A selective colorimetric and fluorometric ammonium ion sensor based on the H-aggregation of an aza-BODIPY with fused pyrazine rings

Article abstract of DOI:10.1039/c1cc15746a

The synthesis of a novel aza-BODIPY dye functionalized with fused pyrazine rings, suitable for use as a selective colorimetric and fluorometric sensor for NH₄⁺, is outlined. In addition to significant fluorescence quenching, an obvio

Full text of DOI:10.1039/c1cc15746a

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COMMUNICATION
A selective colorimetric and fluorometric ammonium ion sensor based on
the H-aggregation of an aza-BODIPY with fused pyrazine ringsw
Hanzhuang Liu,ab John Mack,b Qiuli Guo,a Hua Lu,c Nagao Kobayashi*b and Zhen Shen*a
Received 17th September 2011, Accepted 7th October 2011
DOI: 10.1039/c1cc15746a
The synthesis of a novel aza-BODIPY dye functionalized with
fused pyrazine rings, suitable for use as a selective colorimetric
and fluorometric sensor for NH4+, is outlined. In addition to
significant fluorescence quenching, an obvious colorimetric
change from green to red-pink is observed enabling facile
+
‘‘naked-eye’’ detection of NH4
.
Boradiazaindacenes (BODIPY dyes, BDPs, difluorobora-
dipyrromethenes, etc.) have been studied extensively,1 since their
spectroscopic properties are suitable for many applications,2
including use in ion sensing and signalling,3 and as fluorescent
labels in biomolecules.4 The absorption and emission bands
associated with the S1 state of the unmodified BODIPY parent
complex lie at ca. 500 nm. While this is satisfactory for many
applications, a red shift of the absorption and fluorescence
maxima into the red end of the visible region, or still further
into the near-infrared, would be advantageous in others, given
the recent advances in optical techniques for imaging, micro-
arrays, and electrophoresis, and the Rayleigh scattering and
pigmentation problems that are often encountered with
biological samples.5
Scheme 1 Synthetic procedures for aza-BODIPY 3. (i) H2O/ethanol
(2 : 3), acetic acid, reflux; (ii) dry diethyl ether, RT, 1 h; (iii) BF3ÁOEt2,
triethylamine, dry CH2Cl2, reflux.
binding groups can no longer be introduced at the meso-
carbon. Recent advances in aza-BODIPY synthesis based on
the use of phthalonitrile precursors2 have enabled the facile
synthesis of fused ring expanded aza-BODIPYs, which
considerably enhances the scope for introducing structural
modifications that enhance the ion binding properties.
Many different approaches have been explored to obtain
this red shift of the main BODIPY absorption band, including
the introduction of aromatic or heteroaromatic rings as sub-
stituents at the 3-, 5- and/or 1-,7-positions on the pyrrole
moieties6 and aromatic ring fusion.7 Replacing the meso-
carbon atom with an aza-nitrogen atom to form an
aza-BODIPY8 typically results in a ca. 90 nm red shift of the
main absorption band with respect to the analogous non-
substituted BODIPY derivatives.9 Until recently a key draw-
back in the context of sensor applications was that suitable ion
In this communication, we report the rational design and
synthesis of a novel aza-BODIPY, 3, containing two fused
pyrazine rings (Scheme 1). The rationale for introducing fused
pyrazine rings is that it results in the presence of close-lying
nitrogen atoms, which can potentially bind large cations in the
meso-pocket or between neighboring aza-BODIPY complexes.
A survey of the interaction between 3 and a wide range of
metal ions subsequently demonstrated that marked changes in
the optical properties are only observed for the NH4+ ion in a
manner which facilitates its colorimetric and fluorometric
detection. The aza-diisoindolmethine precursor, 2, was prepared
by adding a phenyl Grignard reagent to a suspension of
5,6-diethylpyrazine-2,3-dicarbonitrile, 1, in diethyl ether
(Scheme 1 and ESIw) according to the published procedures
for benzo-fused aza-BODIPYs.2 The corresponding boron
difluoride complex was obtained from a reaction with
borondifluoride diethyl ether complexes and a base under reflux
in CH2Cl2. The structure of 3 was confirmed by 1H NMR
spectroscopy, MS and single-crystal X-ray diffraction analysis.
A single crystal of 3 suitable for X-ray structural analysis
was obtained by diffusion of hexane into a solution of 3 in
CH2Cl2 (Fig. 1 and ESIw). The structure is comparable to
a State Key Laboratory of Coordination Chemistry, Nanjing National
Laboratory of Microstructures, Nanjing 210093, P. R. China.
E-mail: zshen@nju.edu.cn; Fax: +86 (0)25-83314502;
Tel: +86 (0)25-83686679
b Department of Chemistry, Graduate School of Science, Tohoku
University, Sendai 980-8578, Japan.
E-mail: nagaok@m.tohoku.ac.jp; Fax: +81 (0)22-795-7719
c Key Laboratory of Organosilicon Chemistry and Material
Technology, Ministry of Education, Hangzhou Normal University,
Hangzhou, 310012, P. R. China
w Electronic supplementary information (ESI) available: 1H NMR
spectra, X-ray analysis of aza-BODIPY 3, synthesis details, etc.
CCDC 843443. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c1cc15746a
c
12092 Chem. Commun., 2011, 47, 12092–12094
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Fig. 1 Front ORTEP view of the molecular structure of 3 with the
thermal ellipsoids set at 30% probability (left). A one-dimensional
chain of 3 viewed along the c axis (right).
Fig. 3 Absorption intensity observed at 685 nm upon addition of
various metal ions (black) and the NH4+ ion (red) to 10 mM solutions
of 3 in THF solution (left). Changes in the absorption spectrum of
aza-BODIPY 3 (10 mM in THF) as the ammonium acetate concentration
is increased. The inset shows the solution colour before (green) and after
those reported previously for other aza-BODIPY compounds.9b
The boron atom is coordinated in a tetrahedral geometry by
two nitrogen and two fluorine atoms. The indacene plane of 3
is nearly planar. The average deviation from the mean plane is
only 0.1181 A. The neighboring aza-BODIPY molecules are
linked by intermolecular C–HÁ Á ÁF hydrogen bonds to form a
one dimensional chain along the c axis (Fig. 1). The distance
between neighboring indacene planes is 3.59 A. This indicates
that there is a strong p–p interaction within the chain.
The absorption and fluorescence spectra of 3 in THF (Fig. S3,
ESIw) exhibit the characteristic properties normally antici-
pated for the aza-BODIPY chromophore. An intense absorption
peak is observed at 685 nm with a relatively narrow band
width, which lies 24 nm to the blue of the corresponding
band in the spectrum of the benzo-fused compound, 4.9b The
band in the fluorescence spectrum at 721 nm exhibits mirror
symmetry with the absorption band. The Stokes shift observed
for 3 (36 nm) is significantly larger than that reported for 4
(17 nm).
+
(pink) addition of NH4 (right).
which results from this, causes the blue-shift of the lowest-
energy absorption band relative to that of 4.
Almost no change is observed in the absorption intensity of
3 upon addition of excess of Zn2+, Cd2+, Hg2+, Co2+, Fe3+
,
Fe2+, Ni2+, Mn2+, Cu2+, Mg2+, Na+, Al3+ and Ca2+, but
when NH4+ is added to the THF solution, the typical transition
bands for aza-BDP decrease significantly and a weak broader
band appears at 505 nm instead (Fig. 3). This results in a
visible colorimetric change from green to red-pink. Although
an isosbestic point is observed at 555 nm, the lack of similar
isosbestic points at ca. 480 and 740 nm is consistent with the
presence of at least three different species, since isosbestic
points would be observed across the entire spectrum in the
context of interconversion between two species (Fig. 3).10
+
Turn-off fluorescent detection of the NH4 ion can also be
carried out (Fig. 4).
Molecular orbital (MO) calculations were performed for 3
and 4 using the B3LYP functional with 6-31G (d) basis sets
(Fig. 2). Larger MO coefficients are observed on the pyrazine
moieties of 3 relative to the fused benzene rings of 4 due to the
higher electronegativity of the nitrogen atoms. Since the
HOMO of 3 has significant MO coefficients on all four
pyrazine nitrogen atoms, while the LUMO does not, the
relative stabilization of the HOMO of 3 can be readily
accounted for. The greater HOMO–LUMO band gap value,
The most obvious explanation for the NH4+ mediated color
change and fluorescent quenching is that there is H-aggregation11
+
of the aza-BODIPY. In the absence of the NH4 ion, an
intense S0 - S1 transition associated primarily with the core
aza-BODIPY p-system results in the intense absorption band
with a narrow band width typically observed for BODIPY
+
dyes. Upon addition of the NH4 ion, there is a marked
decrease in the molar absorption coefficient and a broader
band is observed at shorter wavelength and a quenching of the
fluorescence intensity. This is the pattern typically observed
for H-aggregates. Although their solution structures are often
still poorly understood, it is generally accepted that this is due
to face-to-face stacking of the monomer and a parallel alignment
of electric dipole transition moments perpendicular to the axis
+
of stacking.12 The key difference between the NH4 ion and
the metal ions that were studied is the tetrahedral structure due
Fig. 4 Emission spectrum of aza-BODIPY 3 in the presence of
+
Fig. 2 Energy-level diagram for the frontier p-MOs of 3 and 4. The
nodal patterns of each MO are shown at an isosurface value of
0.02 a.u.
increasing NH4 concentration in THF (left, lex = 630 nm).
The emission intensity at 718 nm changes as a function of NH4
+
concentration (right).
c
This journal is The Royal Society of Chemistry 2011
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to the four N–H bonds. This provides scope for hydrogen
bonding similar to that reported previously by Ahn et al. in
the context of an alaninol-derived tripodal oxazoline,13 and
hence for aggregation. If aza-BODIPY complexes are aligned
face-to-face in an opposite direction as is required to avoid steric
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crowding due to the phenyl rings and BF2, an NH4 ion can
potentially interact with the four nitrogen atoms of two pyrazine
rings in a tetrahedral geometry (Fig. S4, ESIw). There is also
scope for hydrogen bonding with the central meso- and pyrrole
nitrogens. H-aggregation is not observed with 4, since hydrogen
bonding is not possible with the peripheral fused benzene rings.
A blue-shifted absorption band is typically observed for
H-aggregates, since only the transition to a higher energy
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predict that even with a relatively limited degree of aggregation
the lowest energy state is greatly stabilized (Fig. S5, ESIw).
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either non-radiative decay is the dominant pathway back to
the ground state for this reason or there is an enhancement of
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In conclusion, the rational design of an aza-BODIPY dye
with fused pyrazine rings provides the first example of the use
of a fused-ring-expanded aza-BODIPY complex as a chemo-
sensor. Highly selective colorimetric and fluorometric detection
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+
of the NH4 ion is observed and the pronounced spectral
changes enable naked-eye detection. The successful rational
design and synthesis of this dye and its apparent H-aggregation
further demonstrate how the flexibility which is introduced by
the use of phthalonitriles as precursors2 can provide scope for
the development of efficient aza-BODIPY chemosensors suitable
for use in the NIR region, despite the absence of the meso-
carbon typically used to incorporate recognition units in the
context of BODIPYs.
Financial support was provided by the National Natural
Science Foundation of China (nos. 20971066 and 21021062),
the Chinese Ministry of Education’s Program for New Century
Excellent Talents in Universities (no. NCET-08-0272), the
Major State Basic Research Development Program of China
(grant nos. 2011CB808704 and 2007CB925103), and a Grant-
in-Aid for Scientific Research on Innovative Areas (no.
20108007, ‘‘pi-Space’’) from the Ministry of Education,
Culture, Sports, Science, and Technology (MEXT), Japan.
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Notes and references
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c
12094 Chem. Commun., 2011, 47, 12092–12094
This journal is The Royal Society of Chemistry 2011