Fluorescence sensing due to allosteric switching of pyrene functionalized cis-cyclohexane-1,3-dicarboxylate

Article abstract of DOI:10.1039/a705445i

The excimer/monomer fluorescence ratio for a pyrene functionalized cis-cyclohexane-1,3-dicarboxylate decreases upon titration with divalent and monovalent metal cations, as well as strong and weak acids.

Full text of DOI:10.1039/a705445i

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Fluorescence sensing due to allosteric switching of pyrene functionalized
cis-cyclohexane-1,3-dicarboxylate
Carol Monahan, Jeffrey T. Bien and Bradley D. Smith*†
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
The excimer/monomer fluorescence ratio for a pyrene
functionalized cis-cyclohexane-1,3-dicarboxylate decreases
upon titration with divalent and monovalent metal cations,
as well as strong and weak acids.
titration curve (Fig. 1) indicates that only 1 equiv. of nitric acid
is needed to completely switch the excimer/monomer
ratio. Thus, protonation of one of the carboxylates relieves the
strain due to dianionic repulsion and causes a flip to the alternate
chair conformation 4b. In contrast, alkali metal cations induce
much gentler decreases in excimer/monomer ratio suggesting a
gradual formation of 3b, where M is one or two M+ ions.§
Titration with ammonium chloride or ammonium nitrate
generated plots that were identical to the nitric acid curve
(Figs. 1 and 2). It appears that the ammonium also transfers a
proton to 2b and forms 4b. Although carboxylic acids are more
acidic than ammonium salts in aqueous solution, the reverse
order is observed in aprotic solvents such as MeCN. For
example, ammonium (pKa 16.5) is more acidic than glutaric
acid (pKa1 19.2, pKa2 29.9), a dicarboxylic acid that is
structurally related to 1.7–9
Molecules that can be chemically switched between different
conformations have been used as allosteric receptors, catalysts,
transport carriers, liquid crystalline materials and sensors.1 The
main approach with allosteric sensors has been to change the
proximity between two interacting fluorophores,2 or to alter the
solvent polarity surrounding a fluorophore.3 Here we describe
the allosteric properties of cis-1,3-disubstituted cyclohexane-
1,3-dicarboxylic acids 1 and in particular how the cis-
1,3-bispyrenyl derivative 1b acts as a fluorescent cations
sensor.4
Initially, the cis-1,3-dimethyl analogue 1a was prepared,†
and shown by 1H NMR spectroscopy to adopt a chair
conformation with both carboxyl groups in axial positions
(Scheme 1).§ This conformational preference is in agreement
with the higher steric A value for a methyl group compared to a
carboxy group. Conversion to the dianion results in a switch to
the alternate chair structure 2a with diequatorial carboxylate
groups.§ The driving force for this conformational change is the
electrostatic repulsion of the proximal anionic carboxylates. In
agreement with an earlier report by Menger et al., titration of a
1:1 MeOH–H2O solution of 2a with Mg2+ induces a conforma-
tional flip to 3a.6 Addition of Na+, however, has a negligible
effect on conformation in such a polar solvent. Two factors
drive the conformational change induced by Mg2+: (i) partial
neutralization of the anionic carboxylates by the Mg2+ ion, and
(ii) release of steric strain as the methyl groups transfer from
diaxial to more accommodating diequatorial positions.
2
1
0
0
1
2
3
4
Based on this knowledge it was hypothesized that compound
1b would show substantial changes in fluorescence upon
conformational switching. The two pyrenyl groups in structure
2b are in close proximity to each other and are able to exhibit
intramolecular excimer fluorescence. With structures 1b, 3b
and 4b, the pyrenyl groups are separated and the favorability of
excimer formation is decreased.2 This was found to be the case
in MeCN solution where titration of the bis(tetrabutylammon-
ium) salt of 2b with strong acid resulted in a stoichiometric
decrease in the excimer/monomer fluorescence ratio. The
Salt added (equiv.)
Fig. 1 Change in excimer/monomer ratio for 2b (3 mm) in MeCN upon
titration with (D) CsNO3, (x) RbNO3, (5) KNO3, (2) NaNO3, (-)
NH4NO3 and (+) HNO3. Excitation at 346 nm, monomer emission at 397
nm, excimer emission at 470 nm, T = 298 K.
700
600
500
400
–
CO2H
CO2H
CO2
Ha
–
CO2
CO2H
H +
Hb
R
R
–O2C
Ha
Ha
R
R
R
300
Hb
1a,b
Hb
4a,b
R
(a)
2a,b
M
200
100
0
(b)
(c)
(d)
–
a R = Me
CO2
–
b R =
CH2CH2CH2CH2
CO2
R
Ha
R
360 380 400 420 440 460 480 500 520 540
Hb
3a,b
l / nm
Fig. 2 Fluorescence emission for 2b in MeCN (3 mm, excitation at 346 nm)
in the presence of (a) 0, (b) 1.0, (c) 2.2 and (d) 10.6 mm of NH4NO3
Scheme 1
Chem. Commun., 1998
431

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0.5
Notes and References
† E-mail: smith.115@nd.edu
0.4
0.3
0.2
‡ Compound 1a was synthesized by treating dimethyl cyclohexane-
1,3-dicarboxylate with LDA (2 equiv). followed by Me2SO4 (2 equiv.). Sa-
ponification gave 1a in 40% overall yield. Similarly, compound 1b was
prepared by treating the di-tert-butyl cyclohexane-1,3-dicarboxylate with
LDA (2 equiv.) followed by 4-(pyren-1-yl)butyl trifluoromethylsulfonate (2
equiv.). Acid hydrolysis gave 1b in 15% overall yield.
§ The conformational assignments are based on the close homology of the
NMR data with Kemp et al. (ref. 5) and Menger et al. (ref. 6), who examined
the conformational switching of cis,cis-1,3,5-trimethylcyclohexane-
1,3,5-tricarboxylic acid (Kemp’s triacid). In particular, the non-equivalent
methylene protons between the two carboxy group in 1a (Ha and Hb)
resonate at d 2.63 and 1.13, respectively, in 1:1 MeOH–H2O (Dd = 1.50
ppm). The chemical shift for Ha is strongly deshielded due to the anisotropy
of the neighbouring carbonyl groups. In the case of dianion 2a, the
resonances for Ha and Hb are much closer together (Dd = 0.35 ppm)
indicating that they are nearly equidistant from the carboxylates, which can
only occur if the carboxylates have assumed equatorial positions. Structure
3 is drawn as a classical chair with the carboxylates in diaxial positions,
however, another possibility is a flattened half-chair which provides the
0.1
0
1
2
CaCl added (equiv.)
2
Fig. 3 Change in excimer/monomer ratio for 2b (3 mm in MeOH upon
titration with CaCl2. Excitation at 346 nm, monomer emission at 397 nm,
excimer emission at 470 nm, T = 298 K.
Strong evidence that the change in fluorescence is due to a
conformational change was obtained from the following control
experiments. (i) All of the fluorescence titrations were repeated
using tetrabutylammonium pyrene-1-butyrate as a replacement
fluorophore. In all cases, negligible changes in fluorescence
were observed, indicating that the excimer/monomer switching
is not due to due to intermolecular or environmental factors. (ii)
Treatment of a CD3CN solution of 1a with 2 equiv. of
tetramethylammonium hydroxide changes the difference in 1H
NMR chemical shifts for Ha and Hb Dd = 1.36 to 0.50 ppm,
which is consistent with a change from 1a to 2a.§ A subsequent
titration of this solution with ammonium thiocyanate results in
smooth migration back to Dd = 1.61 ppm, suggesting that 2a
becomes protonated and converts to 4a. The fluorescence
switching effects of ammonium and alkali metal cations are
essentially negligible in polar, competitive solvents such as
MeOH. However, moderate descreases in excimer/monomer
ratio are induced by titrating 2b with alkaline metal dichlorides
to produce 3b (Fig. 3).
In summary, a simple but sensitive allosteric system is
described that can undergo large changes in molecular
shape. Depending on the experimental conditions, the
conformational switching can be induced by divalent and
monovalent metal cations, as well as strong and weak
acids. Analogue 1b exhibits large changes in fluorescence and
is thus sensor for Lewis and Brønsted acids. Future efforts will
attempt to incorporate this conformational switch into the
structures of other molecular devices.
carboxylates
environments. (ref. 6).
with
slightly
more
spacious
psuedo-axial
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This work was supported by the National Science Foundation
(USA).
Received in Columbia, MO, USA, 28th July 1997; 7/05445I
432
Chem. Commun., 1998