Positive homotropic allosteric receptors for neutral guests: Annulated tetrathiafulvalene-calix[4]pyrroles as colorimetric chemosensors for nitroaromatic explosives

Article abstract of DOI:10.1002/chem.200902924

The study of positive homo- tropic allosterism in supramolecular receptors is important for elucidating design strategies that can lead to increased sensitivity in various molecular recognition applications. In this work, the cooperative relationship between tetrathiafulvalene (TTF)-calix[4]pyr- roles and several nitroaromatic guests is examined. The design and synthesis of new annulated TTF-calix[4]pyrrole receptors with the goal of rigidifying the system to accommodate better ni- troaromatic guests is outlined. These new derivatives, which display significant improvement in terms of binding constants, also display a positive homo- tropic allosteric relationship, as borne out from the sigmoidal nature of the binding isotherms and analysis by using the Hill equation, Adair equation, and Scatchard plots. The host-guest complexes themselves have been characterized by single-crystal X-ray diffraction analyses and studied by means of UV- spectroscopic titrations. Investigations into the electronic nature of the receptors were made by using cyclic voltam- metry; this revealed that the binding efficiency was not strictly related to the redox potential of the receptor. On the other hand, this work serves to illustrate how cooperative effects may be used to enhance the recognition ability of TTF-calix[4]pyrrole receptors. It has led to new allosteric systems that function as rudimentary colorimetric che- mosensors for common nitroaromatic- based explosives, and which are effective even in the presence of potentially interfering anions.

Full text of DOI:10.1002/chem.200902924

DOI: 10.1002/chem.200902924
Positive Homotropic Allosteric Receptors for Neutral Guests: Annulated
Tetrathiafulvalene–Calix[4]pyrroles as Colorimetric Chemosensors for
Nitroaromatic Explosives
Jung Su Park,[a] Franck Le Derf,[a] Christopher M. Bejger,[a] Vincent M. Lynch,[a]
Jonathan L. Sessler,*[a] Kent A. Nielsen,[b] Carsten Johnsen,[b] and Jan O. Jeppesen*[b]
Dedicated to Professor Jean-Marie Lehn on the occasion of his 70th birthday
Abstract: The study of positive homo-
tropic allosterism in supramolecular re-
ceptors is important for elucidating
design strategies that can lead to in-
creased sensitivity in various molecular
recognition applications. In this work,
the cooperative relationship between
constants, also display a positive homo-
tropic allosteric relationship, as borne
out from the sigmoidal nature of the
binding isotherms and analysis by using
the Hill equation, Adair equation, and
Scatchard plots. The host–guest com-
plexes themselves have been character-
ized by single-crystal X-ray diffraction
analyses and studied by means of UV-
spectroscopic titrations. Investigations
into the electronic nature of the recep-
tors were made by using cyclic voltam-
metry; this revealed that the binding
efficiency was not strictly related to the
redox potential of the receptor. On the
other hand, this work serves to illus-
trate how cooperative effects may be
used to enhance the recognition ability
of TTF-calix[4]pyrrole receptors. It has
led to new allosteric systems that func-
tion as rudimentary colorimetric che-
mosensors for common nitroaromatic-
based explosives, and which are effec-
tive even in the presence of potentially
interfering anions.
tetrathiafulvalene
(TTF)-calix[4]pyr-
roles and several nitroaromatic guests
is examined. The design and synthesis
of new annulated TTF-calix[4]pyrrole
receptors with the goal of rigidifying
the system to accommodate better ni-
troaromatic guests is outlined. These
new derivatives, which display signifi-
cant improvement in terms of binding
Keywords: allosterism · chemosen-
sors · cooperative effects · explo-
sives · supramolecular chemistry ·
tetrathiaACTHNUTRGENUGfN ulvalenes
Introduction
chemist.[1] Allosteric interactions, and the associated cooper-
ative reaction to initial binding events, are key features of
many biological processes; they provide, for instance, the
tight regulation of oxygen binding by hemoglobin[2] and un-
derlie the exquisite control observed in many enzymatic
processes.[3] Among the four distinctive categories of allos-
tery conceivable for synthetic receptors with multiple bind-
ing sites for a single substrate, namely 1) negative hetero-
tropic, 2) positive heterotropic, 3) negative homotropic, and
4) positive homotropic, only the latter provides an ampli-
fied, positive response to the initial binding of a given chem-
ical species. Unfortunately, simple systems capable of elicit-
ing this type of allosteric response are rare.[4] This is particu-
larly true in the case of neutral substrate recognition, and in
the specific case of nitroaromatic explosives detection[5] we
are unaware of any examples where the principles of coop-
erativity have been exploited to enhance the binding re-
sponse. Here, we report an extremely simple, yet effective,
in situ colorimetric sensing material (“chemosensor”) for ni-
The design and construction of new artificial receptors dis-
playing a positive homotropic allosteric response for target-
ed guests is a well-appreciated challenge for the biomimetic
[a] J. S. Park, Dr. F. Le Derf, C. M. Bejger, Dr. V. M. Lynch,
Prof. J. L. Sessler
Department of Chemistry and Biochemistry
The University of Texas at Austin
1 University Station, A5300, Austin, TX 78712 (USA)
Fax : (+1)512-471-7550
E-mail: sessler@mail.utexas.edu
[b] Dr. K. A. Nielsen, C. Johnsen, Prof. J. O. Jeppesen
Department of Physics and Chemistry
University of Southern Denmark
Campusvej 55, 5230 Odense M (Denmark)
E-mail: joj@ifk.sdu.dk
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200902924.
848
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FULL PAPER
troaromatic explosives that is based on the use of modified
tetrathiafulvalene (TTF)-calix[4]pyrrole frameworks.
positive homotropic allosterism in their binding with the test
polynitroaromatic explosives TNB, picric acid (TNP), and
2,4,6-trinitrotoluene (TNT). These cooperative effects are
correlated with a corresponding increase in colorimetric
sensing ability.
Prior to this work, we described the synthesis of the TTF-
functionalized calix[4]pyrrole 4 (Scheme 1).[6] This first-gen-
The design rationale for the present work was the realiza-
tion that the parent TTF-calix[4]pyrrole 4 could be modified
through annulation of an aromatic moiety onto the TTF
subunit. Specifically, we thought that this approach could be
exploited to enlarge and rigidify the “TTF walls”, thus,
making this class of electron-rich receptors a better match in
terms of size and shape for flat electron-deficient substrates,
such as TNB, TNP, and TNT. This annulation was also ex-
pected to reduce the flexibility of the system as a whole.
This, in turn, was considered likely to enhance the binding
of a second substrate in accord with the generalized mecha-
nistic postulate given in Scheme 2. On the other hand, it was
also appreciated that annulation with an aromatic moiety
would modulate both the nature of the p surface (size and
shape), as well as the electronic properties of the system
(e.g., redox potentials, donor ability, dipole moment orienta-
tion, etc.), in addition to providing flat p surfaces that are
extended relative to those present in 4. Depending on their
specific nature, such variations could serve to increase or de-
crease the propensity to form donor–acceptor complexes.
They could also affect the hydrogen bonding donor ability
of the pyrrolic NH protons. Thus, one goal of the present
study was to gain insight into the interplay of these poten-
tially competing factors with the hope of developing systems
that displayed an enhanced guest-dependent colorimetric re-
sponse for canonical nitroaromatic analytes represented by
our test substrates TNB, TNP, and TNT.
Scheme 1. Synthesis of the TTF-calix[4]pyrrole derivatives 4, 5, and 6.
eration system was found to undergo a fast, easy to visualize
color change (from yellow to green) when exposed to 1,3,5-
trinitrobenzene (TNB) in organic solvents in the absence of
chloride ion. However, receptor 4 is characterized by only
modest binding affinities towards TNB and was found to re-
quire relatively high concentrations to produce a naked eye
detectable colorimetric response (e.g., [TNB]ꢀ2 mm and
[4]=1 mm) when studied in CHCl3. We reasoned that by
modifying the electronics of the system and exploiting coop-
erative effects, we could overcome this deficiency. As dis-
cussed below, large enhancements in the response sensitivi-
ty—up to 1000-fold in the most favorable cases—have now
been successfully achieved by replacing the TTF subunits
originally used to construct 4 with the electronically modi-
fied aromatic thiophene and benzene TTF subunits. Specifi-
cally, we have found that the resulting annulated TTF-cal-
ix[4]pyrroles, receptors 5 and 6 (Scheme 1), display unique
Results and Discussion
With the above considerations in mind, the new thieno- and
benzo-annulated TTF-calix[4]pyrrole derivatives 5 and 6
were targeted for synthesis. Preliminary DFT calculations
(see the Supporting Information) led to the consideration
that the requisite precursors, namely 2 and 3, differ from 1
in terms of their p-electron donating properties (energies of
Scheme 2. Proposed origin of the positive homotropic allosteric effect seen when receptors 4, 5, and 6 are titrated with the test nitroaromatic explosives
TNB, TNP, and TNT.
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849

J. L. Sessler, J. O. Jeppesen et al.
their respective HOMOs). Specifically, these systems are
predicted to be somewhat less electron-rich. Thus, in the ab-
sence of compensating size and shape complementarity ef-
fects and the associated benefits of cooperativity as per
Scheme 2, it was expected that the receptors derived from
these precursors (i.e., 5 and 6) would be less effective than
4. As detailed below, this did not prove to be the case.
As shown in Scheme 1, receptors 5 and 6 were prepared
in 15% and 21% yield, respectively, from the trifluoroacetic
acid (TFA) catalyzed condensation of 2 and 3, respectively,
with an excess of Me2CO at room temperature in CH2Cl2.
Under these same conditions, receptor 4 was obtained in
18% yield from 1. Whereas 1 and 4 are known substances,[6]
compounds 2, 3, 5, and 6 have not been reported in the liter-
ature.
Although known to exist in several limiting conformations
(e.g., 1,2- and 1,3-alternate, partial-cone, cone), in the ab-
sence of a strongly bound substrate calix[4]pyrroles typically
adopt the so-called 1,3-alternate conformation.[7] It is this
conformation that, in the case of 4, was found to favor TNB
binding.[6] It is thus worth noting that all three receptors
(i.e., 4, 5, and 6) adopt 1,3-alternate conformations in the
solid state. Such a conclusion is established by X-ray struc-
tural analyses, which revealed the presence of two bound
Me2CO molecules in the case of 6 and two included MeOH
molecules for 5; in both cases, these solvent molecules are
bound through hydrogen-bond interactions and are held
within the two cliplike cavities defined by the calix[4]pyrrole
framework in this conformation (see Figure 1 and the Sup-
porting Information).[8] While not unexpected given the
chemistry of calix[4]pyrroles, such findings were thought to
augur well for the use of these systems as receptors for ni-
troaromatic substrates.
single crystal X-ray diffraction analysis of the 1:2 complex
6·2TNP. The resulting structure (Figure 1, bottom) revealed
that two molecules of TNP are located on opposite sides of
the central calix[4]pyrrole core and that both guests are
fully “sandwiched” within the two cavities provided by the
overall 1,3-alternate conformation. The short distances of
3.2809(74)–3.4900(75) ꢁ between the two imaginary planes
defined by the electron-rich benzo-TTF-pyrroles and the
electron-deficient TNP guest are fully consistent with strong
face-to-face p electron donor–acceptor interactions.[9] For
each of the TNP guests, hydrogen-bond interactions are
present between the oxygen atoms of the nitro groups in the
2- and 4-positions of the TNP guests and two of the pyrrolic
protons provided by the tetra-benzo-TTF-calix[4]pyrrole re-
ceptor 6 (the relevant distances range from 2.9215(86)–
3.2044(97) ꢁ). X-ray crystallographic studies of the com-
plexes formed between 4 with TNT and TNB[6] also revealed
that these latter substrates are likewise fully “sandwiched”
within the two cavities defined by the 1,3-alternate confor-
mation of receptor 4 (see the Supporting Information).
The interaction of the three TTF-calix[4]pyrroles with the
test nitroaromatic explosives TNB, TNP, and TNT was fur-
ther investigated through visible spectrophotometric titra-
tion experiments carried out in CHCl3 solution. The guest
binding events were easily visualized by following the pro-
gressive color change produced as the test nitroaromatic ex-
plosives were added to receptors 4–6. Plots of the associated
changes in absorption intensity as a function of TNB, TNP,
or TNT concentration were then used to construct binding
isotherms (see the Supporting Information).
As can be seen from an inspection of Figure 2, the titra-
tion isotherms were characterized by a sigmoidal curvature,
as would be expected for a cooperative binding process.
Such presumed cooperative binding was particular evident
in the case of receptor 5. In all cases, however, the allosteric
nature of the interaction was fully analyzed by using the
Hill equation,[10] Scatchard plots,[11] and non-linear regres-
sions of the two-site Adair equation.[12] These results provid-
ed support for a 1:2 host–guest binding mode. Job plots[13]
were also constructed, and these were fully consistent with
the proposed 1:2 host–guest stoichiometry (see the Support-
ing Information).
Initial evidence that the new calix[4]pyrrole derivatives 5
and 6 could complex nitroaromatic guests came from a
Linear Hill plots (log(Y/
N
(where Y, n, and Ka are the fractional saturation of host, the
Hill coefficient, and the association constant, respectively)
corresponding to each individual titration isotherm with a
satisfactory correlation coefficient (R>0.99) were then
made. From the slopes and the intercepts of these plots,
both the association constants (Ka) and the Hill coefficients
(n) were obtained. As summarized in Table 1, the values of
the Hill coefficients ranged from 1.23 to 1.86 (vs. a mathe-
matical limit of 2.0 for a perfectly cooperative two-site re-
ceptor binding two molar equivalents of an identical sub-
strate). Further evidence for the proposed allosterism came
from an upward curvature in Scatchard plots, which is a
characteristic of positive cooperativity (see the Supporting
Information).
Figure 1. X-ray crystal structure of 6·2Me2CO (top) and 6·2TNP
(bottom) shown with the thermal ellipsoids at 30%.[8]
850
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Colorimetric Chemosensors
FULL PAPER
nism proposed in Scheme 2, we suggest that the origin of
the positive cooperative binding seen for the interaction of
TNB, TNP, and TNT with 4, and to a greater extent for 5
and 6, reflects the fact that the binding of a first equivalent
of an electron-deficient guest forces the inherently flexible
(and normally conformationally mobile) calix[4]pyrrole re-
ceptor to adopt a more rigidified 1,3-alternate conformation.
This leads to a loss of rotational freedom and provides a
pre-organized framework for the subsequent binding of an-
other equivalent of the guest. It is an enhancement in this ri-
gidity, resulting from the replacement of the freely rotating
thiopropyl substituents with rigid aromatic rings whose
shape and electronic features match well the targeted sub-
strates, to which we ascribe the greater efficacy of the new
receptors 5 and 6 relative to 4.[15]
Based on the quantitative analyses summarized in
Table 1, receptor 5 was found to display the highest degree
of positive homotropic allostery across the board, with in
general, the sequence 5 > 6 > 4 being observed in terms of
the manifest cooperativity. Receptor 5 also displays the
highest relative affinity for all three electron-deficient
guests, as reflected in the fact that significantly larger Ka
values (as derived from the Hill analyses) are obtained for 5
than for 4 or 6. The Ka ratios are also calculated; this was
done by dividing the Ka values of 5 by those of 4 and 6, re-
spectively. The values found in this way were 790 and 23
(TNB), 973 and 41 (TNP), and 70 and 2 (TNT), as would be
expected for a highly cooperative system. In all cases, the
greatest affinity was seen for TNP, with this species also
acting as the most efficient allosteric effector, as inferred
from both the Hill coefficients and the K2/K1 ratios (TNP >
TNB > TNT).
It is important to appreciate that although the calix[4]pyr-
role 5 was found to bind the test substrates TNB, TNP, and
TNT with greater affinity than the benzo-fused system 6,
this latter was a considerably more effective receptor than 4.
In fact, in comparison with the first generation system 4, the
new annulated TTF-calix[4]pyrrole derivatives 5 and 6 dis-
play significantly enhanced binding constants for all three
nitroaromatic analytes (by up to three orders of magnitude).
As pointed out in the literature,[16] the strength of the p
donor–acceptor (D–A) complexation is governed not only
by the electron-donating properties, as gauged by the first
redox potential, but also by the overlap integral between
the donor and acceptor. In spite of the finding that the first
half-wave oxidation potential of receptor 4 obtained by
cyclic voltammetry (E11/2 =0.29 V in CHCl3 vs. SCE) is
lower than that of either 5 (E11/2 =0.37 V in CHCl3 vs. SCE)
or 6 (E11/2 =0.30 V in CHCl3 vs. SCE), significantly enhanced
binding of 5 and 6 compared to 4 toward nitroaromatic ex-
plosives is seen (see the Supporting Information). This is as-
cribed to the larger area and more suitable orientation of
the receptor p surfaces, as well as the cooperative effects
that underlie the overall two-step binding process (see
above).
Figure 2. Binding curves obtained from the visible spectroscopic titration
of receptors 4 (0.2 mm, g), 5 (0.2 mm, a), and 6 (0.2 mm, c) with
~
&
*
increasing amounts of TNB ( ), TNP ( ), and TNT ( ) in CHCl3 at
room temperature (symbols) and the calculated binding isotherms de-
rived by using the two-site Adair equation.[12] The y axis denotes the frac-
tional saturation of receptors 4, 5 and 6.
Table 1. Microscopic association constants[a] and cooperativity parame-
ters for receptors 4, 5, and 6, as obtained from fits to the Hill[10] and
Adair[12] equations.
Ka [mÀ2
]
n
K1 [mÀ1
]
K2 [mÀ1
]
K2/K1
4·2TNB
4·2TNP
4·2TNT
5·2TNB
5·2TNP
5·2TNT
6·2TNB
6·2TNP
6·2TNT
4.3ꢂ103
3.8ꢂ103
3.3ꢂ102
3.4ꢂ106
3.7ꢂ106
2.3ꢂ104
1.5ꢂ105
9.1ꢂ104
1.2ꢂ104
1.27
1.30
1.23
1.70
1.86
1.45
1.34
1.34
1.31
3.9ꢂ102
2.8ꢂ102
5.9ꢂ101
1.3ꢂ103
6.4ꢂ102
3.2ꢂ102
2.8ꢂ103
1.7ꢂ103
5.7ꢂ102
1.4ꢂ103
1.2ꢂ103
2.0ꢂ102
3.1ꢂ104
2.0ꢂ104
2.8ꢂ103
1.7ꢂ104
1.1ꢂ104
2.6ꢂ103
3.6
4.1
3.3
24
31
10
6.2
6.5
4.5
[a] Estimated errors for calculated binding constants are within 12%.
The binding data were also fitted to the two-site Adair
ACTHNUTRGNEUNG
equation (Y=(K’1[G]+2K’1K’2[G]2/(1+K’1[G]+2K’1K’2[G]2)
where K’1 and K’2 are macroscopic Adair constants and [G]
is the concentration of the explosive in question); this al-
lowed the determination of the individual microscopic bind-
ing constants K1 and K2 and the ratio K2/K1.[4,14] These latter
values, included in Table 1, were found to range from 3.3 to
31 (correlation coefficients R>0.99). Compared to the theo-
retical value expected for a non-cooperative system in the
case of identical and independent binding sites (K2/K1 =
0.25), these high values provide additional support for the
proposed positive homotropic allosteric nature of the bind-
ing process. Finally, a good agreement was found between
the values of the Hill coefficients for each receptor–sub-
strate pair and the corresponding K2/K1 ratio (and vice
versa) as shown in Table 1.
These findings are rationalized in terms of the effects of
aromatic annulation. Specifically, in accord with the mecha-
The high affinities displayed by the new receptors 5 and 6
led us to consider that they might act as improved colori-
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851

J. L. Sessler, J. O. Jeppesen et al.
metric chemosensors (“sensors”) for TNB, TNP, or TNT, ef-
fective even in the presence of competing anions or in the
presence of H2O. In fact, from the linear region of spectro-
scopic titration curves at receptor concentrations of 0.2 mm,
detection limits in the low sub-ppm levels were estimated
for the test nitroaromatic explosives (TNB: 0.44, 0.30,
1.56 mgmLÀ1; TNP: 0.77, 0.64, 2.68 mgmLÀ1; TNT: 3.04, 2.72,
15.3 mgmLÀ1, for receptors 6, 5, and 4, respectively). To test
further their utility as possible sensors, 0.1 mm CHCl3 solu-
tions of 4, 5, and 6 were mixed with 0.2 mm aqueous solu-
tions of the three test nitroaromatic explosives. As can be
seen in Figure 3, these additions result in an immediate
Conclusions
In summary, we have successfully demonstrated that the af-
finity of TTF-calix[4]pyrrole derivatives for nitroaromatic
explosives can be significantly enhanced through electronic
modulation of the parent TTF-pyrrole and the action of pos-
itive allosterism. As far as we are aware, this is the first syn-
thetic artificial receptor that displays biommetic positive ho-
motropic allostrism in the binding process of nitroaromatic
explosives. It is also the first that can operate in an aqueous
environment free of potential interference from potentially
competing ions, such as chloride. While far less sensitive
than more complex methods, we believe that these novel
positive homotropic allosteric receptors may offer some ad-
vantages relative to current chemosensory technologies,[20]
many of which still suffer from lack of selectivity and com-
plexity of setup and use. Work is thus underway to test
these systems more fully and to increase sensitivity through,
for example, incorporating of our new chemosensor materi-
als into various polymer matrixes.
Figure 3. Visual color changes induced by the addition of 2 mL of 0.1 mm
solutions of 4, 5, and 6 in CHCl3 to 3 mL of 0.2 mm aqueous solutions of
the test nitroaromatic explosives TNB, TNP, and TNT in the absence and
presence of salts. Here, “salts” refers to a mixture of NaHCO3, K2CO3,
MgSO4, CaCl2, and NH4Cl, 2 mm in each experiment. The contents of the
vials from left to right are as follows: 1) pure 4, 2) 4 + TNB, 3) 4 +
TNB + salts, 4) 4 + TNT, 5) 4 + TNP, 6) pure 5, 7) 5 + TNB, 8) 5 +
TNB + salts, 9) 5 + TNT, 10) 5 + TNP, 11) pure 6, 12) 6 + TNB, 13) 6
+ TNB + salts, 14) 6 + TNT, 15) 6 + TNP.
Experimental Section
General methods: All reagents were purchased from Aldrich and used
without further purification. 1H and 13C NMR spectra were recorded at
258C with a 500 MHz Varian Innova instrument. High Resolution ESI
mass spectrometry was performed using a Varian QF ESI 9.4 Tesla with
Internal Calibration.
change in the color of the CHCl3 solution, with the actual
variations depending on the specific choice of receptor and
explosives. Presumably, the observed color changes reflect
D–A interactions between the occupied HOMOs of TTF-
functionalized pyrroles to the empty p* orbitals of the nitro-
aromatic compounds. These interactions are expected to be
more favorable in the case of receptors that can provide for
a better spatial fit as noted above.
Compounds 1,[21] 4,[6] thieno
[1,3]dithiole-2-thione[23] were prepared according to literature procedures.
Synthesis of 2: A mixture of 5-tosyl-5H-[1,3]dithiolo[4,5-c]pyrrol-2-one
(3.11 g, 10 mmol) and thieno[3,4-d][1,3]dithiole-2-thione (3.61 g,
[1,3]dithiole-2-thione,[22] and benzo[d]-
ACHUTGTNRNEUG[N 3,4-d]ACHTUGNTRENNUGN
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
20 mmol) in neat triethylphosphite (150 mL) was stirred for four hours at
1408C and then cooled to room temperature. Addition of MeOH
(200 mL) to the reaction mixture led to precipitation of a yellow solid,
which was collected by filtration. The solid obtained in this way was puri-
fied by column chromatography (silica gel, CH2Cl2/hexane 2:1) to afford
the tosyl-protected compound 2a (2.04 g, 4.5 mmol, 42%). 1H NMR
(500 MHz, CDCl3): d=7.71 (d, J=8.29 Hz, 2H; Ar-H), 7.29 (d, J=
8.05 Hz, 2H; Ar-H), 6.92 (s, 2H; thiophene a-H), 6.85 (s, 2H; pyrrolic a-
H), 2.39 ppm (s, 3H; tosyl CH3). To a solution of 2a (2.04 g, 4.5 mmol) in
a mixture of methanol (100 mL) and THF (100 mL) sodium methoxide
(30% in MeOH, 10 equiv) was added. The mixture was heated to 508C
for 30 min and concentrated under reduced pressure until the volume
was 50 mL. The reaction mixture was poured into an aqueous solution of
NH4Cl (200 mL). The resulting yellow precipitate was collected by filtra-
tion and washed with water. The yellow solid obtained in this way was
purified by column chromatography (silica gel, CH2Cl2/hexanes 3:2) to
yield 2 as a yellow solid (1.28 g, 4.27 mmol, 95%). 1H NMR (500 MHz,
CDCl3): d=8.16 (brs, 1H; N-H), 6.84 (s, 2H; thiophen a-H), 6.59 ppm
(d, J=2.44 Hz, 2H; pyrrolic a-H); 13C NMR (500 MHz, CDCl3): d=
136.1, 123.2, 119.9, 119.7, 111.8, 109.7 ppm; HRMS (ESI): m/z: calcd for
C10H5NS5: 298.90200 [M+]; found: 298.90201.
Consistent with this conclusion is the finding that the aro-
matic-fused TTF-calix[4]pyrroles 5 and 6 displayed changes
that were significantly greater than those produced by the
first generation system 4. Furthermore, the addition of salts
(NaHCO3, K2CO3, MgSO4, CaCl2, and NH4Cl, each at a
concentration of 2 mm) to the aqueous phase failed to inhib-
it the colorimetric response.[17] This stands in marked con-
trast to what has been reported to be true for other colori-
metric nitroaromatic sensors, such as colored reaction-based
commercial field test kits,[5a,18] where the color change pro-
duced by formation of a Jackson–Meisenheimer anion when
nitroaromatic compounds are treated with strong bases, or
amine-functionalized Au nanoparticles[19] that rely on D–A
interactions between cysteamine and TNT and an aggrega-
tion-induced color change. These perceived advantages lead
us to suggest that compounds 5 and 6 could play a role as
chemosensors for nitroaromatic explosives, particularly
when a quick, qualitative response is needed that does not
rely on an instrumental response. It is to be noted, however,
that the latter methods are much more sensitive than even
the best of the new systems reported here, although those
do offer potential advantages in terms of ease of use.
Synthesis of 3: A mixture of 5-tosyl-5H-[1,3]dithiolo
ACHTUNGTREN[NUNG 4,5-c]pyrrol-2-one
(3.11 g, 10 mmol) and benzo[d][1,3]dithiole-2-thione (3.68 g, 20 mmol) in
AHCTUNGTRENNUNG
neat triethylphosphite (150 mL) was stirred for four hours at 1408C and
cooled to room temperature. MeOH (200 mL) was then added to the re-
action mixture, which led to precipitation of an orange solid, which was
collected by filtration. The resulting solid was purified by column chro-
matography (silica gel, CH2Cl2/hexane 3:2) to afford the tosyl-protected
compound 3a (2.82 g, 6.3 mmol, 63%). 1H NMR (500 MHz, CDCl3): d=
7.71 (d, J=8.42 Hz, 2H; tosyl), 7.28 (d, J=8.12 Hz, 2H; tosyl), 7.22 (m,
852
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Colorimetric Chemosensors
FULL PAPER
2H; benzene), 7.10 (m, 2H; benzene), 6.91 (s, 2H; pyrrolic a-H),
2.39 ppm (s, 3H; tosyl). To a solution of 3a (2.82 g, 6.3 mmol) in a mix-
ture of methanol (150 mL) and THF (150 mL) sodium methoxide (30%
in MeOH, 10 equiv) was added. The resulting mixture was heated to
508C for 30 min and concentrated under reduced pressure until the
volume was 50 mL. The reaction mixture was poured into an aqueous so-
lution of NH4Cl (200 mL). The yellow precipitate was filtered and
washed with water. The resulting yellow solid was purified by column
chromatography (silica gel, CH2Cl2/hexanes 2:1) to afford 3 as a yellow
solid (1.80 g, 6.13 mmol, 97%). 1H NMR (500 MHz, CDCl3): d=8.16
(brs, 1H; N-H), 7.23 (q, J=3.41 Hz, 2H; benzene a-H), 7.09 (q, J=
3.17 Hz, 2H; bezene b-H), 6.59 ppm (d, J=2.44 Hz, 2H; pyrrolic a-H);
13C NMR (500 MHz, CDCl3): d=136.5, 125.7, 121.8, 120.1, 119.9, 111.3,
109.6 ppm; HRMS (ESI): m/z: calcd for C12H7NS4: 292.9458 [M+];
found: 292.94558.
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[8] The crystal data and experimental details for the structural refine-
ment of 2, 3, 5·2MeOH, 6·2Me2CO and 6·2TNP are provided in the
Supporting Information. CCDC-739880 (2), CCDC-739877 (3),
CCDC-739876 (5·2MeOH), CCDC-739878 (6·2Me2CO), CCDC-
739879 (6·2TNP) contain the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
Synthesis of 5 and 6: general procedure for the synthesis of aromatic an-
nulated TTF-calix[4]pyrroles 5 and 6: Compound 2 (1.00 g, 3.34 mmol)
for 5, or compound 3 (1.00 g, 3.4 mmol) for 6 was dissolved in a mixture
of acetone (250 mL) and dichloromethane (250 mL) and the solution was
degassed with argon for 30 min before trifluroacetic acid (3 mL) was
slowly added. The mixture was stirred overnight at room temperature
before triethylamine (6 mL) was slowly added. After removal of the sol-
vent by evaporation, a solid yellow residue was obtained, which was
washed with water, dried in vacuo, and purified by column chromatogra-
phy (silica gel, CH2Cl2/hexanes 2:1) to give 5 (0.17 g, 0.13 mmol, 15%) or
6 (0.238 g, 0.178 mmol, 21%) as appropriate in the form of yellow solids.
1
For 5: H NMR (500 MHz, CDCl3): d=7.13 (brs, 4H; N-H), 6.74 (s, 8H;
thiophene a-H), 1.58 ppm (s, 24H; CH3); 13C NMR (500 MHz, CDCl3):
d=136.0, 127.0, 123.9, 123.6, 115.3, 111.6, 30.9, 27.6 ppm; HRMS
(MALDI): m/z: calcd for C52H36N4S20
:
1355.7346 [M+]; found:
1355.73487. For 6: 1H NMR (500 MHz, CDCl3): 7.14 (brs, 4H; N-H),
7.09 (m, 8H; benzene C-H), 6.95 (m, 8H; benzene C-H), 1.59 ppm (s,
24H; CH3); 13C NMR (500 MHz, CDCl3): d=136.4, 127.0, 125.5, 121.6,
118.2, 115.7, 112.2, 30.9, 27.6 ppm; HRMS (ESI): m/z: calcd for
C60H44N4S16: 1331.9121 [M+]; found: 1331.90918.
Acknowledgements
This work was supported by the US National Science Foundation (grant
no. CBET 0730053 to J.L.S.). We also gratefully acknowledge the Danish
Natural Science Research Council (FNU, projects no. 272-08-0047 to
K.A.N. and no. 272-08-0578 to J.O.J.), the Danish Strategic Research
Council in Denmark through the Young Researchers Programme (no.
2117-05-0115 to J.O.J.), and the Strategic Research Council in Denmark
through the Programme for Nanoscience, Technology, Biotechnology,
and IT (project no. 2106-07-0031 to J.O.J.). F.L.D. thanks the Delegation
Generale pour l’Armement (DGA/D4S) for financial support (project
ERE08.60.012).
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Received: October 29, 2009
Published online: December 9, 2009
854
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