L-shaped benzimidazole fluorophores: Synthesis, characterization and optical response to bases, acids and anions

Article abstract of DOI:10.1039/c2cc37120k

Nine L-shaped benzimidazole fluorophores have been synthesized, computationally evaluated and spectroscopically characterized. These "half-cruciform" fluorophores respond to bases, acids and anions through changes in fluorescence that vary from moderate t

Full text of DOI:10.1039/c2cc37120k

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L-shaped benzimidazole fluorophores: synthesis,
characterization and optical response to bases, acids
and anions†‡
Cite this: Chem. Commun., 2013,
49, 4304
Received 30th September 2012,
Accepted 17th October 2012
ˇ
´
Rio Carlo Lirag,y Ha T. M. Ley and Ognjen S. Miljanic*
DOI: 10.1039/c2cc37120k
www.rsc.org/chemcomm
Nine L-shaped benzimidazole fluorophores have been synthesized,
computationally evaluated and spectroscopically characterized. These
‘‘half-cruciform’’ fluorophores respond to bases, acids and anions
through changes in fluorescence that vary from moderate to dramatic.
Molecular cruciforms1—cross-conjugated molecules in which two
conjugation circuits intersect at a central core—have been promi-
nently used as fluorescent sensors for carboxylic2 and boronic acids,2b
amines,3 metal ions,1,4 small organic and inorganic anions3a,5 and
phenols.2b With appropriate substitution, cruciforms localize their
HOMO and LUMO orbitals on different ‘‘arms’’ of the molecule; this
spatial separation of frontier molecular orbitals (FMOs) is essential to
the use of cruciforms as sensors, since analyte binding to the
cruciform invariably affects its HOMO–LUMO gap and the associated
optical properties. Our group was particularly focused on the
synthesis and study of cruciforms based on the benzobisoxazole
nucleus.6 In this communication, we introduce a new class of
L-shaped fluorophores based on the related benzimidazole7 nucleus.
Formally, these systems represent ‘‘cruciforms cut in half’’, and this
structural simplification permits us to explore minimal systems
which preserve spatially isolated FMOs. At the same time, the dual
acidic–basic nature of the benzimidazole nucleus could potentially
allow the use of this sensing motif in the direct identification and
quantification of both acidic and basic analytes.
Scheme 1 Synthesis of fluorophores 5–13.
Benzimidazole fluorophores 5–13 were synthesized (Scheme 1)
in two steps starting from 3-bromo-o-phenylenediamine (1).8
Its oxidative condensation9 with three commercially available
aldehydes produced brominated imidazoles 2–4, which were
subjected to Sonogashira couplings with either phenylacetylene,
4-ethynylpyridine, or 4-ethynyl-N,N-dimethylaniline, to generate
the final desired products in moderate yields. Fluorophores 5–13
were isolated as off-white, yellow or light green powders, following
chromatography and/or recrystallization. In the case of donor–
acceptor systems 10 (Fig. 1, right) and 12 (not shown), their
University of Houston, Department of Chemistry, 136 Fleming Building, Houston,
TX 77204-5003, USA. E-mail: miljanic@uh.edu; Fax: +1 (713)743-2709;
Tel: +1 (832)842-8827
† This article is part of the ChemComm ‘Emerging Investigators 2013’ themed
issue.
‡ Electronic supplementary information (ESI) available: Synthesis and full char-
acterization data for all new compounds, detailed orbital diagrams for all
synthesized compounds, plots of UV/Vis absorption and fluorescence spectral
changes during acid and base titrations. See DOI: 10.1039/c2cc37120k
§ These authors contributed equally to this work.
Fig. 1 Emission colours of benzimidazoles 5 (left) and 10 (right) in five different
solvents (CH = cyclohexane, DCM = dichloromethane, THF = tetrahydrofuran).
Excitation was achieved using a handheld UV lamp, lexc = 365 nm.
c
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Fig. 2 Frontier molecular orbitals of L-shaped benzimidazole fluorophores 5 (left)
and 10 (right). Only one of the two possible tautomers was considered (see ESI‡
for the FMOs of the other tautomers, as well as other L-shaped fluorophores).
fluorescence emission is highly solvent-dependent; on the other
extreme, the very weak fluorescence of ‘‘neutral’’ diphenyl substi-
tuted compound 5 is independent of the solvent (Fig. 1, left). It
should also be noted that the NMR spectra of 5–13 are often more
complex than structures in Scheme 1 would suggest (see ESI‡ for
details), because of the N–H tautomerization between the imida-
zole’s two nitrogen atoms.
Computational insight into the FMOs of 5–13 was obtained using
Gaussian 09W10 software package and its accompanying graphical
interface program GaussView 5.0, at the B3LYP/6-31G++ level of
theory. Fig. 2 shows the HOMO and LUMO orbitals of two extreme
cases: diphenyl substituted compound 5 and the donor–acceptor
system 10 (see ESI‡ for FMOs of all other L-shaped fluorophores). In
these two compounds, trends previously observed for benzobisox-
azole6a (and other) cruciforms are again borne out. Both the HOMO
and the LUMO of compound 5 are significantly delocalized across
the molecule. In contrast, 10 shows considerably localized FMOs:
most of the LUMO density is placed along the pyridine-bearing arm
of the half-cruciform, while most of the HOMO density resides along
the electron-rich dimethylaniline-group. In both compounds,
HOMO is the more localized of the two FMOs.
Fig. 3 UV/Vis absorption (top) and emission (bottom) spectra for the titrations
of THF solutions of fluorophores 5 (left two spectra) and 10 (right two spectra)
with a concentrated aqueous solution of TBA+OHÀ. Excitation wavelengths for
fluorescence emission titrations of 5 and 10 were 337 and 378 nm, respectively.
Compounds 5 and 10 will be the chief subjects of discussion in
this communication, as they allowed us to separate the effects of the
benzimidazole nucleus alone (in 5) from those introduced by the
donor–acceptor substitution and the resultant FMO spatial isolation
(in 10). Analogous experiments for all other benzimidazole fluoro-
phores are described in ESI.‡ In light of the spatially separated
FMOs in 10, its solvatochromicity can be rationalized by the
apparent charge separation in the excited state.
Fig. 4 UV/Vis absorption (top) and emission (bottom) spectra for the titrations
of THF solutions of fluorophores 5 (left two spectra) and 10 (right two spectra)
with a concentrated solution of TFA in THF. Excitation wavelengths for fluores-
cence emission titrations of 5 and 10 were 313 and 362 nm, respectively.
Our next set of experiments focused on the titration of the
solutions of the prepared benzimidazole fluorophores with a
concentrated aqueous solution of tetrabutylammonium hydroxide and slight attenuation of its emission (Fig. 4, bottom left; +47 nm).
(TBA+OHÀ). In both fluorophores, red shifts in absorption (Fig. 3, Since this compound can be protonated only at benzimidazole, it
top; +45 nm for 5 and +18 nm for 10) and emission (Fig. 3, bottom; would follow that this protonation preferentially stabilizes the
+54 nm for 5 and +43 nm for 10) were observed, with clear LUMO. Compound 10, on the other hand, responds by a red shift
isosbestic points suggesting simple interconversion between just in absorption (Fig. 4, top right; +29 nm) and a blue shift and
two species: compounds 5 and 10 and their conjugate bases significant attenuation of its emission (Fig. 4, bottom right;
deprotonated at the benzimidazole (pKa E 12.8).11 These red À35 nm). In 10, there are three possible protonation sites: dimethyl-
shifts indicate that deprotonation destabilizes HOMO more than aniline, pyridine and imidazole, with quite similar pKa values for
the LUMO; the largely analogous responses of 5 and 10 are a their conjugated acids of 5.15, 5.25 and 5.53, successively.11,12 The
consequence of the fact that both FMOs in both compounds have observed blue shift in the emission is consistent with the stabili-
significant densities along the imidazole N–H bond being cleaved. zation of HOMO, which would suggest that pyridine protonation is
Perhaps surprisingly, response of the prepared half-cruciform probably not operational, since HOMO has essentially no density on
sensors to acids was more difficult to rationalize. Both 5 and 10 are the pyridine nucleus. It is still unclear, however, which of the other
largely unresponsive to trifluoroacetic acid (TFA) until Àlog[TFA] of two sites is protonated first, and why absorption and emission
approx. 2.30 is reached. At this point, 5 shows a minimal blue shift maxima shift in the opposite directions. In order to obtain more
in absorption (Fig. 4, top left; À7 nm) and a much larger red shift predictable optical response to protonation—similar to those of our
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Fig. 5 Changes in the emission colour of benzimidazole sensors 5 (left) and 10
(right) upon exposure to anions. Anions were added in excess as their TBA+ salts.
Emission colours were recorded in THF, using a handheld UV lamp (lexc = 365 nm)
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cruciforms 5 and 10 can be used as fluorescent sensors for
small inorganic and organic anions.13 Dilute solutions of 5 and
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representative anions. Fig. 5 summarizes the emission colour
changes resulting from these additions. Both sensors minimally
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ClÀ, NO3À and ClO4À anions. However, more basic FÀ, AcOÀ and
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3À
PO4 anions turned ON the fluorescence of 5 and also signifi-
cantly modulated the emission colour of 10—particularly in the
case of fluoride.
In conclusion, benzimidazole fluorophores described here
can be easily synthesized in two steps. Their optical response
to acids is moderate and somewhat difficult to rationalize,
presumably on the account of (a) similar basicities of several
possible protonation sites, and (b) incomplete spatial separa-
tion of FMOs within the molecules. On the other hand, their
response to bases is much more dramatic, as all but two
members of this class consistently shift their emission maxima
toward the red region. The fact that these fluorophores preserve
their fluorescence upon deprotonation is intriguing, as it
suggests that benzimidazolate anions of 5–13 could potentially
be used as building blocks for the porous zeolitic imidazolate
frameworks (ZIFs),14 thus opening up routes to crystallographically
ordered solid-state sensors. We are exploring this and other
applications of the L-shaped benzimidazole fluorophores and will
report our findings in due course.
This research was generously supported by the National
Science Foundation CAREER program (CHE-1151292), the
Welch Foundation (grant no. E-1768), the University of Houston
(UH) and the Texas Center for Superconductivity at UH. Prof.
Thomas A. Albright and Mr Jaebum Lim (UH) are gratefully
acknowledged for assistance with computations and fluores-
cence titrations, respectively.
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12 These values are quoted for the parent molecules, and may in fact
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