Fluorescence modulation in anion sensing by introducing intramolecular H-bonding interactions in host-guest adducts

Article abstract of DOI:10.1039/b510795d

Fluorescence signaling in anion binding is modulated from quenching to enhancement by intramolecular H-bonding stabilization of anion-ionophore adducts; the intramolecular H-bonding is suggested to suppress the quenching processes otherwise possible and i

Full text of DOI:10.1039/b510795d

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Fluorescence modulation in anion sensing by introducing intramolecular
H-bonding interactions in host–guest adducts{
Yun Mi Chung, Balamurali Raman, Dae-Sik Kim and Kyo Han Ahn*
Received (in Cambridge, UK) 28th July 2005, Accepted 11th October 2005
First published as an Advance Article on the web 16th November 2005
DOI: 10.1039/b510795d
Fluorescence signaling in anion binding is modulated from
quenching to enhancement by intramolecular H-bonding
stabilization of anion–ionophore adducts; the intramolecular
H-bonding is suggested to suppress the quenching processes
otherwise possible and increase the conformational rigidity of
the anionic adducts, leading to fluorescence enhancement in a
selective fashion towards cyanide ion, among the various
anions examined.
The paramount importance of anions in the fields of medicine,
biology and environmental pollution is ubiquitous; to mention two
examples, the acute toxic effects of cyanide ions and the role of
phosphate ions in DNA recognition.1 Thus, the molecular
Fig. 1 Structures of ortho-TFADA (1), and reference compounds 2 and 3.
recognition and sensing of anions have been a subject of intense
together with good guest selectivity. To the best of our knowledge,
research in multiple disciplines. As a result, a variety of anion
such a modulation of fluorescence in anion sensing by utilizing
recognition and sensing systems have been developed, such as
intramolecular H-bonding interactions in host–guest adducts is
hosts having positively-charged organic and organometallic
unprecedented.
ligands.2 Recently, we introduced a novel anion recognition motif
We reasoned that the dansyl sulfonamide proton of ortho-
based on
a
neutral trifluoroacetophenone ionophore3 that
TFADA can play a dual role: it can bestow H-bonding assistance
to the TFA group for anion binding, as in the case of the
carboxamide group in our previous report,4 and more importantly,
it may modulate the fluorescence signaling by stabilizing its anionic
adduct. In the absence of such H-bonding stabilization, as in the
case of dansyl derivative 3, fluorescence quenching results because
an anion guest interacts with the acidic sulfonamide proton.
Similarly, fluorescence quenching would also result in the case of
‘‘non-stabilized’’ anionic adducts, such as from a para analogue of
1, para-TFADA (2), as confirmed in this study. We also reasoned
that the fluorescence intensity of an ortho-TFADA adduct may
also increase upon adduct formation owing to the increased
conformational rigidity8 due to H-bonding stabilization.
Furthermore, high guest selectivity may result in this type of
sensing system because the signaling of the complexation process is
likely to be dependent on the nature of the adducts from different
guests.
recognizes anions through reversible adduct formation. We have
shown that by introducing a H-bonding donor, such as an ortho-
carboxamido group, into the system, its binding affinity can be
significantly enhanced to a useful level towards anions such as
carboxylate and cyanide.4 In our search for chemical sensors, we
envisaged that the concept of intramolecular H-bonding stabiliza-
tion5 of anion–ionophore adducts may be extended to the
development of fluorescence sensors, not simply for the enhance-
ment of binding affinity but also for a dramatic modulation of
fluorescence. We wish to report herein the modulation of
fluorescence signaling in anion binding through intramolecular
H-bonding interactions in anion–ionophore adducts, which, in
particular, induces fluorescence enhancement rather than quench-
ing, a highly desirable but rather challenging task in the
development of anion sensors.6
The designed sensor, ortho-TFADA (1), consists of a trifluoro-
acetyl (TFA) moiety as the binding site and a dansyl (DA) moiety7
as the signaling unit (Fig. 1). ortho-TFADA-signaled anion
binding occurs with changes both in emission maximum
(hypsochromic shift) and fluorescence intensity (enhancement),
The desired ortho-TFADA and reference compounds 2 and 3
were synthesized by simple and straight-forward means.{ The
photophysical properties of ortho-TFADA were evaluated in
CH3CN. The absorption spectrum of ortho-TFADA displayed
strong absorption maxima at 260 and 350 nm, characteristic of the
dansyl moiety. When excited at 350 nm, ortho-TFADA showed
strong fluorescence emission at 530 nm, as expected.7
Department of Chemistry and Center for Integrated Molecular Systems,
Division of Molecular and Life Science, POSTECH, San 31,
Hyoja-dong, Pohang, 790-784, Republic of Korea.
E-mail: ahn@postech.ac.kr; Fax: (+82) 54 279 3399;
Tel: (+82) 54 279 2105
{ Electronic supplementary information (ESI) available: Synthesis and
characterization of compounds 1–3, 1H NMR spectra of free 1 and its
cyanide adduct, and few selected fluorescence titration plots. See DOI:
10.1039/b510795d
The anion sensing ability of 1 was evaluated by fluorescence
titration against increasing concentrations of each anion (as
tetrabutylammonium salts) in CH3CN. In line with our expecta-
tions, in the case of 2CN, we observed a 5-fold fluorescence
enhancement against sensor 1, accompanied by a hypsochromic
186 | Chem. Commun., 2006, 186–188
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Scheme 1 A plausible equilibrium between ortho-TFADA (1) and a
cyanide ion.
ortho-TFADA is stabilized via intramolecular H-bonding and thus
is less acidic than that of its para analogue. The intramolecular
H-bonding seems to perturb the molecular orbital of the alkoxide
adduct in such a way that possible quenching processes, otherwise
effective in the absence of such H-bonding, are diminished.§ In
addition, the conformational rigidity of a six-membered cyclic
intermediate of type I, via the intramolecular H-bonding, could
partially account for the enhanced fluorescence.8,10
Fig. 2 (a) Fluorescence titration of 1 (20 mM) with increasing amounts of
cyanide ion. Inset: dependence of fluorescence intensity (I/Io) with respect
to [CN2]/[ortho-TFADA]; (b) Collected emission plots obtained for an
equimolar mixture of 1 (20 mM) and each of the anion guests.
The formation of cyanide adduct I is evident from NMR
analyses. Upon 1 : 1 adduct formation, the sulfonamide NH
proton shifted downfield (Dd = 3.6) and the TFA carbonyl carbon
in 1 at d 182.8 disappeared. Also, the CF3 group showed an upfield
shift (Dd = 10.6) in its 19F NMR spectrum. Additionally, the
hypsochromic shifts in the fluorescence emission maximum of
ortho-TFADA in the presence of anions augment the evidence for
adduct formation (Fig. 2b). The anionic adduct formation seems
to perturb the energy gap between S1 and S0 states, thus resulting
in the hypsochromic shift, although such an explanation would
warrant further study. It can be understood that anions which did
not show any hypsochromic shift (2SCN, HSO42, Cl2, Br2) did
not form adducts of type I. Furthermore, we have already
demonstrated that a carboxamide proton ortho to the trifluoro-
acetyl group enhances its binding ability towards various anions, in
which we have realized the highest stabilizing effect for a cyanide
ion.4 Therefore, the fluorescence behavior of ortho-TFADA
towards anions can be explained, based on the relative affinity
of the anions for the trifluoroacetyl group, i.e., the ‘‘carbonyl
affinity’’ and the nature of the adduct formed."
shift (up to 36 nm) (Fig. 2a). The selectivity and sensitivity of 1
towards various anions are collectively presented in Fig. 2b. As can
be seen, AcO2 and F2 displayed rather weak fluorescence
enhancement (y2 times) with the same hypsochromic shift
2
(y32 nm), while H2PO4 showed even weaker enhancement.
For the other anions examined (HSO42, ClO42, F2, Cl2, Br2 and
2SCN), the fluorescence emission spectrum of 1 remained almost
undisturbed. It is worth mentioning that none of the anions
resulted in the fluorescence quenching of 1.
Being cognizant of the selective behavior of our sensor ortho-
TFADA, we set about ascertaining the role of its sulfonamide
proton in the observed fluorescence enhancement towards 2CN:
its fluorescence behavior towards 2CN can be compared with that
of para analogue 2, in which case fluorescence quenching was
observed. The result indicates that the anionic species resulting
from the interaction of para-TFADA with the cyanide ion shows
fluorescence quenching behavior.9 Therefore, the contrasting
fluorescence behavior of ortho-TFADA and para-TFADA in the
presence of 2CN indicates that the ortho sulfonamide proton plays
a vital role. Based on the results of para-TFADA, the carbonyl
addition intermediate, such as I, only stabilized by intramolecular
H-bonding in case of ortho-TFADA, should be responsible for the
observed fluorescence enhancement (Scheme 1), whereas another
possible intermediate, II, would show fluorescence quenching.
The formation of adduct I should thus be favored over the
possible deprotonation process that leads to II, as confirmed by
NMR analyses. It should be noted that the sulfonamide proton in
The association constant for the complexation process of ortho-
TFADA with cyanide ion (Kass = 3 6 105 M21) was obtained
from the observed fluorescence enhancement data.I
The ability of ortho-TFADA to signal selectively the binding of
2CN was checked in the presence of an excess of competing
anions. Fluorescence enhancement was observed under such
conditions, albeit slightly lower (80% enhancement compared to
that observed in the absence of the competing anions). This
property of our sensor makes it attractive. Although the present
sensor has poor water solubility, thus hampering its study in
aqueous media, we are very much aware that this type of signaling
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mechanism, involving intramolecular H-bonding, should work
well in aqueous media** which would lead to the development of a
selective cyanide sensor of practical utility.
In summary, we have demonstrated for the first time that the
fluorescence signaling of anion binding can be modulated by
intramolecular H-bonding stabilization of anion–ionophore
adducts. Through this approach, fluorescence enhancement rather
than quenching is realized in anion sensing using a neutral organic
sensor. The fluorescence enhancement observed is attributed to the
stabilization of the anion–ionophore adducts from possible
quenching processes, in addition to the conformational restrictions
imposed by the intramolecular H-bonding. The present system
also shows noticeable cyanide selectivity in acetonitrile and is
expected on rational grounds to be integrated into a new sensor
system effective in water that is under active investigation.**
This work was financially supported by KOSEF through the
Center for Integrated Molecular Systems.
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Notes and references
{ Selected data for 1: Yellow solid; mp 169.3–169.6 uC; 1H NMR
(300 MHz, CDCl3) d 2.85 (s, 6 H), 7.04 (t, J = 7.8 Hz, 1 H), 7.11 (d, J =
7.8 Hz, 1 H), 7.51 (t, J = 8.1 Hz, 2 H), 7.59 (t, J = 8.1 Hz, 1 H), 7.71 (d, J =
8.7 Hz, 1 H), 7.77 (d, J = 6.3 Hz, 1 H), 8.27 (d, J = 8.7 Hz, 1 H), 8.37 (d,
J = 7.5 Hz, 1 H), 8.54 (d, J = 8.7 Hz, 1 H) and 10.94 (br s, 1 H); 13C NMR
(75 MHz, CDCl3) d 183.5, 183.0, 182.6, 182.1 (q, J = 34.9 Hz), 152.3, 142.8,
137.4, 133.8, 132.3, 132.2, 132.1, 132.0 (q, J = 4.1 Hz), 130.8, 130.1, 129.5,
129.2, 123.1, 122.6, 118.7, 118.5, 118.4, 115.8, 115.7, 114.5 and 45.6; 19F
NMR (282 MHz, CDCl3) d 6.66; HRMS (EI) calc. for C20H17F3N2O3S
(M+) 422.0912, found (m/z) 422.0891. Selected data for 2: Pale green solid:
mp 66.8–67.0 uC; 1H NMR (300 MHz, CDCl3) d 2.86 (s, 6 H), 7.19–
7.13 (m, 3 H), 7.57–7.53 (m, 2 H), 7.86 (d, J = 8.1 Hz, 2 H), 8.32 (d, J =
8.7 Hz, 1 H), 8.37 (d, J = 8.2 Hz, 1 H) and 8.56 (d, J = 8.4 Hz, 1 H); 13C
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§ Acetate and phosphate ions also gave similar fluorescence quenching with
para-TFADA and N-Ph-DA. A PET-type process may be suggested as a
fluorescence quenching mechanism for these species.
" The cyanide adduct of 1 showed a higher quantum yield (W = 0.15) than
that of the acetate adduct (W = 0.04). It should be also noted that the
quantum yield of 1 itself (and also 2) was much lower (W = 0.006) than that
of its cyanide adduct, and N-Ph-DA that has no trifluoroacetyl group (W =
0.27).
I In the case of the acetate ion, the binding constant could not be
determined under an assumption of 1 : 1 binding, from which we infer that
at any given time, there exist more than two fluorescing species, probably
due to intermolecular H-bonding interactions. A complete mechanistic
study will be detailed separately in a full account.
** Usually, polar solvents are known to compete more with intermolecular
H-bonding interactions than intramolecular H-bonding. We have found
that a chromogenic sensor based on TFACA shows a dramatic anion
selectivity in an aqueous media. This will be published elsewhere.
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188 | Chem. Commun., 2006, 186–188
This journal is ß The Royal Society of Chemistry 2006