Benzimidazole-embedded N-fused aza-indacenes: Synthesis and deprotonation-assisted optical detection of carbon dioxide

Article abstract of DOI:10.1039/c3cc43938k

N-fused aza-indacene-based fluorophores 1 and 2 were prepared via a three-component condensation involving benzimidazole-carbinol, trifluoroacetic acid, and either pyrrole or indole, respectively. The N-fused aza-indacenes act as optical-based chemosensors for dissolved carbon dioxide gas following fluoride anion-mediated deprotonation.

Full text of DOI:10.1039/c3cc43938k

ChemComm
View Article Online
View Journal | View Issue
COMMUNICATION
Benzimidazole-embedded N-fused aza-indacenes:
synthesis and deprotonation-assisted optical detection
of carbon dioxide†
Masatoshi Ishida,ab Pyosang Kim,a Jiyoung Choi,c Juyoung Yoon,*c Dongho Kim*a
and Jonathan L. Sessler*ad
Cite this: Chem. Commun., 2013,
49, 6950
Received 25th May 2013,
Accepted 20th June 2013
DOI: 10.1039/c3cc43938k
www.rsc.org/chemcomm
N-fused aza-indacene-based fluorophores 1 and 2 were prepared via a fluoride anion-promoted deprotonation of the free NH pyrrolic proton.
three-component condensation involving benzimidazole-carbinol, tri- These dyes, which can be viewed as rigidified dipyrrins,6 are highly
fluoroacetic acid, and either pyrrole or indole, respectively. The N-fused fluorescent and display long-lived excited state lifetimes (up to 24 ns).
aza-indacenes act as optical-based chemosensors for dissolved carbon
dioxide gas following fluoride anion-mediated deprotonation.
Compound 1 was prepared by a conventional acid-condensation
reaction that involves treating carbinol (3) in dry MeCN with excess
pyrrole and trifluoroacetic acid (TFA) (Fig. 1). Subjecting the mixture to
Detection and monitoring of dissolved carbon dioxide (CO2) is of reflux for 48 h, followed by treatment with 2,3-dichloro-5,6-dicyano-p-
fundamental importance in a diverse array of applications ranging benzoquinone (DDQ), afforded a black tarry residue. A preliminary
from medical diagnosis to environmental monitoring.1 Not surpris- thin-layer chromatographic (TLC) analysis of this residue revealed the
ingly, therefore, the development of novel optical-based CO2 sensing presence of a highly luminescent fraction. This fraction, which proved
systems has attracted considerable interest lately with a key goal being to be compound 1, was then isolated by column chromatography over
to establish simple, inexpensive and rapid sensing capabilities.2 Never- silica gel and recrystallized from CHCl3–hexane to give yellow crystals
theless, CO2 detection remains challenging, in part because carbon of 1 in 2% yield.
dioxide is a relatively inert (weak electrophile) and colourless gas.
An X-ray crystal structure of 1 revealed an unexpected benzo[4,5]-
Recently, we reported an optical sensor system3 for CO2 that relies on imidazo[1,2-a]pyridine-containing aza-indacene-like structure, wherein
the reaction of CO2 with an N-heterocyclic carbene (NHC) generated an annulated central six-membered ring with a trifluoromethyl methine
in situ from the corresponding benzobisimidalium cation. However, the bridge is present (Fig. 2a and b). The core is nearly planar with a mean
NHCs employed are not strong chromophores. This finding has led us plane deviation of 0.064 Å. This finding is consistent with a high degree
to consider that highly nucleophilic nitrogen centers constrained within of p-conjugation, a feature that is further reflected in the individual
a dye system might act as improved CO2 sensors. Such species would bond lengths seen within 1 (Fig. S2 in ESI†). Analysis of the crystal
be expected to form an N–CO2 adduct via repolarization of the packing diagram reveals a one-dimensional (1D) supramolecular
OQCQO bonds.4 In appropriate systems, this transformation would
give rise to changes in the optical features, thus permitting CO2
sensing.5 In an effort to test this possibility, we have synthesized the
N-fused aza-indacene analogues 1 and 2. As detailed below, these
systems act as colorimetric and fluorescence-based CO2 sensors upon
a Department of Chemistry, Yonsei University, Shinchon-dong 134, Seodaemun-gu,
Seoul, 120-749, Korea. E-mail: dongho@yonsei.ac.kr; Fax: +82-2-2123-2434
b Education Center for Global Leaders in Molecular Systems for Devices,
Kyushu University, Fukuoka 819-0395, Japan
c Department of Chemistry and Nano Science and Department of Bioinspired
Science, Ewha Womans University, Seoul 120-750, Korea.
E-mail: jyoon@ewha.ac.kr
d Department of Chemistry & Biochemistry, University of Texas at Austin,
105 E. 24th Street - Stop A5300, Austin, Texas 78712-1224, USA.
E-mail: sessler@cm.utexas.edu; Fax: +1 512-471-5009
Fig. 1 Synthesis of 1 and 2 and their subsequent reactions with CX2 (X = O or S).
Note: EDC was only used in the case of indole. The photographs show the products
obtained after reaction with tetrabutylammonium fluoride (TBAF) (lower set) and
after either subsequent reaction with CO2 or prior to any reaction (top set). Photos
taken under ambient light (left) or using a UV-lamp (right, lex = 365 nm).
† Electronic supplementary information (ESI) available: Details of experimental
procedures, syntheses, crystallographic data for 1 and 2 and supporting figures
and tables. CCDC 940145 and 940146. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c3cc43938k
c
6950 Chem. Commun., 2013, 49, 6950--6952
This journal is The Royal Society of Chemistry 2013

View Article Online
Communication
ChemComm
method were found to be 19.35 and 23.95 ns, respectively. These
lifetimes are considerably longer than those of typical organic
fluorophores (e.g., BODIPY: B7 ns, pyrrolopyrrole cyanine: B4 ns,
fluorescein: B4 ns) (Fig. S6, ESI†).8 The nonradiative (knr) decay rate
constants were estimated to be 6.2 Â 106 sÀ1 and 1.2 Â 107 sÀ1 for 1
and 2, respectively. The photophysical behavior of 1 and 2 was found
to be largely independent of the choice of solvent, as expected for
rigid systems that are likely to suppress nonradiative decay path-
ways. It is thus consistent with the relatively small Stokes shifts seen
for these two systems. The electronic structures of 1 and 2, as
inferred from B3LYP/6-31G(d,p) level calculations, proved similar to
those of the BODIPY dyes (Fig. S8, ESI†) in that both the HOMOs
and LUMOs of 1 and 2 are delocalized over the whole core structure,
with only a small contribution from the meso-phenyl rings. The
simulated stick spectra of 1 and 2 obtained from time dependent
(TD) DFT calculations are consistent with the experimental absorp-
tion spectra (Fig. S9, ESI†).
Fig. 2 Single crystal X-ray diffraction structures of 1 and 2 (thermal ellipsoids at
50% probability). Solvent molecules are omitted for clarity; (a) and (c) front views;
(b) and (d) side views of 1 and 2, respectively.
To investigate whether the deprotonated form of 2 reacts
structure, wherein individual units of 1 are aligned along the b-axis of with CO2 gas to produce an observable optical response, we first
the crystal lattice. This arrangement is stabilized in the solid state by a evaluated whether this aza-indacene and its congener 1 could
combination of Npyrrole–HÁÁÁNimidazole intermolecular hydrogen bonding be readily deprotonated by a fluoride anion.9 Upon addition of
interactions, as well as p–p interactions between the benzimidazole unit n-tetrabutylammonium fluoride (TBAF) to an acetonitrile
and the meso-phenyl ring (Fig. S3, ESI†). Support for these proposed (MeCN) solution of 2, the broad absorption band in the visible
interactions comes from Hirschfield surface plots and fingerprint region characteristic of 2 was found to diminish, with a large
analyses (Fig. S3, ESI†).
bathochromic shift in the band (lmax = 620 nm) (Fig. S10a,
The high resolution mass spectrum (HR-MS) and 1H-NMR ESI†). A 1 : 1 transformation from the neutral form of 2 to the
spectrum (CD2Cl2) were consistent with the structure proposed for deprotonated species (referred to as 2-F) via proton transfer was
1 (ESI†). A singlet was also observed at À53.19 ppm in the 19F-NMR inferred based on the observation of clear isosbestic points, as
spectrum that is assigned to the trifluoromethyl group.
well as clean Job’s plot behavior (Fig. S11, ESI†). The corres-
It is proposed that formation of 1 involves a set of domino-type ponding equilibrium constant was determined to be 8.3 Â
reactions, wherein TFA reacts to form an amide bond, followed by 104 MÀ1 by a nonlinear least-square fitting analysis. In the case
1
electrophilic aromatic substitution and a dehydrative annulation of the pyrrole analogue, 1, a H-NMR spectral titration10 with
(Scheme S1, ESI†). TFA thus plays a role as a building block to TBAF was carried out in CD2Cl2; this revealed the disappear-
construct the central pyridine ring, and as an acid catalyst for the ance of the pyrrole NH signal at 8.4 ppm (Fig. S13, ESI†).11
condensation between the heterocyclic subunits.
Along with the absorption spectral changes, the fluorescence of 2
The reaction of 3 with indole in the presence of trifluoroacetic was found to be quenched upon the addition of TBAF (Fig. S9b,
acid and EDC (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide ESI†).12 This deprotonation event appears specific to FÀ, and is
hydrochloride) also resulted in formation of a TFA-fused derivative thought to reflect the distinct electronegativity of the fluoride anioÀn.
(2) in 4% yield (Fig. 1).7 Again, spectral data consistent with the Upon addition of other anions, such as ClÀ, BrÀ, IÀ, ClO4À, NO3
,
proposed structure were obtained (ESI†). A single crystal X-ray AcOÀ, HSO4À, H2PO4À as the corresponding TBA salts in MeCN, no
structural analysis of 2 revealed a similar annulated core structure spectral response was seen (Fig. S10c and d, ESI†).
and an analogous 1D-linear supramolecular packing arrangement
When the MeCN solution of 2-F formed from 2 by pre-treatment
(Fig. 2c and d and Fig. S3 and S4, ESI†). Compared to 1, a higher with TBAF (4 equiv.), was exposed to CO2 gas via bubbling, both the
level of distortion was seen in 2 (mean plane deviation = 0.087 Å). absorption and emission spectra of 2-F were found to change
Presumably, this reflects steric repulsion between the CF3 group and dramatically (Fig. 3). Based on the specific optical changes observed,
the aromatic o-CHs subunits of the flanking rings (Fig. S5, ESI†).
this exposure was thought to lead to recovery of the original species 2.
1
As expected for relatively rigid chromophores, the N-fused aza- Support for this conclusion came from H-NMR spectral analysis of
indacenes 1 and 2 both displayed well-defined photophysical proper- the CD3CN solution of 2-F obtained after treatment with CO2 gas; the
ties (Fig. S6, S7 and Table S1, ESI†). The UV/vis absorption spectra resulting spectrum proved coincident with that for 2 (Fig. S14, ESI†).
recorded in CH2Cl2 revealed an intense band at 277 nm (e = 5.8 Â
The selectivity of anionic 2 for CO2 is remarkably high, with
104 MÀ1 cmÀ1) and broad bands at 315, 360, 464 and 468 nm for 1, no interference being produced in the presence of atmospheric
and strong bands at 289 (e = 5.6 Â 104 MÀ1 cmÀ1) and 313 (e = 7.1 Â gasses, such as nitrogen, oxygen or argon. The fluorescence of 2
104 MÀ1 cmÀ1), as well as features at 459 and 482 nm, for 2. was regenerated after bubbling approximately 1.3 mL of CO2 gas
Moreover, 1 and 2 showed strong fluorescence signals centered at per 2 mL of a solution (Fig. 3b). For a 10 mM solution of 2-F in
493 and 522 nm, respectively, that were characterized by high CD3CN, 50% conversion was observed when the concentration of
fluorescence quantum yields (FF = 0.88 and 0.71, respectively). The CO2 was approximately 1.0 mM (as deduced from gas solubility
fluorescence lifetimes (tfl) of 1 and 2 determined by the TCSPC data13). The detection limit for CO2 under these conditions was
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 6950--6952 6951

View Article Online
ChemComm
Communication
This work was supported by the U.S. National Science
Foundation (grant CHE-1057904), the Robert A. Welch Foundation
(F-1018), the World Class University program (R32-2012-000-10217-0)
of the National Research Foundation of Korea funded by the
Ministry of Education, Science and Technology, and a Korean
National Creative Research Initiative (2012R1A3A2048814). The
authors thank Dr V. Lynch (The University of Texas) for help with
the crystallographic analysis.
Fig. 3 (a) UV-vis absorption and (b) fluorescent spectra of 2 (black; 1.0 Â 10À5 M)
recorded in acetonitrile (MeCN) in the presence of tetrabutylammonium fluoride
(TBAF) (4.0 Â 10À5 M) followed by bubbling with different volumes of CO2
(red); lex = 410 nm at 298 K. The inset in (b) shows a plot of the fluorescent
intensity I522nm of a solution containing 2 and 4.0 equiv. of TBAF versus CO2 volume
(lex = 410 nm).
Notes and references
´
1 (a) G. Jimenez-Cadena, J. Riu and F. X. Rius, Analyst, 2007, 132, 1083;
(b) C. E. W. Hahn, Analyst, 1998, 123, 57R; (c) M. C. Frost and
M. E. Meyerhoff, Curr. Opin. Chem. Biol., 2002, 6, 633;
(d) K. S. Johnson, J. A. Needoba, S. C. Riser and W. J. Showers,
Chem. Rev., 2007, 107, 623.
thus calculated to be 4.1 Â 10À7 M (Fig. S15, ESI†). Moreover,
even without bubbling, i.e., simply exposing a solution of 2-F to a
1 atm blanket of CO2 gas gives rise to spectral changes within
reasonable time scales (Fig. S16a, ESI†). ON–OFF cycling between
neutral 2 and deprotonated 2-F could be could be carried out
multiple times without appreciable degradation (Fig. S16b, ESI†).
While not detected directly, we invoke the CO2-adduct, 2-
CO2, as an intermediate species in the sensing process (Fig. 1).
Many conventional CO2-sensing processes are sensitive to
water, and it has been reported that bicarbonate (HCO3À) iÀs
involved in the underlying reactions.5 In our case, the HCO3
anion, produced by the presumed hydrolysis of 2-CO2, was
identified via 13C-NMR spectral analysis with a characteristic
singlet being observed at 159.1 ppm (Fig. S17a, ESI†).12
Carbon disulfide is an isoelectronic analogue of CO2, wherein
the sulfur atoms can accept negative charge from the attacking
nucleophilic pyrrolic anion. This is expected to provide effective
stabilization of the resulting adduct. Therefore, the reactivity of 2-F
toward CS2 was also investigated. This control study produced the
bithiocarbonate anions (HOCS2À) as evidenced from a 13C-NMR
signal at À236.6 ppm; it also led to recovery of the fluorescent
spectral features characteristic of 2 (Fig. S17b, ESI†).14
As a further control study, the reference molecule, di-t-butyl-
substituted carbazole (5) was used to prepare the corres-
ponding N-dithiolate derivative (5-CS2). This was done by
subjecting 5 to treatment with NaH followed by reaction with
CS2 in DMSO solution. The product was characterized via NMR
spectral analysis and found to be stable on the laboratory time
scale (Fig. S18, ESI†). The difference in the chemical stability of
the N-dithiolate adducts formed from 2 and 5 is ascribed
primarily to differences in steric hindrance. The neighboring
meso-phenyl group in 2 is expected to weaken the N-C(S2) bond,
thus allowing release of the bithiocarbonate anion (as well as
presumably the bicarbonate anion in the case of CO2).4
2 (a) X. Xie, M. Pawlak, M. Tercier-Waeber and E. Bakker, Anal. Chem.,
2012, 84, 3163; (b) R. Ali, T. Lang, S. M. Saler, R. J. Meier and
O. S. Wolfbeis, Anal. Chem., 2011, 83, 2846; (c) Y. Liu, Y. Tang,
N. N. Barashkov, I. S. Irgibaeva, J. W. Y. Lam, R. Hu,
D. Birimzhanova, Y. Yu and B. Z. Tang, J. Am. Chem. Soc., 2010,
132, 13951; (d) D. Wencel, J. P. Moore, N. Stevernson and
C. McDonagh, Anal. Bioanal. Chem., 2010, 398, 1899.
3 Z. Guo, N. R. Song, J. H. Moon, M. Kim, E. J. Jun, J. Choi, J. Y. Lee,
C. W. Bielaski, J. L. Sessler and J. Yoon, J. Am. Chem. Soc., 2012,
134, 17846.
4 V. B. Kobychev, N. M. Vitkovskaya, I. L. Zaytseva, E. Y. Larionova and
B. A. Trofimov, Int. J. Quantum Chem., 2002, 88, 542.
5 (a) I. Ravikumar and P. Ghosh, Chem. Commun., 2010, 46, 1082;
(b) S. J. Brooks, P. A. Gale and M. E. Light, Chem. Commun., 2006,
4344; (c) T. Gunnlaugsson, P. E. Kruger, P. Jensen, F. M. Pfeffer and
G. M. Hussey, Tetrahedron Lett., 2003, 44, 8909; (d) M. Boiocchi,
´
L. D. Boca, D. E. Gomez, L. Fabbrizzi, M. Licchelli and E. Monzani,
J. Am. Chem. Soc., 2004, 126, 16507.
6 (a) T. E. Wood and A. Thompson, Chem. Rev., 2007, 107, 1831;
(b) D. T. Gryko, D. Gryko and C.-H. Lee, Chem. Soc. Rev., 2012,
41, 3780.
7 The relatively high electron density at the C-2 position as reflected
in the HOMOs of pyrrole and indole, respectively, could account for
the greater degree of electrophilic substitution that is proposed to
take place at C-2 as compared to C-3 (Scheme S1, ESI†).
8 H. L. Kee, C. Kirmaier, L. Yu, P. Thamyongkit, W. J. Youngbood,
M. E. Calder, L. Ramos, B. C. Noll, D. F. Bocian, W. R. Scheidt,
R. R. Birge, J. S. Lindsey and D. Holten, J. Phys. Chem. B, 2005,
109, 20433; M. Y. Berezin, W. J. Akers, K. Guo, G. M. Fischer,
E. Daltrozzo, A. Zumbusch and S. Achilefu, Biophys. J., 2009, 97, L22;
M. Hammer, D. Schweitzer, S. Richter and E. Konigsdorffer, Physiol.
Meas., 2005, 26, N9.
9 For examples of fluoride anion sensing systems that involve depro-
tonation, see: (a) Y. Qu, J. Hua and H. Tian, Org. Lett., 2010, 12, 3320;
(b) L. E. Santos-Figueroa, M. E. Moragues, M. M. M. Raposo,
´
R. M. F. Batista, S. P. G. Costa, R. C. M. Ferreira, F. Sancenon,
´
´˜
R. Martınez-Manez, J. V. Ros-Lisa and J. Soto, Org. Biomol. Chem.,
2012, 10, 7418; (c) T. H. Kim, M. S. Choi, B.-H. Sohn, S.-Y. Park,
W. S. Lyoo and T. S. Lee, Chem. Commun., 2008, 2364;
(d) V. Amendola and L. Fabbrizzi, Chem. Commun., 2009, 513;
(e) C. Caltagirone, A. Mulas, F. Isaia, V. Lippolis, P. A. Gale and
M. A. Light, Chem. Commun., 2009, 6279.
10 A spectral response analogous to that for 2 was seen when 1 was treated
with the fluoride anion. The corresponding equilibrium constant was
3.4 Â 105 MÀ1 in MeCN solution (cf. Fig. S11 and S12, ESI†).
11 An 1H NMR spectral titration involving 2 and TBAF could not be
carried out due to the low solubility of 2 in common organic
solvents.
In summary, we have synthesized two novel p-extended
N-fused aza-indacene analogues, namely 1 and 2. The restricted
p-conjugated structures of 1 and 2 are thought to account 12 Upon excitation at the lowest absorption band (lex = 620 nm), a near
IR emission feature was observed at lmax = 681 nm (FF B 0.01) for
the deprotonated form of 2; see ESI†.
13 A. Gennaro, A. A. Isse and E. Vianello, J. Electroanal. Chem., 1990,
for their highly emissive behavior and their uncommonly long
lifetimes (tfl B 24 ns). Taking advantage of these optical features,
as well as the ON–OFF switching capabilities afforded by
deprotonation, the derivative 2 was demonstrated as providing
a convenient and easy-to-visualize chemosensing system for the
detection of dissolved CO2.
289, 203.
14 A 13C NMR chemical shift of d = 233.6 ppm for CH3OCS2À has been
À
reported in D2O. see; D. Stueber, D. Patterson, C. L. Mayne,
A. M. Orendt, D. M. Grant and R. W. Parry, Inorg. Chem., 2001,
40, 1902.
c
6952 Chem. Commun., 2013, 49, 6950--6952
This journal is The Royal Society of Chemistry 2013