A BODIPY-based fluorescent chemodosimeter for Cu(ii) driven by an oxidative dehydrogenation mechanism

Article abstract of DOI:10.1039/c0cc04069j

A boradiazaindacene (BODIPY) derivative containing a simple NO bidentate ligand shows a Cu²⁺-selective fluorescence in aqueous media. This is promoted via a coordination of Cu²⁺ followed by oxidative dehydrogenation of an amine moiet

Full text of DOI:10.1039/c0cc04069j

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A BODIPY-based fluorescent chemodosimeter for Cu(II) driven
by an oxidative dehydrogenation mechanismw
Dongping Wang, Yasuhiro Shiraishi* and Takayuki Hirai
Received 25th September 2010, Accepted 20th December 2010
DOI: 10.1039/c0cc04069j
A boradiazaindacene (BODIPY) derivative containing a simple
NO bidentate ligand shows a Cu2+-selective fluorescence in
aqueous media. This is promoted via a coordination of Cu2+
followed by oxidative dehydrogenation of an amine moiety,
Scheme 1 Cu2+-promoted dehydrogenation model for amine.8,9
of a transition metal cation such as Cu2+ 7
As shown in
leading to a formation of a fluorescent Cu+–Schiff base complex.
.
The design of fluorescent probes for selective detection of Cu2+
has attracted much attention because Cu2+ is a significant
environment pollutant and yet an essential trace element in
biological systems.1 A variety of Cu2+ probes have been proposed;
however, most of the early reported probes show fluorescence
quenching response due to the paramagnetic nature of Cu2+ and
lack sufficient sensitivity.2 Cu2+ probes showing a fluorescence
enhancement response have also been proposed; however, many
of these show poor binding selectivity to Cu2+ over other cations
such as Fe3+ and Hg2+ and lack sufficient selectivity.3
Recently, reaction-based Cu2+ probes that are called chemo-
dosimeters have attracted a great deal of attention,4–6 as an
alternative to the classical chelation-based probes. In most cases,
nonemissive chemodosimeter molecules are converted to the emis-
sive ones via irreversible chemical reactions promoted by Cu2+. A
large number of fluorescent Cu2+ chemodosimeters have been
proposed based on several Cu2+-promoted reactions such as
hydrolysis of lactone,4a esters,4b–e hydrazone,4f lactams,4g,h and
amide;4i and oxidation of dihydrorosamine,5a phenothiazine,5b
catechol,5c phenol,5d and DNA.5e A few chemodosimeters employ
other reactions.6 Many of these, however, suffer from several
issues. They (i) act only in pure organic solvents or solutions with
very small amounts of water (o20%);4d,i,5b–d,6 (ii) require specific
reaction conditions such as high temperature,4a–c,6c acidic4f or basic
pH;4a and, (iii) show low Cu2+ selectivity in the presence of other
metal cations.4e,g–i,5e,6a,c To the best of our knowledge, there is only
one report of the Cu2+ chemodosimeter which addresses these
issues.5a The design of chemodosimeters based on a new
Cu2+-selective reaction is thus the current focus of attention.
Oxidative dehydrogenation of amine to imine is a well
known reaction in biochemistry, promoted by coordination
Scheme 1, a tetrahedral coordination of amine-containing
ligands with Cu2+ gives rise to the corresponding imine
complexes in the presence of the molecular oxygen at room
temperature,8,9 where the reaction sometimes involves reduction
of Cu2+ center to Cu+.9 Although the detailed mechanism is still
unclear, cooperative oxidation by Cu2+ and O2 is commonly
thought to be involved in the reaction.
Herein, we report that the Cu2+-promoted dehydrogenation
of amine allows selective chemodosimetric detection of Cu2+ in
aqueous media with neutral pH at room temperature. We
employ a ligand 110 (Fig. 1), consisting of a BODIPY dye11
as a fluorescent signaling unit and a simple NO bidentate ligand
as a coordination site for Cu2+.8 The ligand 1 is nonfluorescent,
but Cu2+ addition shows a strong fluorescence enhancement.
This is promoted via a coordination of Cu2+ with 1 followed by
dehydrogenation of amine moieties, leading to a formation of a
fluorescent Cu+–Schiff base complex.
The ligand 1 was obtained according to the procedure
described previously.10 Compounds 2–4 (Fig. 1) were synthesized
as reference materials, which were obtained with >76% yields
(see ESIw) and fully characterized by 1H NMR, 13C NMR,
and MS analysis (Fig. S1–S9, ESIw).
Fig. 2a shows the fluorescence spectra (lex = 510 nm) of 1
(5 mM) measured in a buffered MeCN/water mixture (1/1 v/v;
HEPES 100 mM; pH 7.0) with 20 equiv. of the respective
metal cation in an aerated condition. Without cation, 1 shows
Research Center for Solar Energy Chemistry, and Division of
Chemical Engineering, Graduate School of Engineering Science,
Osaka University, Toyonaka 560-8531, Japan.
E-mail: shiraish@cheng.es.osaka-u.ac.jp; Fax: +81 6 68506273;
Tel: +81 6 68506271
w Electronic supplementary information (ESI) available: General
method, synthesis, Fig. S1–S23. See DOI: 10.1039/c0cc04069j
Fig. 1 Chemodosimeter 1 and reference compounds 2–4.
Chem. Commun., 2011, 47, 2673–2675 2673
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Fig. 2 (a) Fluorescence spectra (lex = 510 nm) of 1 (5 mM) measured
in a MeCN/water mixture (1/1 v/v; HEPES 100 mM; pH 7.0) with
20 equiv. of respective metal cation in an aerated condition. The
spectra were measured after stirring the solution with cation for
20 min. (b) The ratio of fluorescence intensity (FI/FI0) of 1. The
absorption spectra are summarized in Fig. S10, ESI.w
Fig. 4 Absorption titration of 1 (5 mM) with Cu2+ (0–30 equiv.) in a
MeCN/water mixture (1/1 v/v; HEPES 100 mM; pH 7.0).
intensity and Cu2+ amount at the range of 0.05–4 equiv.,
which corresponds to 0.25–20 mM Cu2+. The detection limit,
0.25 mM, is below the maximum permissive level of Cu2+ in
drinking water (B20 mM) set by the U.S. Environmental
Protection Agency. The fluorescence increase of 1 after addition
of Cu2+ is saturated within 20 min (Fig. S14, ESIw), suggesting
that 20 min assay time is enough for analysis.
almost no fluorescence, where the emission quantum yield (FF)
is 0.002. This is because, as usually observed,1b the electron
transfer from the amine nitrogen to the excited state BODIPY
moiety quenches the emission. Addition of Cu2+, however,
creates a strong fluorescence at 520–680 nm (FF = 0.095). As
shown in Fig. 2b, the fluorescence enhancement upon Cu2+
addition is more than 256-fold. In contrast, other metal cations
scarcely show fluorescence enhancement (FF o0.005). It is
noted that the fluorescence response of 1 to Cu2+ is unaffected
by other metal cations (Fig. S11, ESIw), indicating that 1 detects
Cu2+ selectively even in the presence of other cations. The
Cu2+-induced fluorescence enhancement of 1 occurs at pH 5–9
(Fig. S12, ESIw), suggesting that 1 enables Cu2+ detection at a
physiological pH range. In addition, counter anions of Cu2+ do
not affect the response of 1 (Fig. S13, ESIw). Furthermore, the
fluorescence emission obtained upon Cu2+ addition is stable;
the intensity is kept for at least 30 days even left in an aerated
condition at room temperature.
Fig. 4 shows the result of absorption titration of 1. Without a
cation, 1 shows an absorption band at 605 nm, assigned to the
BODIPY moiety.11 The Cu2+ addition leads to a decrease in this
band with a blue shift (584 nm).12 The spectral change almost
stops upon addition of 20 equiv. of Cu2+, which is similar to the
fluorescence titration result (Fig. 3). Adding excess amount of
EDTA to the solution does not show further spectral change
(Fig. S16, ESIw), indicating that 1 reacts with Cu2+ irreversibly.
The Cu2+-induced emission enhancement is due to the
formation of a 1–Cu+ 2 : 1 complex containing two imine
moieties (Scheme 2). This is promoted via a coordination of
Cu2+ with two 1 molecules followed by dehydrogenation by
Cu2+ and O2. The reaction of 1 with Cu2+ in a 2 : 1
stoichiometry is confirmed by Job’s plot (Fig. S18, ESIw);
the emission intensity shows a maximum at X = 0.33
(=[Cu2+]/([Cu2+] + [1]). The solution of 1 treated with
Cu2+ was extracted with CH2Cl2, washed with water, and
concentrated by evaporation. Fig. 5 shows the IR spectra of 1
and the obtained 1–Cu complex. 1 shows two distinctive bands
assigned to the O–H and N–H stretching vibration at ca.
3450 cmÀ1. In contrast, the 1–=Cu complex does not show
these bands, but shows a new band at 1618 cmÀ1, assigned to
the imine (C=N) moiety. This band is also observed for a
Fig. 3 shows the result of fluorescence titration of 1. The
Cu2+ addition leads to an increase in the 596 nm fluorescence,
and the increase is saturated with 20 equiv. of Cu2+. As shown
in the inset, a linear relationship is observed between the
Fig. 3 Fluorescence titration (lex = 510 nm) of 1 (5 mM) with Cu2+
(0–30 equiv.) in a MeCN/water mixture (1/1 v/v; HEPES 100 mM;
pH 7.0). Each spectrum was obtained after stirring the solution with
Cu2+ for 20 min. (inset) Change in intensity at 596 nm.
Scheme 2 Proposed mechanism for the Cu2+-promoted fluorescence
enhancement of 1. The optimized geometry of the 1–Cu+ 2 : 1
complex (right) is shown in Fig. S17, ESI.w
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2674 Chem. Commun., 2011, 47, 2673–2675
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This work was supported by the Grant-in-Aid for Scientific
Research (No. 21760619) from the Ministry of Education,
Culture, Sports, Science and Technology, Japan (MEXT).
Notes and references
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moieties.13 As shown in Fig. S20 (ESIw), ESR analysis of the
complex shows no signal for Cu2+, indicating that the complex
involves Cu+. These findings suggest that, as shown in
Scheme 2 and observed for related amine-containing ligands,9
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Cu+–Schiff base complex via an oxidative dehydrogenation
of two amine moieties by Cu2+ and O2.14 The dehydrogena-
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from the nitrogen atoms to the excited state BODIPY moiety1b
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The reference compound 2 with an imine moiety (Fig. 1)
shows a strong emission (FF = 0.19). Addition of Cu+ to 2,
however, shows almost no spectral change (Fig. S22, ESIw).
This is because 2 scarcely coordinates with Cu+ due to the low
affinity to the phenolic –OH group.15 In contrast, addition of
Cu2+ to 2 strongly quenches the emission. This is probably
due to the paramagnetic nature of Cu2+ 16
Other reference
.
7 F. R. Keene, Coord. Chem. Rev., 1999, 187, 121.
compounds 3 and 4 that do not contain –OH groups (Fig. 1)
show very weak emission enhancement upon Cu2+ addition
(Fig. S22, ESIw), indicating that the strengthened coordination
of Cu2+ with –OH is crucial for amine dehydrogenation. These
data also support the proposed mechanism (Scheme 2).
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It is noted that the Cu2+-promoted emission enhancement of
1 depends strongly on solvents. Addition of Cu2+ to 1 in water
(pH 7) containing DMSO, THF, acetone, MeOH, DMF, or
dioxane (50%) shows almost no emission enhancement. This is
probably because Cu+ species is unstable in these solvents,
although MeCN stabilizes Cu+ species.17 In addition, as shown
in Fig. S23 (ESIw), the 596 nm fluorescence does not appear in
pure MeCN, but an increase in the water content leads to an
enhancement. This is probably because water catalyzes the
Cu2+–amine redox process. Although the detailed role of water
cannot be identified at this stage, similar water effect is observed
in the dehydrogenation of an amine ligand in the Fe3+ complex
system.18 These findings suggest that both MeCN and water are
necessary for the Cu2+-induced fluorescence enhancement of 1.
In summary, we found that a BODIPY derivative, 1,
containing a simple NO bidentate ligand behaves as a fluores-
cent chemodosimeter for Cu2+. Although the detailed analysis
for the dehydrogenation mechanism still remains to be
clarified, the simple ligand design may contribute to the design
9 V. Amendola, L. Fabbrizzi, E. Mundum and P. Pallavicini, Dalton
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12 The long wavelength absorption is probably due to the diffraction by
the aggregates of 1–Cu complexes due to the low solubility; the
absorption disappears with a rise in temperature (Fig. S15, ESIw).
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in aqueous media.: R. Hu, E. Lager, A. Aguilar-Aguilar, J. Liu,
J. W. Y. Lam, H. H. Y. Sung, I. D. Williams, Y. Zhong,
K. S. Wong, E. Pena-Cabrera and B. Z. Tang, J. Phys. Chem. C,
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13 1H NMR analysis further confirms the presence of an imine moiety
(Fig. S19, ESIw). The reaction of 1 with Cu2+ leads to a disappearance
of CH2–NH protons at d 4.45 and 4.10 ppm and a generation of new
signal at d 8.49 ppm assigned to the imine moiety.
14 O2 is important for this reaction. The fluorescence intensity of 1 in
the presence of Cu2+ measured under argon is much lower than
that measured under air (Fig. S21, ESIw).
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18 V. L. Goedken and D. H. Busch, J. Am. Chem. Soc., 1972, 94, 7355.
of the more efficient and useful chemodosimeter for Cu2+
.
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