Rational design of a NIR-emitting Pd(ii) sensor via oxidative cyclization to form a benzoxazole ring

Article abstract of DOI:10.1039/c2cc30240c

By using the substituent effect to tune the palladium(ii)-involved reactivity, a new probe is found to respond quantitatively to Pd(ii). Unexpectedly, the probe gave an emission band in the desirable near-infrared (NIR) region (780 nm), thus providing the

Full text of DOI:10.1039/c2cc30240c

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Rational design of a NIR-emitting Pd(II) sensor via oxidative cyclization
to form a benzoxazole ringw
Weihua Chen, Brian D. Wright and Yi Pang*
Received 11th January 2012, Accepted 22nd February 2012
DOI: 10.1039/c2cc30240c
By using the substituent effect to tune the palladium(II)-involved
reactivity, a new probe is found to respond quantitatively to
Pd(II). Unexpectedly, the probe gave an emission band in the
desirable near-infrared (NIR) region (780 nm), thus providing
the first NIR sensor for palladium detection.
a challenge, due to the specific requirement for the palladium-
involved chemistry and the limited choice of the resulting NIR
dye structures.
As a unique fluorophore 2-(20-hydroxyphenyl)-benzoxazole
(HBO) derivatives 2 exhibit unusually large Stokes shift
(ca. 150–200 nm), attributing to their intrinsic ability to undergo
the excited state intramolecular proton transfer (ESIPT).12 Recent
observation of NIR emission13 from ESIPT raises the possibility
that a properly designed structure could simultaneously achieve
both large Stokes shift and NIR emission. Herein we demonstrate
that such a NIR-emitting fluorophore could be generated by
palladium(II)-catalyzed oxidative cyclization of 1. The study stems
from our recent finding that HBO 2 can be effectively synthesized
by palladium(II)-catalyzed oxidative cyclization of 1 (Y = H)
at B80 1C,14 whose optimization makes it suitable for palladium
sensing at ambient temperature. The sensor design incorporates
palladium-catalyzed synthesis activity into sensor detection
(Scheme 1), offering an attractive solution to achieve the metal
detection with both NIR emission and large Stokes shift.
The conversion of unsubstituted 1 (Y = H) to 2 is known to
occur slowly at room temperature (e.g. 55% conversion
requires about 12 h).14 In order to raise the reaction rate to
a practically useful level for sensor application, we decided to
investigate the substitution effect on the reaction rate of 1.
Thus imine derivatives 1 were synthesized and their conversion
to 2 was examined at ambient temperature. The Hammett
plot15 showed a good linear correlation (Fig. 1). The result
Increasing interest exists in developing a simple and effective
methodology for fluorescent detection of palladium species, as
the palladium contents need to be monitored in the drug
intermediates which are increasingly synthesized by using
palladium catalysts. Wide use of palladium in automobile
catalytic converters has also raised the palladium emissions
in our environments which include water resources, soils, dusts
and biological plants.1 Palladium levels could also pose some
risks to human health, as very low doses of palladium are
known to cause allergic reactions in susceptible individuals.2
Because of the low palladium concentration in the environmental
samples (e.g. B20 ng Lꢀ1 in fresh water), analytical techniques
with a high sensitivity and selectivity are desirable, which can
directly determine the Pd levels without the tedious sample
preconcentration and/or separation of the analyte from the matrix.
In this regard, fluorescent palladium sensors offer an attractive
option, due to their simplicity and extremely low detection limit.
Some progress has been made in the development of fluorescent
indicators for palladium,3–7 with recent examples to illustrate
palladium in biological imaging8,9 and intercellular chemical
reaction.10 Nearly all the known systems, however, recognize
palladium by the changes in fluorescence intensity. In addition,
most of the reported fluorescent indicators for palladium are
based on the fluorescein9 and rhodamine fluorophores,11 which
possess small Stokes shifts and give emission in the visible region.
In order to overcome the autofluorescence from biological
samples, it is highly desirable for a fluorophore to exhibit
large Stokes shifts and give emission in the near infrared (NIR)
region (700–900 nm). Development of a palladium sensor with
large Stokes shift and near infrared emission, however, remains
Department of Chemistry & Maurice Morton Institute of Polymer
Science, The University of Akron, Akron, OH 44325, USA.
E-mail: yp5@uakron.edu; Tel: +1 330-972-8263
w Electronic supplementary information (ESI) available: Synthesis
and characterization, and absorption spectra of compounds 5 and 6.
CCDC 868982. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c2cc30240c
Scheme 1 Synthesis of HBO derivatives via palladium(II) catalyzed
cyclization.
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3824 Chem. Commun., 2012, 48, 3824–3826
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Fig. 1 Hammett plot for palladium (II)-catalyzed reaction of 1 with
different substituent Y. The plot was constructed by carrying out the
reaction in a 5 mL vial, using CD3CN as solvent. One equiv. of PdCl2
was used and toluene or 1,4-dioxane was added as internal standard to
determine conversion of the reaction at 25 1C in 1 hour.
Fig. 2 (a) Fluorescence response of 5 (2.5 mM) upon addition of
0–1.0 equiv. of PdCl2 in acetonitrile with 1%(w/v) dimethylglyoxime at
25 1C (excitation at 360 nm). The spectra were acquired after mixing for
20 minutes. Inset: time-dependent intensity change at 780 nm. (b) Color
change and (c) fluorescence images of 5 before and after addition of
1.0 equiv. of PdCl2 in acetonitrile with 1% (w/v) dimethylglyoxime, after
20 minutes. (d) Dependence of fluorescence intensity at 780 nm on the equiv.
of Pd(PPh3)2Cl2, at 25 1C in acetonitrile with 5%(w/v) dimethyglyoxime.
Scheme 2 Sensing mechanism of 5 toward Pd(II). The right picture
shows the crystal structure of 6.
indicates that the reaction rate can be increased significantly
when the substituent ‘‘Y’’ is an electron-withdrawing group.
The experimental finding could be rationalized by considering
the rate-determining step, i.e. Pd(II)-assisted intramolecular
cyclization (3 - 4). It is noteworthy that the conversion from
3 to 4 (without Pd binding) is a 5-endo-trig cyclization which is
disfavoured by Baldwin’s rule. The substituent Y influences
the electron density on the imine CQN group via the inductive
effect, thereby raising the imine’s electrophilic property to
facilitate the rate-determining cyclization step.
When 1.0 equiv. of sensor 5 was used, the fluorescence gradually
increased and saturated within 45 minutes (Fig. 2a, inset).
A comparison of the fluorescence intensity from air-saturated
(no degassing) solution and degassed solution at 25 1C shows
no difference (Fig. S4, ESIw), indicating that oxygen has no
effect on the reaction 5 - 6 and on the fluorescence of 6 in
acetonitrile at room temperature. Because the fluorescence of
sensor 5 itself is negligible in comparison with that of 6, more
than one equiv. of 5 can be used for a faster measurement. For
instance, the fluorescence saturation could be attained within
5 minutes when 5 equiv. of 5 were used. Fig. 2d shows the
response of sensor 5 in the presence of Pd(II) in a 1 : 1
stoichiometry, illustrating the sensor’s application for quantitative
determination of Pd(II) species. The formation of benzoxazole 6
was confirmed by synthesizing it separately from an equimolar
mixture of 5 and PdCl2 in acetonitrile. Similar responses
were observed from Pd(OAc)2, Pd(dppf)2Cl2 and Pd(PPh3)2Cl2,
proving the general use of sensing Pd(II).
Guided by the observed substitution effect, we synthesized
the HBO derivative 5 (Scheme 2), which included a strong
electron-withdrawing group –CHQC(CN)2. The solution of 5
in 5% water–acetonitrile was yellow, exhibiting a broad
structureless absorption band (lmax E 395 nm, Fig. S2, ESIw).
Addition of Pd(II) species (e.g. PdCl2 or Pd(PPh)2Cl2) produced a
colorless solution (lmax = 355 nm), as a consequence of forming
the benzoxazole ring in 6 (Fig. S3, ESIw). The absorption
spectrum of 6 showed three relatively sharp absorption peaks
(lmax E 305, 331 and 360 nm), due to its rather rigid molecular
structure. Interestingly, addition of Pd(II) to nonfluorescent 5
gave a highly fluorescent 6, showing a strong green fluorescence
(lem = 522 nm) and a near infrared emission band (lem = 780 nm)
(Fig. 2). In other words, the new palladium(II) sensor 6
exhibited two well separated emission bands in visible and
NIR regions, with unusually large Stokes shift (Dl1 = 162 nm;
Dl2 = 420 nm).
The fluorescence response of sensor 5 toward various other
metal ions (Mn2+, Cr2+, Fe2+, Fe3+, Cr2+, Pt2+, Ag+,
Co2+, Ni2+, Na+, K+, Mg2+, Ca2+, Zn2+, Cd2+, Hg2+
,
Pb2+, Rh3+, Rh+, Cu2+) was also examined. However, metal
ions other than Pd2+ showed little spectral or color changes
(Fig. 3). A similar response was observed when Pd2+ was
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Chem. Commun., 2012, 48, 3824–3826 3825

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In summary, a unique fluorogenic probe has been developed
for specific recognition of Pd2+ species, by tuning the chemical
reactivity of Pd2+-involved oxidative cyclization. The sensing
mechanism is based on the formation of HBO structure to give
strong visible emission (lfl = 522 nm). In sharp contrast to the
existing palladium sensor, the new HBO derivative gives an
additional emission band in the NIR region (lfl = 780 nm)
with large Stokes shift (Dl E 420 nm). The study thus
provides the first example to successfully couple the palladium
reactivity to enable the ESIPT mechanism (from 6 to 7),
which generates the longest wavelength emission observed so
far from ESIPT. The developed new NIR probe could be a
useful tool for the in vivo study of palladium-related biology,
as the NIR signals would minimize the interferences from
autofluorescence in biological samples, thereby permitting
deep penetration of optical signal under skin. The ability of
using ESIPT to generate specific electronic interaction that is
only available in the excited state, as shown in 7, would be a
useful guide in further tuning NIR emission wavelength for
improved photophysical characteristics. Two well separated
emissions, in addition to potential metal binding of the
resulting HBO, also raise the possibility for simultaneous
detection of multiple ions.
Fig. 3 Fluorescence intensity (at 780 nm) of 5 (2.5 mM) in acetonitrile
with 1% (w/v) dimethylglyoxime at 25 1C, taken 1 hour after addition
of 1.0 equiv. of metal ions.
This work was supported by The University of Akron
through Coleman Endowment. W. Chen acknowledges the
Dr Franklin G. Strain Scholarship from the department of
chemistry.
Notes and references
Fig. 4 A fluorescence intensity profile of 5 at 780 nm upon addition
of Pd2+ (0.1–0.35 ppm).
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detection limit of sensor 5 to be 0.1 ppm.
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