Near-infrared sensing properties of dimethlyamino-substituted BF 2-azadipyrromethenes

Article abstract of DOI:10.1021/ol061171x

The synthesis and sensing characteristics of a new class of organic colorimetric and fluorometric chemosensor which operates in the 850-650 nm spectral region is outlined. Judicious placing of amine substituents on the BF₂-chelated tetraarylaza

Full text of DOI:10.1021/ol061171x

ORGANIC
LETTERS
2006
Vol. 8, No. 16
3493-3496
Near-Infrared Sensing Properties of
Dimethlyamino-Substituted
BF2−Azadipyrromethenes
Shane O. McDonnell and Donal F. O’Shea*
Centre for Synthesis and Chemical Biology, Conway Institute, School of Chemistry and
Chemical Biology, UniVersity College Dublin, Belfield, Dublin 4, Ireland
donal.f.oshea@ucd.ie
Received May 12, 2006
ABSTRACT
The synthesis and sensing characteristics of a new class of organic colorimetric and fluorometric chemosensor which operates in the 850
−
650 nm spectral region is outlined. Judicious placing of amine substituents on the BF2-chelated tetraarylazadipyrromethene chromophore
generates a triple absorption and emission responsive sensor. Dramatic pH responsive absorption and fluorescence changes can be observed
across a broad acidity range, from pH 5 to 6 M HCl, in conjunction with a visible colorimetric change from red to purple to blue.
The development of synthetic routes to organic chromophores
with spectral properties in the near-infrared (NIR) and visible
red spectral regions continues to attract a sustained research
interest due to the lack of suitable classes which could be
tailored to specific applications by peripheral substituent
variations. New chromophore scaffolds with controllable
photophysical properties in the 900-650 nm spectral region
offer potential for exploitation in a diverse range of material
and biological applications, such as optical data storage,1
photoconductors,2 electrochromic devices,3 chemosensors,4
immunoassay labels and bioconjugated probes,5 and in vitro
and in vivo imaging agents.6 We are currently interested in
devising new chromophore platforms which can be adapted
and optimized as biological chemosensors and imaging
agents. Many of the current biological indicators have
operational light input/output wavelengths in the 300-600
nm wavelength range, which often limits their applications
as these spectral regions suffer from strong interference due
to background absorbance and auto-fluorescence from en-
dogenous chromophores in sample media.7 Despite the
optical benefits of utilizing the NIR spectral region for
analytical techniques, there is a surprising paupicity of
(1) Mustroph, H.; Stollenwerk, M.; Bressau, V. Angew. Chem., Int. Ed.
2006, 45, 2016.
(2) Law, K. Y. Chem. ReV. 1993, 93, 449.
(5) Go´mez-Hens, A.; Aguilar-Caballos, M. P. Trends Anal. Chem. 2004,
23, 127.
(6) Ntziachristos, V.; Ripoll, J.; Wang, L. V.; Weissleder, R. Nat.
Biotechnol. 2005, 23, 313.
(3) Rurack, K.; Kollmannsberger, M.; Daub, J. Angew. Chem., Int. Ed.
2001, 40, 385.
(4) For examples, see: (a) Zen, J.-M.; Patonay, G. Anal. Chem. 1991,
63, 2934. (b) Zhang, Z.; Achilefu, S. Chem. Commun. 2005, 5887.
(7) Weissleder, R. Nat. Biotechnol. 2001, 19, 316.
10.1021/ol061171x CCC: $33.50
© 2006 American Chemical Society
Published on Web 07/11/2006

organic compounds which have the desired absorption and
emission properties.8 As such, the development of versatile
synthetic methods to new NIR chromophores has become
an urgent requirement.
The synthesis of 2 was achieved in a facile three-step route
from the R,â-unsaturated ketone 3 (Scheme 1). Addition of
The BF2 chelated-tetraphenylazadipyrromethene 1 and
related structural analogues have recently been reported as
a class of chromophore with high absorption extinction
coefficients (70000-80000 M-1 cm-1) and fluorescence
quantum yields (0.23-0.36) between 650 and 750 nm
(Figure 1).9 In addition, we have shown that this structural
Scheme 1. Synthesis of 2
nitromethane to 3 gave the 1,3-diaryl-4-nitrobutan-1-one 4
in 71% yield after recrystallization from MeOH. Subsequent
generation of the tetraarylazadipyrromethene 5 was achieved
by reflux of 4 with ammonium acetate in ethanol for 24 h.
Filtration of the precipitate from the crude reaction mixture
gave the pure product as a metallic red compound in 47%
yield. Compound 5 was converted to our targeted structure
2 by reaction with boron trifluoride diethyl etherate and
diisopropylethylamine in dichloromethane for 24 h. An
isolated purified yield of 68% was obtained following
chromatography on silica gel.
Analysis of the crystal structure of 2 confirmed the overall
conjugated nature of the chromophore, and as would be
expected, both anilino-substituted rings were virtually co-
planar with the pyrrole rings, thereby predicting a strong
electronic interaction within the chromophore unit (Figure
2, Supporting Information).
Figure 1. BF2-chelated tetraarylazadipyrromethenes.
class can be adapted to act as effective fluorosensors based
upon a photoinduced electron-transfer mechanism.10 These
photophysical characteristics suggest that this structural class
would make an excellent platform from which NIR analogues
could be constructed. This we envisaged could be ac-
complished by substituting the parent chromophore molecule
with two basic amine donors, thereby constructing an electron
donor-acceptor-donor system in which the amine units are
intrinsically connected to the chromophore as shown in 2
(Figure 1). In addition to providing a means of accessing
longer wavelength derivatives, the inclusion of amine sub-
stituents would offer the potential of providing a more
advanced molecular assembly which could generate pro-
nounced photophysical changes as a result of a substrate
recognition event by the amine substituents. It was antici-
pated that this amine receptor-chromophore-amine receptor
design would undergo pronounced spectral changes due to
variance in the internal charge transfer (ICT) properties of
the system in response to acid analyte.11 In due course, this
ICT switching mechanism could potentially be used at
physiological pH in conjunction with a more elaborate amine
receptor to detect metal ions such as Ca2+, Cu2+, and Mg2+.12
(8) For representative examples, see; (a) Tarazi, L.; George, A.; Patonay,
G.; Strekowski, L. Talanta 1998, 46, 1413. (b) Meier, H.; Petermann, R.
HelV. Chim. Acta 2004, 87, 1109. (c) Lee, S.; White, A. J. P.; Williams, D.
J.; Barrett, A. G. M.; Hoffman, B. M. J. Org. Chem. 2001, 66, 461.
(9) (a) Killoran, J.; Allen, L.; Gallagher, J. F.; Gallagher, W. M.; O’Shea,
D. F. Chem. Commun. 2002, 1862. (b) Gorman, A.; Killoran, J.; O’Shea,
C.; Kenna, T.; Gallagher, W. M.; O’Shea, D. F. J. Am. Chem. Soc. 2004,
126, 10619. (c) McDonnell, S. O.; Hall, M. J.; Allen, L. T.; Byrne, A.;
Gallagher, W. M.; O’Shea, D. F. J. Am. Chem. Soc. 2005, 127, 16360. (d)
Gallagher, W. M.; Allen, L. T.; O’Shea, C.; Kenna, T.; Hall, M.; Killoran,
J.; O’Shea, D. F. Br. J. Cancer 2005, 92, 1702. (e) Zhao, W.; Carreira, E.
M. Angew. Chem., Int. Ed. 2005, 44, 1677. (f) Sathyamoorthi, G.; Soong,
M. L.; Ross, T. W.; Boyer, J. H. Heteroatom. Chem. 1993, 4, 603.
(10) (a) Killoran, J.; O’Shea, D. F. Chem. Commun. 2006, 1503. (b)
Hall, M. J.; Allen, L. T.; O’Shea, D. F. Org. Biomol. Chem. 2006, 4, 776.
(c) Hall, M. J.; McDonnell, S. O.; Killoran, J.; O’Shea, D. F. J. Org. Chem.
2005, 70, 5571.
Figure 2. X-ray crystal structure of 2 with thermal ellipsoids drawn
at 50% probability level.
To demonstrate the spectroscopic effects of the amine
substituents, the absorbance characteristics of 2 were com-
(11) For example; Maus, M.; Rurack, K. New J. Chem. 2000, 24, 677.
3494
Org. Lett., Vol. 8, No. 16, 2006

pared to that of the tetraphenyl derivative 1. We were pleased
to record that in organic solvents such as chloroform, 2 had
a wavelength of maximum absorbance of 799 nm and an
extinction coefficient of 87000 M-1 cm-1. Thus, the amine
substituents on 2 provided a striking bathochromatic shift
of 149 nm in comparison to 1 (λmax ) 650 nm and ꢀ ) 79000
M-1 cm-1) (Figure 3). In addition, the longest wavelength
The sharp isosbestic point at 760 nm indicated the formation
of the monoprotonated compound 2-H+. Continuation of the
TFA titration resulted in a stepwise decrease in the 738 nm
band of 2-H+, with the formation of a new absorption band
at 643 nm with a second clear isosbestic point at 667 nm.
This doubly protonated species 2-2H+ has a UV-vis
spectrum that closely matches unfunctionalized 1. The
ratiometric nature of the distinct and well-separated spectral
bands could facilitate in situ monitoring of acid concentration
and remain impervious to environmental interference.13
Gratifyingly, an examination of the fluorescence properties
of 2 revealed a triple emission profile corresponding to the
absorbance spectral properties. Excitation of 2 (at 773 nm)
in chloroform yielded an emission band with a λmax of 823
nm,14 which sequentially decreased upon addition of aliquots
of TFA (Figure 5, red traces). Excitation at 700 nm during
Figure 3. Absorption spectra of 1 in CHCl3 (green λmax ) 650
nm) and 2 in CHCl3 (solid red line λmax ) 799 nm), ethanol (dashed
red line λmax ) 799 nm), and toluene (dotted red line λmax ) 798
nm) (4 × 10-6 M conc).
absorbance band of 2 showed very little solvent dependence
in polar protic or nonpolar solvents (Figure 3).
To explore the absorption spectral responses of 2 to acid
analyte, a chloroform solution of 2 was titrated by the
sequential addition of aliquots of trifluoroacetic acid (TFA)
which revealed spectacular spectral shifts (Figure 4). Upon
Figure 5. Normalized fluorescence spectra of 2 in chloroform (5
× 10-7 M) titrated with aliquots of TFA. Red trace (excitation at
773 nm, λmax emission ) 823 nm), black traces (excitation at 700
nm, λmax emission ) 753 nm), blue trace (excitation at 630 nm,
λmax emission ) 668 nm). Slit widths 10 nm.
this titration revealed a concommital appearance of an
emission band at 753 nm (Figure 5, black traces). Continu-
ation of TFA addition resulted in the disappearance of the
753 nm emission band and the emergence of a new emission
band at 668 nm upon excitation at 630 nm (Figure 5, blue
traces). The intensity of the emissions at 823 and 753 nm
for 2 and 2-H+ respectively were significantly less than the
668 nm emission potentially due to the charge-transfer
properties of these species. This triple emission profile offers
the basis for ratiometric fluorosensing applications.13
As many sensing applications are conducted in an aqueous
environment, 2 was encapsulated with the neutral surfactant
Cremophor EL (CrEL) to form stable aqueous solutions. In
the aqueous formulated solutions, the starting absorbance
Figure 4. Absorbance TFA titration of 2 in CHCl3 (3.75 × 10-6
M). Isosbestic points at 666 and 760 nm.
addition of TFA, a stepwise disappearance of the 799 nm
band and formation of a new band at 738 nm was observed.
(13) For examples of ratiometric sensors, see: (a) Mello, J. V.; Finney,
N. S. Angew. Chem., Int. Ed. 2001, 40, 1536. (b) Choi, K.; Hamilton, A.
D. Angew. Chem., Int. Ed. 2001, 40, 3912. (c) Xu, Z.; Qian, X.; Cui, J.
Org. Lett. 2005, 7, 3029.
(12) Hartley, J. H.; James, T. D.; Ward, C. J. J. Chem. Soc., Perkin Trans.
1 2000, 3155.
(14) The emission intensity in ethanol was significantly lower when
compared to chloroform and toluene (Supporting Information).
Org. Lett., Vol. 8, No. 16, 2006
3495

maximum of 2 was recorded at 818 nm with emission at
826 nm, a small bathochromic shift when compared to
organic solvents (Supporting Information). Evaluation of the
spectral features during aqueous hydrochloric acid titration
revealed them to be very similar to those observed in
chloroform (Supporting Information). A plot of absorbance
intensity versus pH and molarity of aqueous HCl is shown
in Figure 6. The profiles clearly map out the spectral
Figure 7. Fluorescence titration responses of 2 at 832 nm (red,
b), 779 nm (black, 9), and 698 nm (blue 2, shown at one-tenth
peak intensity). The wavelengths shown were chosen for maximum
signal separation and clarity.
A plot of acidity versus fluorescence response shown in
Figure 7 demonstrates the ratiometric nature of the changes.13
A starting λmax of emission at 826 nm was observed to
decrease with addition of aqueous acid, with a corresponding
increased emission at 779 nm, which upon continuing the
titration decreased, leading to the final emission of the 2-2H+
at 673 nm.
In summary, a new class of NIR/vis red ratiometric triple
channel colorimetric and triple channel fluorometric sensor
has been developed with potential to be exploited and adapted
to suit a diverse range of analytical, imaging, and material
applications. Specifically, 2 could find direct application as
a multiresponsive high acidity indicator.15
Figure 6. Absorption acidity responses of 2: red profile (red, b)
(λmax ) 818 nm), black profile (black, 9) (λmax ) 753 nm), blue
profile (blue, 2) (λmax ) 653 nm), and corresponding visible color
changes for 2 (red), 2-H+ (purple), and 2-2H+ (blue). Crossover
points at pH 1.5 and 3.4 M HCl.
Acknowledgment. S.O.M.D. thanks the Irish Research
Council for Science, Engineering and Technology for a
studentship. Funding support from the Program for Research
in Third-Level Institutions administered by the HEA is
acknowledged. We thank Dr. D. Rai of the CSCB Mass
Spectrometry Centre and Dr. H. Mueller-Bunz of the UCD
Crystallographic Centre for analyses.
absorbance changes during the titration from pH ) 5 to 6
M HCl and highlight the ratiometric nature of the spectral
changes, with two distinct crossover points at pH 1.5 and
3.4 M HCl. In addition to the NIR spectral changes, a
sequence of visible color changes also took place during the
titration. The starting color of a pH neutral solution of 2
was red, which visibly changed to purple upon the generation
of 2-H+ and then to blue upon formation of 2-2H+ (Figure
6). The first red to purple color change can be attributed to
the spectral changes in the 500-600 nm spectral region
occurring in conjunction with the decrease in intensity of
the longer wavelength band at 818 nm and the blue color
corresponds to the absorption band at 653 nm (Supporting
Information). The disappearance and appearance of fluores-
cence emissions in response to the titration were comparable
to those observed in chloroform (Supporting Information).
Supporting Information Available: Synthetic proce-
dures, analytical data, and NMR spectra for 2, 4, and 5.
Absorbance spectra in CrEL and emission spectra in ethanol,
toluene, and water/CrEL. X-ray crystallographic data of 2.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL061171X
(15) (a) Noire, M. H.; Bouzon, C.; Couston, L.; Gontier, J.; Marty, P.;
Pouyat, D. Sens. Actuators B 1998, 51, 214. (b) Lin, J. Trends Anal. Chem.
2000, 19, 541.
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Org. Lett., Vol. 8, No. 16, 2006