Near-infrared nitrofluorene substitued aza-Boron-dipyrromethenes dyes

Article abstract of DOI:10.1021/ol102701v

The synthesis, spectroscopic properties, and TD-DFT calculations of new aza-Boron-dipyromethene dyes featuring pendant nitrofluorenylethynyl substituents are described. This functionalization allows for moving the luminescence in the NIR, conserving a good quantum yield efficiency.

Full text of DOI:10.1021/ol102701v

ORGANIC
LETTERS
2011
Vol. 13, No. 1
22-25
Near-Infrared Nitrofluorene Substitued
Aza-Boron-dipyrromethenes Dyes
Quentin Bellier, Sarah Pe´gaz, Christophe Aronica, Boris Le Guennic,
Chantal Andraud,* and Olivier Maury*
UniVersite´ de Lyon, ICL, CNRS - Ecole Normale Supe´rieure de Lyon, 46 alle´e d’Italie,
Lyon 69007, France
chantal.andraud@ens-lyon.fr; oliVier.maury@ens-lyon.fr
Received September 30, 2010
ABSTRACT
The synthesis, spectroscopic properties, and TD-DFT calculations of new aza-Boron-dipyromethene dyes featuring pendant nitrofluorenylethynyl
substituents are described. This functionalization allows for moving the luminescence in the NIR, conserving a good quantum yield efficiency.
Previously confined to restricted areas (e.g., optical recording,
laser printing and filters),1 near-infrared (NIR) dyes have
found these last years new applications in several important
fields such as bioimaging, sensing and photodynamic therapy
or photovoltaics, organic light emitting diodes, advanced
optoelectronics, and nonlinear optics.2 The emergence of
these technologies triggered the design of new NIR chro-
mophores featuring optimized spectroscopic properties in the
700-1200 nm spectral range. In this context, particular
attention has been focused on NIR luminescent dyes for in
ViVo microscopy imaging applications.2c Indeed, the NIR
region is less absorbed and scattered by biological tissues,
allowing deeper penetration and higher contrast. However,
the emission red-shift up to the NIR is generally accompanied
by a strong decrease of the quantum yield, so a great
challenge is to design chromophores featuring high quantum
yield (Φ) beyond 700 nm. In this spectral range, cyanine
dyes are the most frequently used probes, and some of them
are commercially available despite their rather modest
quantum yield and photostability.1,2 Alternatively, Boron-
dipyrromethene dyes (A, Figure 1) have emerged as a
cyanine subclass featuring sharp fluorescence emission band
with a high quantum yield and higher photostability in the
biological environment.3 Except in a few cases,3c their
(1) (a) Fabian, J.; Nakazumi, H.; Matsuoka, M. Chem. ReV. 1992, 92,
1197–1226. (b) Mishra, A.; Behera, R. K.; Behera, P. K.; Mishra, B. K.;
Behera, G. B. Chem. ReV. 2000, 100, 1973–2011.
(2) For recent reviews see: (a) Qian, G.; Wang, Z. Y. Chem. Asian J.
2010, 5, 1006–1029. (b) Kulinich, A. V.; Ishchenko, A. A. Russ. Chem.
ReV. 2009, 78, 141–162. (c) Kiyose, K.; Kojima, H.; Nagano, T. Chem.
Asian J. 2008, 3, 506–515. (d) Bouit, P.-A.; Maury, O.; Andraud, C.
Nonlinear Opt., Quantum Opt. 2008, 38, 245–258.
10.1021/ol102701v  2011 American Chemical Society
Published on Web 12/03/2010

intramolecular B-O six members rings (E, ∆λem ) 67 nm).7
Unfortunately, this interesting NIR displacement of the
spectroscopic properties was obtained with a significant
decrease of the quantum yield efficiency.6,7
Here, we show that extension of the conjugated pathway
in absence of any electron-donating fragment results in a
marked red-shift of the emission conserving the quantum
yield efficiency. To that end, we take advantage of the
versatile aza-Boron-dipyromethene structure to substitute the
1/7 (7a) or 3/5 (7b) positions by nitrofluorenylethynyl
moieties (Figure 1). The synthesis, characterization, and
photophysical properties are described and interpreted on the
basis of time-dependent density functional theory (TD-DFT)
calculations.
Scheme 1. Synthesis of Chromophores
Figure 1. Different strategies envisaged to displace the absorption
and the emission to the NIR spectral range.
absorption and emission are located in the visible range.
Recent studies have shown that it is possible to move the
photophysical properties to the red only by substituting the
meso-carbon by a nitrogen atom (the aza-Boron-dipy-
romethene dyes B, Figure 1).4b In this family, the compound
C functionalized with electro-donating methoxy group
exhibited a 715 nm emission with a good 0.36 quantum
yield.4 This chromophore is now the benchmark of the family
and was successfully used as bioconjugate or bioprobes for
imaging or sensing applications.5 With C as reference,
additional NIR bathochromic shifts were achieved upon
rigidification of the aza-Boron-dipyromethene skeleton either
by annelation (D, ∆λem ) 36 nm)6 or by formation of
(3) (a) Ulrich, G.; Ziessel, R.; Harriman, A. Angew. Chem., Int. Ed.
2008, 47, 1184–1201. (b) Loudet, A.; Burgess, K. Chem. ReV. 2007, 107,
4891–4932. (c) Umezawa, K.; Nakamura, Y.; Makino, H.; Citterio, D.;
Suzuki, K. J. Am. Chem. Soc. 2008, 130, 1550–1551. (d) Descalzo, A. B.;
Xu, H.-J.; Shen, Z.; Rurack, K. Ann. N.Y. Acad. Sci. 2008, 1130, 164.
(4) (a) Killoran, J.; Allen, L.; Gallagher, J. F.; Gallagher, W. M.; O’Shea,
D. F. Chem. Commun. 2002, 1862–1863. (b) Gorman, A.; Killoran, J.;
O’Shea, C.; Kenna, T.; Gallagher, W. M.; O’Shea, D. F. J. Am. Chem.
Soc. 2004, 126, 10619–10631.
The synthesis of the target compounds 7a,b (Scheme 1)
involves as key step a Sonogashira cross-coupling reaction
between nitrofluoreneacetylide and an iodo or bromo-
functionalized intermediate. In this reaction, starting from
aza-Boron-dipyrromethenes 5a-c results in the loss of the
BF2 fragment, therefore the aza- dipyrromethenes 4a-d were
used as precursors. These latter synthons were prepared using
(5) (a) Tasior, M.; O’Shea, D. F. Bioconjugate Chem. 2010, 21, 1130–
1133. (b) Tasior, M.; Murtagh, J.; Frimannsson, D. O.; McDonnell, S. O.;
O’Shea, D. F. Org. Biomol. Chem. 2010, 8, 522–525. (c) Murtagh, J.;
Frimannsson, D. O.; O’Shea, D. F. Org. Lett. 2009, 11, 5386–5389. (d)
Palma, A.; Tasior, M.; Frimannsson, D. O.; Vu, T. T.; Me´allet-Renault,
R.; O’Shea, D. F. Org. Lett. 2009, 11, 3638–3641.
(6) Zhao, W.; Carreira, E. M. Chem.sEur. J. 2006, 12, 7254–7263.
(7) Loudet, A.; Bandichhor, R.; Burgess, K.; Palma, A.; McDonell, S. O.;
Hall, M. J.; O’Shea, D. F. Org. Lett. 2008, 10, 4771–4774.
Org. Lett., Vol. 13, No. 1, 2011
23

the classical procedure.4 Unfortunately, all attempts to
optimize the critical cyclization stepsschanging the solvent,
temperature, ammonium sources - failed and the yield
remained rather low, particularly for iodo derivatives 4c,d
mostly due to their poor solubility. Crystals suitable for X-ray
diffraction analysis were obtained for 4a and boron contain-
ing analogous 5a-c (Supporting Information and Scheme
1). The molecular structures are similar to that of already
described aza-Boron-dipyromethene dyes.8 5a-c exhibit a
strong intramolecular interaction between the two fluorine
atoms of the BF2 moiety and the ortho-protons from the
phenyl in 3/5 positions (Scheme 1), with average distances
of 2.737, 2.432, and 2.767 Å, respectively. Considering the
global yields, the bromo-functionalized intermediates 4a,b
were picked up to achieve the synthesis leading to the
formation of 6a,b with 86 and 73% yield, respectively.
Finally, the BF2 moiety was introduced classically using
boron trifluoride etherate and diisopropylethylamine.
All compounds were fully characterized by 1H, 13C NMR
spectroscopy, high resolution mass spectroscopy or elemen-
tary analyses (see Supporting Information). All NMR signals
(protons and carbons) of 7a,b were assigned by 2D NMR
experiments. Interestingly, the 13C{1H} JMOD NMR signal
assigned to the two ortho-carbon atoms belonging to the
phenyl in 3/5 positions appears as a well resolved triplet
(Figure 2). Such multiplicity is not observed in the dipy-
The spectroscopic properties were determined in diluted
dichloromethane solutions and are compiled in table 1.
Table 1. Spectroscopic Data in Dichloromethane Solution
λabs
λtheo
λem
ε
τ
abs
dye
nm
nm
nm
L mol-1 cm-1
ns
Φa
C
687
658
655
663
694
675
-
-
-
-
671
721
687
682
692
741
711
87 000
90 000
84 000
76 000
100 000
86 000
-
0.28
0.15
0.12
0.21
0.36
0.13
5a
5b
5c
7a
7b
-
-
-
2.70
1.55
665
a C as reference (CHCl3, Φ ) 0.36).4
Halogen substituted compounds 5a-c show the typical
behavior of aza-Boron-dipyromethene dyes with an intense
sharp absorption centered around 660 nm and a mirror
emission around 685 nm (Figure 3). Lengthening the
Figure 3. Absorption (top) and normalized emission (bottom) for
5a (black) and 5b (blue),7b (green) and 7a (red) in DCM. (Inset)
Deconvolution of 7b (green) in two Gaussian curves. Calculated
transitions for 7′a,b are given by vertical lines.
Figure 2.
JMOD 13C NMR (125.75 MHz, CDCl3) of 7b.
romethene precursors (6a,b) and is due to a through space
(TS) intramolecular coupling with the two fluorine atoms
with a JTSC-F coupling constant of about 4.6 and 4.1 Hz for
7a,b, respectively. This peculiar effect has been already
reported,9 and confirms that the H···F interactions observed
in the solid already occurs in solution.
conjugated skeleton (7a,b) results in a significant bathochro-
mic shift both in absorption (694 and 675 nm) and emission
(741 and 711 nm, respectively). The quantum yields of all
compounds were determined using Stern-Volmer plot
method using C as reference. They are rather modest except
for 7a. Absorption and emission are more red-shifted for a
24
Org. Lett., Vol. 13, No. 1, 2011

substitution in the 3/5 (7a) than in the 1/7 positions (7b).
This effect is also observed for the dipyromethene precursors
(6a,b) and can be therefore related to the dye structure itself:
the ortho-pyrollic position inducing a better delocalization.
In addition, 7a exhibits both quantum yield twice higher and
lifetime twice longer than 7b. These phenomena can be
rationalized by the rigidification induced by the C-H···F
interactions of the extended π-conjugated substitution in the
3/5 positions occurring for 7a, restricting free rotation
motions hence, nonradiative deactivation processes. When
compared to the benchmark C, 7a presents a larger quantum
yield efficiency (0.36 against 0.28 in DCM) and its emission
is more displaced into the NIR (740 nm against 720 nm).
This red-shift observed for 7a is mainly due to the longer
π-conjugated skeleton whose excited state reorganization
induces a larger Stokes shift (914 vs 686 cm-1 for C).
Finally, the nature of the transitions at the origin of the
absorption spectra was investigated by a time-dependent
density functional theory (see Supporting Information) in the
case of 7′a,b featuring methyl pendant group for simplicity
(Table 1). The calculated trends are in good agreement with
experimental data; in particular, the more pronounced red-
shift for the isomer substituted in the 3/5 positions (7′a) is
well reproduced.
HOMO-2 orbital is mainly developed over the periphery of
the molecule, delocalized from the phenyl to the fluorenyl
moieties suggesting that the second excitation presents a
pronounced charge-transfer (CT) character. Consequently,
the lowest energy transition can be best described as a mixing
of strong cyanine and minor charge transfer type transitions,
as already mentioned for Boron-dipyromethene dyes.10 This
admixing contributes to the red-shift of the spectroscopic
properties. In addition, the HOMO-1 f LUMO excitation,
featuring also a marked CT character (Figure 4) was
calculated at 547 and 584 nm for 7′a,b, respectively and
cannot be unambiguously attributed to an experimental band.
It may correspond either to the second band experimentally
observed at 490 and 524 nm for 7a,b, respectively or to the
shoulder observed in the lower energy transition (Figure 4,
inset), generally assigned to a vibronic contribution.10
Importantly, for both CT transitions, the nitro groups do
not behave as an acceptor (no contribution to the LUMO),
underlining the stronger electro-withdrawing character of the
central aza-Boron-dipyromethene moieties.
In conclusion, this paper describes an alternative way to
move the photophysical properties of aza-Boron-dipy-
romethene dyes to the NIR thanks to peripheral substitutions.
The extension of conjugation introduces some charge transfer
contribution in the lowest energy transitions and results in a
larger emission Stokes-shift due to excited state reorganiza-
tion. Both effects are responsible for the red-shift of the
spectroscopic properties. This study also pointed out the more
efficient 3/5 substitution in terms of delocalization and higher
rigidification due to the presence of intramolecular C-H···F
interactions.
In both cases, the lower energy transition is composed of
a major contribution of the HOMO f LUMO excitation and
a minor HOMO-2 f LUMO one (see Supporting Informa-
tion). The corresponding molecular orbitals are represented
in Figure 4 in the case of 7′a. The HOMO is mainly
Acknowledgment. We thank the Direction Ge´ne´rale de
l’Armement for a grant to Q.B. and funding support from
Thale`s. M. Lindgren from NTNU in Trondheim is acknowl-
edged for lifetime measurements. B.L.G. thanks the Poˆle
Scientifique de Mode´lisation Nume´rique (PSMN) at ENS
Lyon for computing facilities.
Supporting Information Available: Experimental pro-
cedures, characterization data, X-ray structures, crystal data,
and computational details. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL102701V
(8) (a) Killoran, J.; McDonnell, S. O.; Gallagher, J. F.; O’Shea, D. F.
New J. Chem. 2008, 32, 483–489. (b) Loudet, A.; Bandichhor, R.; Wu, L.;
Burgess, K. Tetrahedron 2008, 64, 3642–3654. (c) Bouit, P.-A.; Kamada,
K.; Feneyrou, P.; Berginc, G.; Toupet, L.; Maury, O.; Andraud, C. AdV.
Mater. 2009, 21, 1151–1154.
Figure 4. Orbitals mainly involved in the calculated excited states
of 7′a.
(9) (a) Chen, J.; Reibenspies, J.; Derecskei-Kovacs, A.; Burgess, K.
Chem. Commun. 1999, 2501–2502. (b) Xie, X.; Yuan, Y.; Kru¨ger, R.;
Bro¨ring, M. Magn. Reson. Chem. 2009, 47, 1024–1030.
distributed over the phenyls and alkynes and the central
pyrroles whereas the LUMO is centered on the central aza-
Boron-dipyromethene core. This monoelectronic excitation
presents a marked cyanine character. On the other hand, the
(10) Yu, Y.-H.; Descalzo, A. B.; Shen, Z.; Ro¨hr, H.; Liu, Q.; Wang,
Y.-W.; Spieles, M.; Li, Y.-Z.; Rurack, K.; You, X.-Z. Chem. Asian J. 2006,
1-2, 176–187.
Org. Lett., Vol. 13, No. 1, 2011
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