L. Garner and K. Koide, J. Am. Chem. Soc., 2007,
129, 12354; (b) R. J. Houk, K. J. Wallace, H. S. Hewage and E.
V. Anslyn, Tetrahedron, 2008, 64, 8271; (c) M. E. Jun and K. H.
Ahn, Org. Lett., 2010, 12, 2790; (d) J. Jiang, H. Jiang, W. Liu, X.
Tang, X. Zhou, W. Liu and R. Liu, Org. Lett., 2011, 13, 4922; (e)
E. Pershagen, J. Nordholm and K. E. Borbas, J. Am. Chem.
Soc., 2012, 134, 9832; (f) S. Cai, Y. Lu, S. He, F. Wei, L. Zhao
and X. Zeng, Chem. Commun., 2013, 49, 822.
9
(a) R. Hu, J. Feng, D. Hu, S. Wang, S. Li, Y. Li and G. Yang,
Angew. Chem., Int. Ed., 2010, 49, 4915; (b) M. Santra, S. Ko, I.
Shin and K. Ahn, Chem. Commun., 2010, 46, 3964; (c) T.
Schwarze, W. Mickler, P. Saalfrank and H. Holdt, Chem. – Eur.
J., 2010, 16, 1819; (d) X. Yang, Y. Guo and R. M. Strongin,
Angew. Chem., Int. Ed., 2011, 50, 10690; (e) D. Keum, S. Kim
and Y. Kim, Chem. Commun., 2014, 50, 1268.
10 (a) Z. C. Xu, X. H. Qian and J. N. Cui, Org. Lett., 2005, 7, 3029;
(b) A. Ajayaghosh, P. Carol and S. Sreejith, J. Am. Chem. Soc.,
2005, 127, 14962; (c) D. Domaille, W. L. Zeng and C. J. Chang,
J. Am. Chem. Soc., 2010, 132, 1194; (d) Z. Xu, K. H. Baek, H.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Organic & Biomolecular Chemistry
Page 6 of 6
View Article Online
DOI: 10.1039/C7OB01189J
A two-photon ratiometric ESIPT probe specific for fast detection of palladium species and it can
be used for bioimaging