Optical Pd2+ sensing by rhodamine hydrazone ligands: Different stoichiometries in aqueous/nonaqueous environments

Article abstract of DOI:10.1016/j.tetlet.2013.05.094

A series of rhodamine spiro-leuco compounds have been developed as fluorescence-enhanced sensors for optical sensing of palladium ion (Pd ²⁺). The initial rhodamine hydrazone derivatives, RPd1-a, RPd1-b, and RPd1-c, display a good coordination to Pd²⁺ inducing the spirolactam-open reaction with a significant fluorescence enhancement and color generation. Different stoichiometry results, 1:2 in EtOH/H₂O and 1:1 in MeOH/DCM were observed for Pd²⁺/RPd1-c complexation.

Full text of DOI:10.1016/j.tetlet.2013.05.094

Tetrahedron Letters 54 (2013) 4357–4361
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Optical Pd2+ sensing by rhodamine hydrazone ligands: different
stoichiometries in aqueous/nonaqueous environments
⇑
⇑
Honglin Li , Jianfang Cao , Hao Zhu, Jiangli Fan , Xiaojun Peng
State Key Laboratory of Fine Chemicals, Dalian University of Technology, No. 2, Linggong Road, High-tech District, Dalian 116024, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of rhodamine spiro-leuco compounds have been developed as fluorescence-enhanced sensors for
optical sensing of palladium ion (Pd2+). The initial rhodamine hydrazone derivatives, RPd1-a, RPd1-b,
and RPd1-c, display a good coordination to Pd2+ inducing the spirolactam-open reaction with a signifi-
cant fluorescence enhancement and color generation. Different stoichiometry results, 1:2 in EtOH/H2O
and 1:1 in MeOH/DCM were observed for Pd2+/RPd1-c complexation.
Received 23 January 2013
Revised 19 May 2013
Accepted 21 May 2013
Available online 30 May 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Optical sensing
Palladium ion
Rhodamine hydrazone
Selectivity
Stoichiometry
In the past decades, considerable attention has been focused on
the design and synthesis of fluorescent sensors for metal ions be-
cause of their significant importance in chemistry, cellular biology,
and environmental science.1 The analytes have mainly included
the alkali metal ions,2a alkaline earth metal ions,2b heavy- (and in-
ner-) transition-metal (HTM) ions,2c and precious metal ions,3 such
as gold ion, silver ion, and also platinum-group elements ions
(especially Pt4a and Pd4b–f). Pd is one of the platinum-group ele-
ments (PGEs including Pd, Pt, Ru, Rh, Os, and Ir) which are widely
used in various materials such as dental crowns, catalysts,5a fuel
cells, and jewelry. Pd-catalyzed reactions, such as Buchwald–Har-
twig, Heck, Sonogashira, and Suzuki–Miyaura reactions, are
increasingly important because of their advantages in forming dif-
ficult bonds, thus play a pivotal role in the synthesis and develop-
ment of drug molecules.5b However, even after several purification
steps, a high level of residual palladium species are still often found
in the final products which can be hazardous to human health,5c
because Pd can bind to thiol-containing amino acids, proteins
(casein, silk fibroin, and many enzymes), DNA or other macromol-
ecules (vitamin B6) and thereby may disturb a variety of cellular
processes.5d Therefore, analytical methods are urgently needed
for the sensitive and selective detection of Pd in a high throughput
fashion. The typically used analytical methods, such as atomic
absorption spectrometry, inductively coupled plasma atomic emis-
sion spectrometry, solid-phase microextraction high-performance
liquid chromatography, X-ray fluorescence, etc., all suffer from
the high cost of instruments and their requirement of highly
trained individuals.
Although colorimetric technique is frequently applied to the
determination of Pd2+ 4b,4f
the fluorescent method would be more
,
desirable because of the easy preparation, convenient operation,
and also the nondestructive, quick, and sensitive detection of emis-
sion signals. Holdt et al., designed a fluorescence off–on Pd2+ sensor
with a push pull dimercaptomaleonitrile moiety as the receptor
which can also regulate the photoinduced electron transfer in their
system.6 Based on the Pd-catalyzed Tsuji–Trost allylic oxidative
insertion reaction, Koide’s group developed a fluorescein system
as sensitive and selective fluorescent sensor for the residual Pd
analysis in reaction vessels and in real samples of drug, rock, and
soil.7 Besides these Pd-catalyzed reaction mechanisms,8 the rhoda-
mine spirolactam framework9 is also an ideal choice,10 among
which only Quah obtained the X-ray single crystal structure of
the Pd2+-sensor complex.10e
There have been several rhodamine hydrazone derivatives10g
developed as fluorescence-enhanced sensors for Pd2+ detection.
In our recent work, the rhodamine hydrazone derivatives
(Scheme 1) with allylidene receptor (RPd2 and RPd3)10c and tri-
dentate PNO receptor (RPd4)10f were adopted for specific detection
of Pd2+ over other PGEs ions and demonstrated their potential
application for Pd-control and Pd-analysis in the environment.
Actually, we found that the initial rhodamine hydrazone deriva-
tives (RPd1-a–c in Scheme 1) also display good coordination to
Pd2+ even without any additional modification. The cheap and
commercially available starting materials make these sensors easy
⇑
Corresponding authors. Tel./fax: +86 411 84986306.
E-mail addresses: fanjl@dlut.edu.cn (J. Fan), pengxj@dlut.edu.cn (X. Peng).
These authors contributed equally to this work.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.05.094

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H. Li et al. / Tetrahedron Letters 54 (2013) 4357–4361
EtHN
NHEt
EtHN
NHEt
O
O
EtHN
NHEt
O
l
C
b
a
N
N
N
NH2
O
O
R
O
O
Et
-
IM 1
c
d
EtHN
NHEt
O
,
,
,
=
RPd1-a, R = -H
RPd2
RPd3
RPd4
R
CN
=
R
R
RPd1-b, R = -CH3
C
N
N
N
O
O
=
RPd1-c, R = -CH2CH3
Ph2P
-
IM 2
Scheme 1. The structures and synthetic routes of rhodamine hydrazone Pd sensors. (a) and (b) for RPd1-a, RPd1-b, RPd1-c, RPd2, RPd4, (a), (c) and (d) for RPd3. (a),
Hydrazine, EtOH, refluxed, 88.5% for IM-1; (b), the aldehydes, EtOH, refluxed, 42.8% for RPd1-a, 62.3% for RPd1-b, 84.3% for RPd1-c, 85.2% for RPd2, 77.9% for RPd4; (c),
glyoxal, EtOH, refluxed, 66.2% for IM-2; (d), malononitrile, CH3CN, refluxed, 85.9% for RPd3.
to be obtained and may be developed as a common fluorescent re-
agent for Pd2+ sensing.
The rhodamine hydrazone derivatives RPd1-a, b, and c were
synthesized by a reported procedure12 in good yields (Scheme 1).
All intermediates and products were purified by recrystallization
that was much more convenient than column chromatography,
and characterized by 1H NMR, 13C NMR, and TOF-MS. For RPd1-c,
its X-ray crystal structure shows the characteristic spirolactam
framework (Fig. 1, left). K+, Ca2+, Mg2+, Zn2+, Cd2+, Ba2+, Cr3+, Pb2+
,
Cu2+, Hg2+, Ag+, Mn2+, Ni2+, Co2+, La3+, and NH4 ions were used to
+
evaluate the metal ion selectivity of RPd1-a, b, and c (10 lM) in
50% ethanolic water solution. Among these metal ions (2.0 equiv),
the sensors RPd1-a, b, and c all showed a large fluorescence
enhancement only with Pd2+ (Fig. 2), although Hg2+ induced a
small portion of fluorescence enhancement. The addition of Pd2+
to these sensors solution induced both colorimetric and fluoromet-
ric responses that can be easily detected by the naked eye (Fig. 2
inset, e.g., RPd1-c). In the Pd2+ titration experiments, there are also
new absorption peak centered at 540 nm and emission peak cen-
tered at 555 nm gradually generated on the absorption and emis-
sion spectra for all of the three sensors (Fig. 3 for RPd1-c,
Supplementary Fig. S3 for RPd1-a, Supplementary Fig. S4 for
Figure 2. Fluorescence intensity (at 555 nm) of RPd1-a (dark red), RPd1-b (red),
and RPd1-c (blue) samples with and without treatment of metal ions. Condition:
50% ethanolic aqueous solution, 10
l
M for each sensor, 20
lM for each metal ion,
kex = 505 nm. Inset photos: photos of RPd1-c (10
lM) in 50% ethanolic water
solution with and without 1.0 equiv of PdCl2, PtCl2, and RhCl3 under sunlight (left)
and UV light (right).
Figure 1. X-ray crystal structures of RPd1-c (left) and RPd1-c-Pd (right). Displacement ellipsoids are shown at the 30% probability level for RPd1-c and 60% probability level
for RPd1-c-Pd.11

H. Li et al. / Tetrahedron Letters 54 (2013) 4357–4361
4359
Figure 3. Absorption (a) and fluorescence (b) spectral changes of RPd1-c (10 l lM). kex = 505 nm.
M) in 50% ethanolic water solution after addition of Pd2+ (0–50
RPd1-b, respectively). The coordination constant Ka of RPd1-c-Pd
was 2.42 Â 106 MÀ2 L2 (Supplementary Fig. S5b), inferred from
the Hg2+ titration curves (Supplementary Fig. S5a).
in Supplementary Figures S8 and S9). However, when 1.0 equiv of
PdCl2 was added into RPd1-c in nonaqueous solution of MeOH/
DCM (1:1, v/v), the TOF-MS results showed the peak at m/z
619.1541 that corresponded to [PdRPd1-c(HCOOÀ)]+ cation (Sup-
plementary Fig. S10) demonstrating a different stoichiometry of
1:1 between Pd2+ and RPd1-c. The different stoichiometry results
were also observed by Job plots of RPd1-c in these two different
systems (Supplementary Fig. S11).
The X-ray single crystal structure of RPd1-c-Pd complex (incu-
bated in MeOH/DCM mixed solvents) also provided the coordina-
tion details. As can be seen clearly in Figure 1 right, two donor
atoms that are provided by the lactam and hydrazone ligands,
namely O2, N2, as well as two Cl atoms, describe a square–planar
coordination sphere of Pd2+ and Pd2+ well within the mean plane
that passes through the four donor atoms. The rhodamine part
was present in the form of a ring-opened amide conformation to
indicate the delocalized xanthene moiety, which shows the strong
absorption and emission. Therefore, RPd1-c would prefer 1:1 coor-
dination to Pd2+ in nonaqueous solution such as MeOH/DCM (1:1,
v/v). The Pd2+-coordination induced ring-opening reaction of
RPd1-c with different stoichiometries of 1:2 in EtOH/H2O and
1:1 in MeOH/DCM is shown in Scheme 2.
Additionally, PGE salts such as PdCl2, PtCl2, RhCl3, and RuCl3
were adopted to check whether RPd1-a, b, and c could selectively
detect the PGE ions. Supplementary Figure S6 shows the time
course (0–60 min) of fluorescence intensities of these sensors trea-
ted with and without Pd2+, Pt2+, Rh3+, and Ru3+, respectively. It can
be clearly observed that the selected PGE ions do not evidently en-
hance the fluorescence intensities, whereas Pd2+ leads to notable
fluorescence signal enhancements. The inset photos in Figure 2
also display the visual detection of RPd1-c to Pd2+ over Pt2+ and
Rh3+. As shown in Supplementary Figure S7, the fluorescence of
these sensors is pH independent at pH > 5. The resulting sigmoidal
curves give pKa of 3.70 for RPd1-a, 3.57 for RPd1-b, and 3.65 for
RPd1-c, respectively, demonstrating that they can work in a wide
physiological pH range.
In our previous work, we have figured out the mechanism that
Pd2+-coordination induced the ring-opening reaction of sensors
RPd2, 3, and 4 by Pd2+ titration experiment, TOF-MS result, and
X-ray single crystal structure analysis. The hydrazone binding site
has been considered as the key role in these sensors. In this work,
the first evidence of the binding mode came from TOF-MS result of
the complex RPd1-c and Pd2+ in 50% ethanolic water solution. The
peak at m/z 521.2543 that corresponds to [Pd(RPd1-c)2]2+ (Fig. 4)
was clearly observed to support the 1:2 stoichiometry for
Pd(RPd1-c)2 complexation. The same 1:2 stoichiometry was also
obtained for Pd(RPd1-a)2 and Pd(RPd1-b)2 (see the TOF-MS results
The partial fluorescence quenching8a,8c was also observed in
RPd1-c-Pd2+ complex which was revealed by density functional
theory (DFT) calculations (Fig. 5).13 HOMO of RPd1-c-Pd2+ is local-
ized on the Pd2+-ligand moiety and its energy level locates just be-
tween the frontier molecular orbitals of the xanthene fluorophore
(HOMO-5 and LUMO). Hence, the PeT (photo-induced electron
Figure 4. TOF-MS of RPd1-c (30
[Pd(RPd1-c)2]2+ cation.
lM) in the presence of 1.0 equiv PdCl2 in 50% ethanolic water solution. Insets: calculated (left) and observed (right) isotopic patterns for the

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H. Li et al. / Tetrahedron Letters 54 (2013) 4357–4361
EtHN
NHEt
O
EtHN
NHEt
O
N
EtHN
NHEt
O
N
Pd
O
N
Pd
O
N
N
N
N
N
Pd
O
O
l
C
l
C
NHEt
EtHN
O
e
M H D
O
E
t
O
H H
2O
/
M
C
/
Scheme 2. Pd2+-coordination induced ring-opening reaction of RPd1-c with different stoichiometries of 1:2 in EtOH/H2O and 1:1 in MeOH/DCM.
Figure 5. The calculated frontier molecular orbitals of RPd1-c-PdCl2 and their energy levels.
S.; Yoon, J. Chem. Soc. Rev. 2012, 41, 3210; (d) Qian, X.; Xiao, Y.; Xu, Y.; Guo, X.;
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to the fluorophore.
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In summary, we have developed a series of rhodamine spiro-leu-
co compounds as fluorescence-enhanced sensors for optical sensing
of Pd2+. The initial rhodamine hydrazone derivatives, RPd1-a, RPd1-
b, and RPd1-c, display a good coordination to Pd2+ inducing the spi-
rolactam-opening reaction with a significant fluorescence enhance-
ment and color generation. The different stoichiometries (based on
TOF-MS and X-ray single crystal structure) of RPd1-c/Pd2+ were ob-
tained in EtOH/H2O and MeOH/DCM, demonstrating the different
coordination patternsinaqueous/non-aqueoussolutions. Moreover,
these sensors can be easily synthesized from the cheap and commer-
cially available starting materials by convenient purification process
and in good yields, which all make them easy to be developed as
common fluorescent reagents for Pd2+ sensing.
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Acknowledgments
This work was financially supported by the NSF of China
(21136002, 20923006 and 21076032), National Basic Research
Program of China (2009CB724706 and 2013CB733702), and Na-
tional High Technology Research and Development Program of Chi-
na (863 Program, 2011AA02A105).
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Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.
05.094.
References and notes
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11. CCDC 921199 & 921200 contain the supplementary crystallographic data for
this Letter. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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13. The geometry optimizations were performed by using DFT with B3LYP
functional and 6–31 g⁄ basis set for H, C, N, O, and P atoms and standard
LanL2DZ basis set for Pd.