Fluorogenic and chromogenic detection of palladium species through a catalytic conversion of a rhodamine b derivative

Article abstract of DOI:10.1021/ol100905g

(Figure presented) A simple yet efficient detection method for palladium species is developed based on a molecular sensing system that undergoes a palladium-catalyzed oxidative addition. A rhodamine B derivative thus developed undergoes the catalytic proc

Full text of DOI:10.1021/ol100905g

ORGANIC
LETTERS
2010
Vol. 12, No. 12
2790-2793
Fluorogenic and Chromogenic Detection
of Palladium Species through a Catalytic
Conversion of a Rhodamine B Derivative
Mi Eun Jun and Kyo Han Ahn*
Department of Chemistry and Center for Electro-Photo BehaViors in AdVanced Molecular
Systems, POSTECH, San 31, Hyoja-dong, Pohang, 790-784 Republic of Korea
ahn@postech.ac.kr
Received April 20, 2010
ABSTRACT
A simple yet efficient detection method for palladium species is developed based on a molecular sensing system that undergoes a palladium-
catalyzed oxidative addition. A rhodamine B derivative thus developed undergoes the catalytic process triggered by palladium insertion and
gives both turn-on fluorescence and color changes. A usefulness of the sensing system is demonstrated by determining the residual palladium
contents in a purified sample prepared through a palladium-catalyzed reaction.
Detection of palladium species with a fluorescence sensing
system is drawing current research interest as an easy and
sensitive method for determining the palladium contents in
the drug intermediates synthesized by palladium catalysis
or in mining ores, etc. Detection of palladium contents in
those samples is usually carried out using analytical tools
such as atomic absorption/emission spectrophotometry, ion-
coupled plasma emission-mass spectrometry, and X-ray
fluorescence spectroscopy.1 These conventional methods,
however, require large and expensive instruments as well
as sophisticated experimental procedures such as complex
sample pretreatments and precautions of cross-contamination
from the prior analysis. In contrast, the fluorogenic detection
method can be performed with a hand-held fluorimeter
through relatively simple analysis protocols. Moreover, the
chromogenic detection with the naked eye does not require
any instruments, albeit less sensitive than the fluorescence
method. Many fluorescent sensing systems for metal ions
and small molecular anions have been developed, but still
highly selective and “turn-on” type systems are desired. To
achieve high selectivity and sensitivity, the reaction-based
fluorescent sensing approach is attractive.2
Recently, Koide and co-workers reported a turn-on fluo-
rescent sensing system for palladium based on the palladium-
catalyzed Tsuji-Trost allylic addition reaction:3 an allylated
fluorescein, which is nonfluorescent, undergoes the catalytic
deallylation reaction with Pd(0) generated in situ from the
Pd(II) species to regenerate the fluorecein, a highly fluores-
(1) (a) Van Meel, K.; Smekens, A.; Behets, M.; Kazandjian, P.; Van
Grieken, R. Anal. Chem. 2007, 79, 6383. (b) Locatelli, C.; Melucci, D.;
Torsi, G. Anal. Bioanal. Chem. 2005, 382, 1567. (c) Dimitrova, B.;
Benkhedda, K.; Ivanova, E.; Adams, F. J. Anal. At. Spectrom. 2004, 19,
1394.
(2) (a) Cho, D. G.; Sessler, J. L. Chem. Soc. ReV. 2009, 38, 1647. (b)
Kim, H. N.; Lee, M. H.; Kim, H. J.; Kim, J. S.; Yoon, J. Chem. Soc. ReV.
2008, 37, 1465.
10.1021/ol100905g  2010 American Chemical Society
Published on Web 05/14/2010

cent compound. A typical palladium species, PdCl2, is thus
detected with high selectivity and sensitivity in the presence
of triphenylphosphine, tris(2-thiopenyl)phosphine (TFP), or
TFP-NaBH4. They have shown that the sensing system and
subsequent more elaborate ones4 are promising for the
detection of palladium as well as platinum species in several
samples.
the amide group at room temperature and thus causes the
peak splitting.
Scheme 1. Spirolactam Ring-Opening Process Triggered by
Pd(0)-Catalyzed Insertion, Which Gives a Turn-on Fluorescence
Change
We have developed some reaction-based fluorescent sens-
ing systems for anions and metal cations,5 including rhodamine
dye-based ones.5b,e Spirolactam derivatives of rhodamine
dyes are useful sensing platforms because the spirolactam
ring-opening process leads to a turn-on fluorescence
change.2b An additional advantage of such a rhodamine-based
sensing system is that the ring-opening process is also
accompanied by a vivid color change from colorless to pink,
thus enabling detection simply with the naked eye. Herein,
we wish to report an iodophenyllactam derivative of rhodamine
B as an efficient fluorogenic and chromogenic sensing system
for palladium species. Our rationale in the probe design is
depicted in Scheme 1: A palladium intermediate I once
generated by the oxidative insertion of Pd(0)6 species to
probe 1 may undergo spirolactam ring opening as the
carboxamide oxygen coordinates to the corresponding Pd(II)
intermediate. A subsequent reductive elimination process will
lead to benzoxazole 2, which is expected to be highly
fluorescent because of a conjugated nature of the 6-amino-
xanthen-3-ylidene-ammonium moiety. An apparent color
change is also expected in addition to the turn-on fluores-
cence change. During our study, Peng and co-workers
reported a rhodamine-based probe that senses palladium
through metal coordination rather than catalytic conversion.
Such a coordination-based sensing system is sensitive to the
metal ligands and consequently to the solvent used, an
obvious drawback.7
A solution of probe 1 in acetonitrile is colorless and
nonfluorescent. To detect the Pd(II) species such as PdCl2
according to the mechanism depicted in Scheme 1, a reducing
agent is required to convert it to the Pd(0) species. We have
found that [(t-Bu)3PH]BF4 converts PdCl2 into the Pd(0)
species, which readily undergoes the oxidative insertion to
the iodophenyl group at 85 °C.9 When a solution of probe 1
in acetonitrile (10 µM) was treated with PdCl2 (0.1 equiv to
the probe) and [(t-Bu)3PH]BF4 (2-4 equiv to the PdCl2),10
the colorless solution became pink (absorption λmax ) 520,
560 nm), and its fluorescence was turned on, from dark to
bright orange (emission λmax ) 580 nm; excitation wave-
length ) 540 nm) (Figure 1a). This catalytic turn-on process
under the dilute conditions required an initiation step for ∼25
min and then proceeded readily within 1 h (Figure 2b). The
results indicate that the palladium-catalyzed insertion reaction
indeed triggers the spirolactam ring opening, as we intended
in the probe design. Efforts to isolate the product 2 were
Probe 1 was synthesized from rhodamine B in 87% yield
(POCl3, 1,2-dichloroethane, reflux for 4 h; 2-iodoaniline,
Et3N, acetonitrile, 25 °C for 5 h).8 Interestingly, the 13C NMR
spectrum of probe 1 showed 24 separate peaks for the 24
aromatic carbons, owing to atropisomerism: the iodophenyl
group seems to experience hindered rotation with respect to
(3) (a) Song, F.; Garner, A. L.; Koide, K. J. Am. Chem. Soc. 2007, 129,
12354. (b) Garner, A. L.; Song, F.; Koide, K. J. Am. Chem. Soc. 2009,
131, 5163. For other reports that do not rely on the reaction-based sensing
approach: (c) Schwarze, T.; Mu¨ller, H.; Dosche, C.; Klamroth, T.; Mickler,
W.; Kelling, A.; Lo¨hmannsro¨ben, H. G.; Saalfrank, P.; Holdt, H. J. Angew.
Chem., Int. Ed. 2007, 46, 1671. (d) Houk, R. J. T.; Wallace, K. J.; Hewage,
H. S.; Anslyn, E. V. Tetrahedron 2008, 64, 8271. (e) Duan, L.; Xu, Y.;
Qian, X. Chem. Commun. 2008, 6339.
(4) (a) Garner, A. L.; Koide, K. J. Am. Chem. Soc. 2008, 130, 16472.
(b) Garner, A. L.; Koide, K. Chem. Commun. 2009, 83. (c) Garner, A. L.;
Koide, K. Chem. Commun. 2009, 86.
(5) (a) Ryu, D.; Park, E.; Kim, D. S.; Yan, S.; Lee, J. Y.; Chang, B. Y.;
Ahn, K. H. J. Am. Chem. Soc. 2008, 130, 2394. (b) Chatterjee, A.; Santra,
M.; Won, N. Y.; Kim, S. J.; Kim, J. K.; Kim, S. B.; Ahn, K. H. J. Am.
Chem. Soc. 2009, 131, 2040. (c) Kim, D. S.; Chung, Y. M.; Jun, M. E.;
Ahn, K. H. J. Org. Chem. 2009, 74, 4849. (d) Santra, M.; Ryu, D.;
Chatterjee, A.; Ko, S. K.; Shin, I.; Ahn, K. H. Chem. Commun. 2009, 2115.
(e) Egorova, O. A.; Seo, H.; Chatterjee, A.; Ahn, K. H. Org. Lett. 2010,
12, 401.
Figure 1. Photos that show (a) color and (b) fluorescence changes
for a solution containing probe 1 (10 µM), PdCl2 (1.0 µM), and
[(t-Bu)3PH]BF4 (4.0 µM) in acetonitrile, taken after 30 min at 85
°C. (c) Fluorescence spectral changes of probe 1 upon treatment
with PdCl2 (0.1 µM) and [(t-Bu)3PH]BF4 (0.4 µM) in acetonitrile,
measured after 1 h at 85 °C (excitation at 540 nm).
(6) Beller, M.; Zapf, A. Handbook of Organopalladium Chemistry for
Organic Synthesis; Negish, E., Ed.; Wiley: New York, USA, 2002; Vol. 1,
p 1209.
(7) Li, H.; Fan, J.; Du, J.; Guo, K.; Sun, S.; Liu, X.; Peng, X. Chem.
Commun. 2010, 46, 1079.
(8) See the Supporting Information.
Org. Lett., Vol. 12, No. 12, 2010
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not successful because of its instability during silica gel
chromatography; however, its formation was supported by
in situ NMR analysis for the reaction mixture.8
selective detection of palladium in the presence of various
other metal species as well as Pt(II). Furthermore, we can
detect palladium species simply with the naked eye.
The present sensing protocol also applies to other pal-
ladium species such as Pd(OAc)2 and Pd2dba3, which
behaved similarly to PdCl2 under the detection conditions.8
Sulfur-containing compounds may interfere with the
palladium sensing.3a,b We examined the sensing of PdCl2
described above in the presence of N-acetyl-L-cysteine (5
equiv to PdCl2), but there was no change in the fluorescence
enhancement.8
Figure 2. (a) Time-dependent fluorescence spectral changes of
probe 1 (10 µM) upon treatment with PdCl2 (1.0 µM) and
[(t-Bu)3PH]BF4 (4.0 µM) in acetonitrile at 85 °C (excitation at 540
nm). (b) A plot of the fluorescence intensity change versus the
reaction time.
Next, we investigated the sensing behavior of probe 1
toward various other metal chlorides under the established
conditions: the catalytic turn-on process occurs only in the
case of the palladium species, and other metal species such
as Pt(II), Fe(II), Fe(III), Ni(II), Mn(II), Cu(II), Mg(II), Cr(II),
and Co(II) do not cause any noticeable fluorescence changes
(Figure 3). The palladium sensing is not interrupted in the
presence of the other metal species including Zn(II) and
Al(III) or acidic compounds such as acetic acid (5 equiv to
PdCl2).8 Notably, the present system does not respond to
Pt(II), which coexists with Pd(II) speices in ores and also
competes with Pd(II) in the sensing studies.4a
Figure 4. Determination of residual palladium contents in the
compound 3 that is synthesized by a palladium-catalyzed reaction
and purified by column chromatography. Photos that show both
(a) color and (b) fluorescence changes for the purified 3, after
treatment with probe 1 (50 µM) and [(t-Bu)3PH]BF4 (50 µM) in
acetonitrile at 85 °C for 1 h. (c) Fluorescence spectra taken for the
purified 3 (in red) and for the reference samples containing a known
amount of the palladium catalyst [(Ph3P)4Pd], after treatment with
probe 1 under the same conditions (excitation at 540 nm): Arabic
numbers on the spectra are in parts per billion units and indicate
the amount of the palladium catalyst in each reference sample; the
“1st”, “2nd”, and “3rd” indicate the samples of product 3 that are
purified by column chromatography on silica gel once, twice, and
three times, respectively. Inset: an expanded plot for the region of
1-20 ppb of the catalyst.
Figure 3. Fluorescence enhancement data of probe 1 (10 µM)
toward various metal species (1.0 µM, as the chloride salt) in the
presence of [(t-Bu)3PH]BF4 (4.0 µM) in acetonitrile, measured after
1 h at 85 °C (excitation at 540 nm).
The excellent selectivity observed should be originated
from the metal-specific catalytic reaction. The present Pd(0)-
catalyzed oxidative addition process does not occur with
Pt(II), whereas the Tsuji-Trost allylic addition (Koide’s
system) seems to occur with both the metal catalysts.3
Therefore, the present sensing protocol can be used for the
To demonstrate a potential usefulness of probe 1 for the
detection of residual palladium contents in the chemical
(9) PPh3 also caused the insertion but much less efficiently.
(10) 2-4 equiv of [(t-Bu)3PH]BF4 can be used.
2792
Org. Lett., Vol. 12, No. 12, 2010

products produced by palladium-catalyzed reactions, we
carried out a known palladium-catalyzed reaction and
analyzed the residual palladium content in the product
depending on the number of purifications by column chro-
matographyonsilicagel(Figure4).Thus,theSuzuki-Miyaura
coupling reaction was carried out between 2-bromoanisole
(300 mg, 1.6 mmol) and (3-ethyloxycarbonyl)benzene bo-
ronic acid (342 mg, 1.8 mmol) in the presence of 2 mol %
of [(PPh3)4Pd] (37 mg, 0.03 mmol). The coupled product,
(2′-methoxy)biphenyl-3-carboxylic acid ethyl ester, was
isolated by standard extractive workup with ethylacetate,
dried over anhydrous magnesium sulfate, and purified by
column chromatography on silica gel (30 g; eluent, EtOAc/
n-hexane ) 1/4, by volume) to give 3 in 92% yield. This
“1st-purified” product was analyzed by fluorimetry using
probe 1 (50 µM) under the established conditions to
determine the residual palladium content in it.
A solution of the first-purified sample showed bright pink
(Figure 4a) as well as orange fluorescence (Figure 4b),
indicating that a significant amount of palladium remains in
the sample. In comparison with the fluorescence spectra
obtained for the samples of known amounts of the palladium
catalyst, we were able to determine the palladium content
in the first-purified sample (3.84 mg) to be 10.2 ppm.11 By
purifying the first-purified sample again (second purification)
through column chromatogrphy (silica gel, 30 g), the
palladium content became 960 ppb, and after the third
purification (silica gel, 30 g) the content became 110 ppb.8
These results clearly demonstrate that probe 1 is potentially
useful as an easy and sensitive method for determing the
residual palladium content in chemical products produced
by various palladium-catalyzed reactions. The allowed
content of heavy metals in drug chemicals is below 10 ppm,12
which indicates that we can readily monitor the residual
palladium content in drug intermediates using the present
sensing system. The palladium content in persons with
amalgam fillings and metallic dental appliances is 10.6 (
7.4 ppm from samples of morning saliva.13
In summary, we have developed a novel fluorogenic and
chromogenic sensing system for palladium species based on
the metal-catalyzed oxidative insertion reaction. The io-
dophenylspirolactam derivative of rhodamine B thus under-
goes the palladium-catalyzed insertion reaction and triggers
spirolactam ring opening, which accompanies both turn-on
fluorescence and color changes. The catalytic ring-opening
process is specific toward palladium species, and thus the
sensing system can be used for the detection of palladium
among various other metal species.
Acknowledgment. This work was supported by grants
from the EPB Center (R11-2008-052-01001). We thank Won
Sang Yoo (Korean Minjok Leadership Academy) for his
participation in this work through a summer internship
program.
(11) The weight of the solvent used and the weight percentage of
palladium in the catalyst are accounted for in the calculation of the palladium
content. See the Supporting Information for details.
(12) Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T. Org. Biomol.
Chem. 2006, 4, 2337.
Supporting Information Available: Synthesis and char-
acterization of probe 1 and the fluorescence data mentioned.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(13) International Programme on Chemical Safety. Palladium; Envi-
ronmental Health Criteria Series 226; World Health Organization: Geneva,
2002.
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