A fluorescence-enhanced chemodosimeter for Fe3+ based on hydrolysis of bis(coumarinyl) Schiff base

Article abstract of DOI:10.1002/ejoc.200800077

Bis(coumarinyl) Schiff base 1 was designed and synthesized as a fluorescence turn-on chemodosimeter for Fe³⁺. The chemodosimeter was readily synthesized in four steps from 2,4-dihydroxybenzaldehyde. The addition of Fe³⁺ to chemodosimeter 1 induced about a 140-fold enhancement in fluorescence. Furthermore, chemodosimeter 1 was also highly selective to Fe ³⁺ over other metal ions, and most of the related metals ions exhibited negligible detection interference. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800077

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200800077
A Fluorescence-Enhanced Chemodosimeter for Fe3+ Based on Hydrolysis of
Bis(coumarinyl) Schiff Base
Weiying Lin,*[a] Lin Yuan,[a] Jianbo Feng,[a] and Xiaowei Cao[a]
Keywords: Probes / Iron / Fluorescence / Schiff bases
Bis(coumarinyl) Schiff base 1 was designed and synthesized
as a fluorescence turn-on chemodosimeter for Fe3+. The
chemodosimeter was readily synthesized in four steps from
2,4-dihydroxybenzaldehyde. The addition of Fe3+ to chemo-
dosimeter 1 induced about a 140-fold enhancement in
highly selective to Fe3+ over other metal ions, and most of
the related metals ions exhibited negligible detection inter-
ference.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
fluorescence. Furthermore, chemodosimeter
1 was also
acidic water molecules.[11] Thus, we reasoned that Fe3+ may
also hydrolyze Schiff bases in an analogous way. On the
basis of this consideration, in this work, bis(coumarinyl)
Schiff base 1 was designed and synthesized as the first ex-
ample of a fluorescence turn-on Fe3+ chemodosimeter. Flu-
orescent chemodosimeters are molecular devices that utilize
abiotic receptors to achieve analyte recognition with
irreversible transduction of a fluorescent signal.[12] The
major difference between a chemodosimeter and a sensor is
that the signaling response of the former is irreversible,
whereas that of the latter is reversible. Coumarin dyes are
an important class of fluorescent compounds widely used
in probes because of their excellent photophysical proper-
ties.[13] It was envisioned that bis(coumarinyl) Schiff base 1
is “off” in fluorescence due to a photoinduced charge-
transfer (PCT) process (from the electron-donating C=N
moiety to the coumarin ring), which quenches the excited-
state emission of the coumarin fluorophore.[1–3] However,
upon addition of Fe3+, bis(coumarinyl) Schiff base 1 is hy-
drolyzed to release highly fluorescent coumarin dye 4
(Scheme 1).
Introduction
Fluorescent probes for metal ions have received great at-
tention in the last few decades due to their useful applica-
tions in environment, biology and chemistry.[1–3] Iron is an
essential trace element that plays significant roles in chemi-
cal and biological processes.[4,5] Therefore, the detection of
trace amounts of Fe3+ ions is critical. Indeed, enormous
efforts have been devoted to the development of Fe3+
probes. However, most of them undergo a fluorescence
quenching response because of the paramagnetic nature of
Fe3+ [6]
In most practical applications of fluorescent probes,
.
fluorescence enhancement when interacting with analytes is
much more desirable than fluorescence quenching. Never-
theless, the fluorescence quenching character of Fe3+ pres-
ents a challenge to develop selective, as well as sensitive,
fluorescence turn-on Fe3+ probes. Recently, very limited
cases of fluorescence-enhanced Fe3+ sensors have been re-
ported,[7] most of which employed the well-studied equilib-
rium between the fluorescence “off” spirocyclic form and
the fluorescence “on” open-ring form of rhodamine deriva-
tives.[7b–7d]
Herein, we described a fluorescence turn-on chemodosi-
meter for Fe3+ based on metal-promoted hydrolysis of bis-
(coumarinyl) Schiff base. Chemodosimeter 1 was readily
synthesized in a few steps. The addition of Fe3+ to chemo-
dosimeter 1 induced about a 140-fold enhancement in fluo-
rescence intensity. Moreover, 1 was also highly selective to
Fe3+ over other metal ions, and most of the related metals
ions exhibited negligible detection interference. As most
transition-metal ions possess intrinsic fluorescence quench-
ing properties, it is very challenging to construct their fluo-
rescence-enhanced sensors.[14] However, alternatively, the
design approach for this chemodosimeter should open a
new avenue for the development of fluorescence turn-on
chemodosimeters for other transition-metals ions by em-
ploying a particular metal-promoted reaction.
Schiff bases are important intermediates involved in
many enzymatic transformations. The mechanisms of hy-
drolysis of Schiff bases by acids and amines have been inves-
tigated in great detail.[8] In addition, it is known that Schiff
bases are also subject to metal-promoted hydrolysis.[9] On
the other hand, Fe3+ is a strong Lewis acid with a pKa of
2.83.[10] It was reported that Fe3+ could facilitate imid-
azolidine and phosphate ester hydrolysis by coordinated
[a] College of Chemistry and Chemical Engineering, Hunan Uni-
versity,
Changsha, Hunan 410082, P. R. China
Fax: +86-731-8821464
E-mail: weiyinglin@hnu.cn
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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W. Lin, L. Yuan, J. Feng, X. Cao
SHORT COMMUNICATION
hancement in the fluorescence intensity was observed even
after 5 min. The fluorescence intensity reached a maximum
after about 50 min. Thus, an assay time of 50 min was cho-
sen to further explore the sensitivity and selectivity of
chemodosimeter 1 toward Fe3+. Furthermore, after treat-
ment of chemodosimeter 1 with Fe3+ for 50 min, the ad-
dition of EDTA, an Fe3+ chelating agent, did not reduce the
fluorescence intensity, which demonstrates the irreversible
nature of this hydrolysis process promoted by Fe3+ and
which is characteristic of a chemodosimeter.[12] The forma-
tion of coumarin aldehyde 4 as the hydrolysis product was
confirmed by a comparative study with authentic com-
pound 4 through excitation and emission spectra (Fig-
ure S1, Supporting Information). In addition, hydrolysis
product 4 was also separated and characterized by TLC, 1H
NMR spectroscopy and MS analysis. In addition, 60 µ of
Fe3+ ions in CH3OH/H2O solution (98:2) in the absence of
chemodosimeter 1 did not display any fluorescence, which
Scheme 1. Design concept of fluorescence “on” Fe3+ chemodosi-
meter.
Results and Discussion
A convenient synthetic route to chemodosimeter 1 was further confirms that the fluorescence enhancement ob-
developed as shown in Scheme 2. Condensation of 2,4-di- served is indeed from hydrolysis product 4.
hydroxybenzaldehyde with propanoic anhydride in re-
fluxing propionic anhydride gave compound 2 in modest
yield,[15] which was then butylated with nBuBr to afford
coumarin 3 in 77% yield. Reaction of 3 with an excess
amount of NBS provided the dibromide intermediate,
which was further hydrolyzed with NaOAc in acetic acid to
afford the key intermediate, coumarin aldehyde 4 in 84%
yield.[16] Finally, chemodosimeter 1 was obtained by con-
densation of 4 (2 equiv.) with ethylenediamine in anhydrous
acetonitrile (yield: 64%). The structures of the inter-
mediates and final product were confirmed by NMR spec-
troscopy, MS (ESI) and elementary analysis.
Figure 1. Reaction–time profile of chemodosimeter 1 (5 µ) in the
absence (᭹) and presence (᭡) of Fe3+ (12 equiv.) in CH3OH /H2O
solution (98:2). The fluorescence intensity at λem = 392 nm was
plotted versus time.
Titration of 1 (5 µ) with Fe3+ ions was performed in
CH3OH/H2O solution (98:2). Figure S2 (Supporting Infor-
mation) shows the excitation spectra of 1 in the absence or
presence of Fe3+ (12 equiv.). Free 1 exhibits an excitation
peak with a maximum at 337 nm, which then blueshifts to
326 nm upon addition of Fe3+. It is noteworthy that the
excitation wavelength maximum of 4 is 326 nm (Figure S1,
Supporting Information), which is consistent with the for-
mation of hydrolysis product 4 upon treatment of 1 with
Fe3+. As designed, in the absence of metal ions, only a weak
broad emission band with maximum around 402 nm was
observed for free 1 (Figure S3, Supporting Information).
The fluorescence quantum yield of 1 was measured as 0.004
Scheme 2. Synthetic route to 1. Reagents and conditions: (a)
CH3CH2COONa, (CH3CH2CO)2O, triethylamine, reflux, 6 h,
48.7%; (b) nBuBr, acetone, K2CO3, reflux, 5 h, 77.3%; (c) NBS,
AIBN, CCl4, reflux, 5 h; (d) CH3COONa, CH3COOH, reflux, 8 h,
84.4%; (e) ethylenediamine, anhydrous acetonitrile, room temp.,
12 h, 63.6%
To examine the feasibility of bis(coumarinyl) Schiff base with reference to quinine sulfate (see the Supporting Infor-
1 as a chemodosimeter for Fe3+, we first investigated its mation).[17] This low-fluorescence character of free 1 is ap-
fluorescence character in the absence and presence of Fe3+
.
parently attributed to a PCT process (from the electron-
As shown in Figure 1, bis(coumarinyl) Schiff base 1 (5 µ) donating C=N moiety to the coumarin ring), which
was very stable and exhibited no fluorescence variations in quenches the excited state emission of the coumarin fluoro-
the absence of Fe3+ in CH3OH/H2O solution (98:2). By con- phore.[1–3] The fluorescence response of 1 toward increasing
trast, upon treatment with Fe3+ (12 equiv.), a marked en- concentrations of Fe3+ ions is displayed in Figure 2. When
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Eur. J. Org. Chem. 2008, 2689–2692

A Fluorescence Enhanced Chemodosimeter for Fe3+
increasing concentrations of Fe3+ ions were introduced, the
emission of 1 was drastically increased with a fluorescence
enhancement factor (FEF) up to 139.6 and a fluorescence
quantum yield of 0.27.[18] Concomitantly, the addition of
Fe3+ ions also causes a blueshift of the maximal emission
wavelength of the chemodosimeter from 402 to 392 nm
(Figure S1, Supporting Information), which is in good
agreement with the formation of hydrolysis product 4 upon
treatment of 1 with Fe3+. As the changes in fluorescence
intensity are of such magnitude, it may be considered that
the fluorescence emission is “switched off” in 1 and
“switched on” upon the addition of Fe3+
.
Figure 3. (a) Emission response of 1 (5 µ) to different metal ions
(12 equiv.); (b) fluorescence enhancement factors (FEF) of 1 (5 µ)
upon addition of the various metal ions (12 equiv.). Excitation and
emission were at 330 and 392 nm, respectively..
Figure 2. Emission spectra of 1 (5 µ) upon the addition of Fe3+
(0, 0.1, 1, 3, 5, 7, 9, 12, 15 equiv.). Excitation at 330 nm.
Na+ and K+ have virtually no effect on Fe3+ detection.
Interestingly, when Fe3+ (12 equiv.) was introduced to
chemodosimeter 1 in the presence of Cu2+ (36 equiv.), only
15-fold fluorescence enhancement was observed, which is
much lower than that for Fe3+ alone. This is in accordance
To investigate the selectivity, representative ions such as
Na+, K+, Ca2+, Mg2+, Al3+, Fe3+, Fe2+, Co2+, Ni2+, Zn2+
,
Cd2+, Cu2+, Hg2+ and Mg2+ were treated with 1 in CH3OH/
H2O solution (98:2). Changes in the fluorescence spectra
of 1 (5 µ) upon the addition of metal ions are shown in
Figure 3a. Chemodosimeter 1 only exhibits negligible fluo-
rescence variations in the presence of Na+, K+, Ni2+ or
with the quenching nature of Cu2+ [2,19]
Thus, the inter-
.
ference for fluorescence detection of Fe3+ in the presence of
other competing metal ions except Cu2+ is insignificant.
Co2+ (12 equiv.), whereas Fe2+, Al3+, Cd2+, Mg2+, Mn2+
,
Zn2+, Hg2+ and Ca2+ induce a minimum fluorescence en-
hancement. However, Cu2+ quenched approximately 73%
of the fluorescence emission. This is attributed to a quench-
ing effect of the Cu2+ ions.[2,19] The FEF values of chemo-
dosimeter 1 responding to different metal ions are shown
in Figure 3b. It can be seen that Fe2+, Al3+, Cd2+, Mg2+
,
Mn2+, Zn2+, Hg2+ and Ca2+ induce about 4.7-, 7.6-, 6.8-,
6.2-, 4.8-, 4.1-, 3.5- and 3.4-fold increase in fluorescence,
respectively. However, Fe3+ results in the largest fluores-
cence enhancement with a FEF up to 139.6-fold, which in-
dicates that 1 is highly selective towards Fe3+ over other
metal ions tested. This could be explained by the fact that
the pKa of Fe3+ is much lower than those of other metal
ions surveyed.[10]
Figure 4. Fluorescence response of 1 (5 µ) to Fe3+ (12 equiv.) in
the presence of other competing metal ions (36 equiv.). Excitation
and emission were at 330 and 392 nm, respectively..
The interference of typical alkali, alkaline-earth and
transition-metal ions to the fluorescence detection of Fe3+
was also investigated. Fe3+ (12 equiv.) was added to chemo-
dosimeter 1 (5.0 µ) in the presence of related metal ions
(36 equiv.). Apparently, Hg2+, Mg2+, Mn2+ and Ni2+ show
only very mild interference in the detection of Fe3+ (Fig-
Conclusions
We described a fluorescence turn-on chemodosimeter for
ure 4). By contrast, Ca2+, Cd2+, Co2+, Fe2+, Zn2+, Al3+
,
Fe3+ based on metal-promoted hydrolysis of bis(coumari-
Eur. J. Org. Chem. 2008, 2689–2692
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W. Lin, L. Yuan, J. Feng, X. Cao
SHORT COMMUNICATION
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nyl) Schiff base. The chemodosimeter was readily synthe-
sized in four steps from 2,4-dihydroxybenzaldehyde. The
addition of Fe3+ to 1 induced about 140-fold fluorescence
enhancement. In addition, 1 is highly selective to Fe3+ over
other metal ions. Furthermore, most of the related metal
ions exhibit negligible detection interference. Thus, 1 devel-
oped herein possess favourable features for effective applica-
tions in environmental analysis. The future efforts will focus
on improving its water solubility by structural modifica-
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biological applications. As most transition-metal ions pos-
sess intrinsic fluorescence quenching properties, it is very
challenging to develop their sensors with fluorescence en-
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fluorescence turn-on chemodosimeters for other transition-
metal ions by employing a particular metal-facilitated reac-
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Supporting Information (see footnote on the first page of this arti-
cle): Detailed experimental procedures and full characterization
data for all compounds synthesized, and some spectra of the probe.
Acknowledgments
Funding was partially provided by the Scientific Research Founda-
tion for the Returned Overseas Chinese Scholars, State Education
Ministry (2007-24), the Key Project of Chinese Ministry of Educa-
tion and the Hunan University research funds.
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[18] According to Figure 2, as little as 1 equiv. of Fe3+ is able to
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Received: January 23, 2008
Published Online: March 28, 2008
Publication delayed on authors’ request
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Eur. J. Org. Chem. 2008, 2689–2692