Towards the development of colorimetric probes to discriminate between isomeric dicarboxylates

Article abstract of DOI:10.1002/anie.200390178

Discrimination of isomeric anions: The selective, shape-controlled colorimetric sensing of dicarboxylate ions has been achieved and represents a development in the "naked-eye" detection of certain organic isomers. The photograph shows the diverse colors o

Full text of DOI:10.1002/anie.200390178

Angewandte
Chemie
Instruments TGA-2050 apparatus (nitrogen flow 60 mlminꢀ1
,
ation with the target guests, one or several macroscopic
28Cminꢀ1).
properties in response to the molecular coordination event.
Changes in fluorescence[2] and in absorbance[3] are the output
signals used in the development of optical chemosensors.
Although a number of chromogenic receptors for the sensing
of metal ions have been developed,[4] very few chromogenic
receptors for anions have been described in the literature that
are based on recognition approaches.[5] Most of the receptors
have been developed for the colorimetric sensing of inorganic
anions,[6] whereas very few have been designed for recogni-
tion of organic anions,[7] particularly in aqueous environ-
ments. Thus, the development of chromogenic reagents for
such species remains a challenge. In this context, and as an
advancement of this field, we wish now to report a chromo-
genic system for the colorimetric discrimination between
certain organic isomers (cis/trans and ortho/meta/para dicar-
boxylates). Differentiation of isomers is, in general, a difficult
task because of their rather similar chemical and physical
properties. To the best of our knowledge, the examples we
show here are the first supramolecular-based colorimetric
probes for the detection of isomeric anions.
Most of the known colorimetric anion chemosensors are
based on host molecules containing anion coordination sites
coupled to chromogenic signaling units. In those receptors,
coordination of the anion usually modifies the charge-transfer
band of the chromogenic group resulting in ™naked-eye∫
anion detection. A different approach involves the use of
anion-induced reactions that can be either reversible or
irreversible.[8] We have recently reported the use of one such
anion-induced reversible reaction for the selective detection
of ATP in water/organic solvent mixtures.[9] The system was
based on the cyclization of yellow 1,3,5-triarylpent-2-en-1,5-
diones to the magenta pyrylium cation. A family of 1,3,5-
triarylpent-2-en-1,5-diones were synthesized by electrophilic
aromatic substitution of the corresponding aniline derivative
with 2,6-diphenylpyrylium perchlorate in DMF at 1508C.
Subsequent column chromatography on aluminum oxide
afforded the receptors L1 L8 in approximately 35% yield.
The UV/Vis spectra of L1 L8 are very similar, with a band
centered at around 370 380 nm, which is indicative of their
brightly yellow color. The structures of the compounds L1 L8
are shown in Scheme 1.
[13] The BET surface area of the sample activated at 1708C under
vacuum for 64 h was studied on a Micromeritics ASP200
porosimeter.
[14] Magnetization measurements were performed on a Quantum
Design Squid magnetometer (MPMS-5).
[15] G. Fÿrey, R. de Pape, M. Leblanc, J. Pannetier, Rev. Chim. Miner.
1986, 23, 474 484.
[16] a) R. E. Morris, J. J. Owen, J. K. Stalick, A. K. Cheetham, J.
Solid State Chem. 1994, 111, 52 57; b) L. B. McCusker, R. W.
Grosse-Kunstleve, C. Bearlocher, M. Yoshikawa, M. E. Davis,
Microporous Mater. 1996, 6, 295 309; c) D. M. Poojary, A.
Cabeza, M. A. G. Aranda, S. Bruque, A. Clearfield, Inorg.
Chem. 1996, 35, 1468 1473; d) M. Louèr, C. Le Roux, J. Dubac,
Chem. Mater. 1997, 9, 3012 3016.
[17] T. Wessels, C. Baerlocher, L. B. McCusker, E. J. Creyghton, J.
Am. Chem. Soc. 1999, 121, 6242 6247.
[18] a) K. D. M. Harris, M. Tremayne, B. M. Kariuki, Angew. Chem.
2001, 113, 1674 1700; Angew. Chem. Int. Ed. 2001, 40, 1626
1651; b) E. Tedesco, G. W. Turner, K. D. M. Harris, R. L.
Johnston, B. M. Kariuki, Angew. Chem. 2000, 112, 4662 4665;
Angew. Chem. Int. Ed. 2000, 39, 4488 4491; c) E. Y. Cheung,
E. E. McCabe, K. D. M. Harris, R. L. Johnston, E. Tedesco,
K. M. P. Raja, P. Balaram, Angew. Chem. 2002, 114, 512 514;
Angew. Chem. Int. Ed. 2002, 41, 494 496; d) R. B. Von Dreele,
P. W. Stephens, G. D. Smith, R. H. Blessing, Acta Crystallogr.
Sect. D 2000, 56, 1549 1553.
Colorimetric Isomer Probes
Towards the Development of Colorimetric Probes
to Discriminate between Isomeric
Dicarboxylates**
Felix SancenÛn, RamÛn MartÌnez-MµÊez,* Miguel
Angel Miranda, Maria-Jesus SeguÌ, and Juµn Soto
Figure 1 shows a photograph of buffered dioxane/water
(70:30 v/v) solutions of L8 at approximately pH 6 (0.01m
HEPES buffer, HEPES = 4-(2-hydroxyethyl)-1-piperazine-
ethanesulfonic acid) containing an equimolar amount of
certain carboxylate (acetate, benzoate) and dicarboxylate
The development of new chemosensors based on supra-
molecular concepts is a field of current interest.[1]
A
significant amount of work has been devoted to obtain
specific chemosensors that are able to change, upon complex-
ꢀ
ꢀ
ꢀ
ꢀ
anions (terephthalate, OOC (CH2)n COO , n = 0 to 7,
oxalate, malonate, succinate, glutarate, adipate, pimelate,
suberate). The solution remains yellow upon addition of all
the above mentioned species, except for the oxalate and
malonate ions, whereby the solutions turn red-magenta. This
remarkable color change is, as stated above, a result of the
anion-induced selective cyclization of L8 to give the colored
2,4,6-triphenylpyrylium cation (absorption maximum at ap-
proximately 550 nm). Figure 1 also shows the color variation
observed upon addition of maleate or fumarate dicarboxylate
ions to buffered solutions of L5 (0.01m HEPES buffer,
approximately pH 6). The solution is yellow in the presence
[*] Prof. R. MartÌnez-MµÊez, F. SancenÛn, Prof. M. A. Miranda,
M.-J. SeguÌ, Dr. J. Soto
Departamento de QuÌmica
Universidad Politÿcnica de Valencia
Camino de Vera s/n, 46071 Valencia (Spain)
Fax: (+34)96-387-9349
E-mail: rmaez@qim.upv.es
[**] This research was supported by the Ministerio de Ciencia y
TecnologÌa (proyecto PB98-1430-C02-02, and AMB99-0504-C02-01).
F.S. thanks the Ministerio de Ciencia y TecnologÌa for a Doctoral
Fellowship. M.-J.S. thanks the Universidad Politÿcnica de Valencia
for a Doctoral Fellowship.
Angew. Chem. Int. Ed. 2003, 42, No. 6
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Communications
by Hamilton and co-workers, was carried out in dichloro-
methane[10] and, more recently, two reports by Anslyn and co-
workers have described chromogenic competition assays for
the colorimetric determination of citrate and tartrate species
in aqueous organic solvents.[11]
n
O
X
R2
X
R1
N
N
In addition to the use of L8 and L5 as receptors (Figure 1),
similar results are obtained when using the remaining
compounds outlined in Scheme 1, which strongly suggests
that the interaction of the anions with the receptors involves a
fragment that is common to all of them. This points to the
pent-2-en-1,5-dione group, rather than the aza-oxa- or aza-
thia-oxa-polyazaalkane fragments, acting as the anion binding
site. Thus, although diones can not bind to carboxylates, the
corresponding enol tautomers can form hydrogen bonds with
the anions (see the upper part of Scheme 2). From all the
dicarboxylates studied, only oxalate, malonate, and maleate
ions gave color variation. The special feature that these three
anions have in common is the presence of carboxylate groups
in close proximity. In this context, the potential ability of
these guests to bind the hydroxyl group of the receptor by
using both carboxylate groups would result in the formation
of stronger hydrogen bonds and, therefore, in an enhance-
ment of the nucleophilic character of the hydroxylic oxygen
atom. One might refer to this action as ™tweezers-like∫
behavior, in the sense that only diacids shaped like ™tweezers∫
are able to act as chelating ligands towards the OH group,
whereas other diacids or monoacids do not. Hence, the
recognition process conforms to the supramolecular concept
that guests (in our case anions) do not only have charge or
size, but also a certain shape (in this case, proximity
between carboxylate groups).[12] Scheme 2 de-
scribes the steps in the shape-induced recognition
process; the tweezers-like carboxylate groups serve
to disrupt the hydrogen atom from the hydroxy
oxygen atom, which induces nucleophilic attack at
the C1 carbon, with subsequent cyclization occuring
to give the magenta pyrylium cation.
O
O
O
O
L1, X = O, n = 1 L5, R1 = R2 = CH3
L2, X = O, n = 2
L3, X = O, n = 3
L4, X = S, n = 2
L6, R1 = CH2CH2OH, R2 =(CH2CH2O)2CH2CH2OH
L7, R1 = CH2CH2OH, R2 = (CH2CH2O)3CH2CH2OH
L8, R1 = CH2CH2OH, R2 = (CH2CH2O)4CH2CH2OH
Scheme 1. Schematic representation of L1 L8.
of the trans isomer, but changes color to magenta in the
presence of the cis isomer. As far as we know, this is the first
reported example of cis/trans discrimination using colorimet-
ric reagents. In fact, there are very few reports in the literature
dealing with the use of synthetically constructed receptors for
the colorimetric sensing of carboxylic acids. One such study,
Further studies also appear to support the
mechanism outlined in Scheme 2. Thus, if that
mechanism is correct, then the anions should be
acting as catalysts for the cyclization. This has been
confirmed, and we have found rate constants for the
process anion + L5!L5(cy) + anion of 149.3, 62.6,
and 148.7mꢀ1 sꢀ1 for oxalate, malonate, and maleate
ions, respectively. Furthermore, when kinetic stud-
ies were carried out in D2O/dioxane mixtures, the
rate constants were found to be 3 4 times smaller
than when water/dioxane was used as solvent. Such
an isotope effect suggests that the rate-determining
step of the cyclization reaction involves cleavage of
ꢀ
ꢀ
the O H (O D) bond.
Additionally, molecular modeling calculations
to study the interaction of the enol tautomer of L5
with different anions[13] have shown that when a
carboxylate is placed near the hydroxyl group of the
enol tautomer, a hydrogen bond is formed. How-
ever, the strength of the hydrogen bond depends on
the nature of the anions. The calculations show that
the oxalate, malonate, and maleate anions tend to
Figure 1. a) Color changes induced on L8 (5î10ꢀ5 moldmꢀ3) at pH 6 (buffered with 0.01m
HEPES) in dioxane/water (70:30 v/v) in the presence of (from left to right): no anion, oxalate,
malonate, succinate, glutarate, adipate, pimelate, suberate, terephthalate, acetate, and ben-
zoate anions. b) Color changes induced on L5 under the same conditions, in the presence of
(from left to right) maleate and fumarate anions.
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Angewandte
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H
R
O
R
O
Ph
Ph
O
O
Ph
Ph
O
O
O
O
O
O
O
H
O
R
O
Ph
O
Ph
– OH–
Figure 3. Visible spectra of L5 (5î10ꢀ5 moldmꢀ3) at pH 6 (buffered
with 0.01m HEPES) in dioxane/water (70:30 v/v) in the presence of
phthalate, isophthalate, and terephthalate anions.
R
O
O
+
O
O
Ph
O
+
Ph
experimental absorbance of the band at 550 nm after a
reaction time of 30 min (this absorbance indicates the extent
to which the magenta pyrylium cation is obtained). In fact, a
very good correlation is found. It is interesting that carbox-
ylates showing the above-described tweezers-like shape tend
to induce a significant increase in negative-charge density at
the oxygen atom of the hydroxyl group.
Scheme 2. Proposed mechanism of cyclization by nucleophilic attack
of the oxygen atom to the C1 carbon. The Scheme also shows the pro-
posed formation of hydrogen bonds between the dianion and the hy-
droxy group.
form strong hydrogen bonds, significantly enhancing the
electron density of the oxygen atom of the hydroxyl group.
This is shown in Figure 2, where the charge on the enolic
oxygen atom (from PM3calculations) of the L receptor
bound to the corresponding anion is plotted against the
Colorimetric recognition of the tweezers-like dicarbox-
ylates appears to be of general application (Figure 3), as the
yellow L1 L8 receptors also change color to magenta in the
presence of phthalate anions, whereas they remain yellow in
the presence of isophthalate or terephthalate anions (diox-
ane/water (70:30 v/v) solutions, 0.01m HEPES buffer, ap-
proximately pH 6).
5
In summary, the use of relatively simple receptors
combined with a specific anion shape allows remarkable
colorimetric recognition of certain organic guests in water/
dioxane mixtures. The recognition process, which is based on
the cyclization of 1,3,5-triarylpent-2-en-1,5-diones, has proved
to be very sensitive to the presence of tweezers-like carbox-
ylates. Thus, for the first time, shape-induced cyclization
allows for the design of probes for the selective colorimetric
recognition of certain organic isomers. For instance, receptors
L1 L8 are suitable chromogenic reagents for selective dis-
crimination between cis/trans dicarboxylates and ortho/meta/
para dicarboxylates in water/organic solvent mixtures at
nearly neutral pH values. We believe that the interaction of
target molecules with suitable chemical reactions, associated
with a color change, can play a significant role in the
development of a new generation of colorimetric sensors or
reagents for the detection of target organic guests.
Figure 2. Plot of the charge (q) on the oxygen atom of the hydroxyl
groupin the enol tautomer of L 5 after forming hydrogen bonds with
certain anions, as a function of the absorbance of the 550 nm band.
The charge q is calculated from PM3 calculations of the interaction of
L5 and the corresponding anion. All the anions studied form hydrogen
bonds with the hydroxyl group.
Received: September 3, 2002
Revised: November 7, 2002 [Z50095]
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Communications
Porphyrin-Containing [3]Rotaxanes
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Synthesis of Porphyrin-Containing [3]Rotaxanes
by Olefin Metathesis**
Ruud G. E. Coumans, Johannes A. A. W. Elemans,
Pall Thordarson, Roeland J. M. Nolte, and
Alan E. Rowan*
Rotaxanes are fascinating examples of interlocked molecules.
Their synthesis is now well-established, and a large variety of
interesting rotaxane-based architectures have been report-
ed.[1,2] Our interest in rotaxanes partly arises from the reports
by others on the synthesis of these molecules and their
application in molecular devices, but predominantly by the
impressive way nature makes use of catalytically efficient
(pseudo)rotaxane structures in processes such as DNA
replication and degradation.[3] In these structures the enzyme
(for example, DNA polymerase III)[3] completely encircles
the DNA strand and performs numerous rounds of catalysis
(for example, template polymerization or hydrolysis) on the
macromolecular substrate before dissociating from it. These
so-called processive enzymes are therefore very efficient.
Inspired by this concept, we have initiated a research project
to construct synthetic analogues of these processive enzymes.
For this purpose we have designed porphyrin host 1 (see
Scheme 1), which can form very stable 1:1 host guest com-
plexes with viologen derivatives (Kass > 106 mꢀ1),[4] and have
synthesized simple porphyrin-containing [2]rotaxanes.[5] It
was also shown that the manganese derivative of 1 is a very
active epoxidation catalyst.[6] A polymeric rotaxane with
double bonds in the polymeric thread and host 1 as the
circular component is needed to be able to construct a
processive mimic. The latter molecule can then slide over the
thread and epoxidize the double bonds (Figure 1). Herein we
report the synthesis of such a rotaxane molecule by using
olefin metathesis protocols.
[5] V. Amendola, L. Fabbrizzi, C. Mangano, P. Pallavicini, A. Poggi,
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[8] When the color change is coupled to an irreversible chemical
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™chromogenic dosimeter∫ (or ™chemodosimeter∫).
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Grubbs and co-workers have developed an elegant and
efficient route to synthesize end-functionalized polybuta-
dienes. They showed that an acyclic olefin can act as a chain
transfer agent (CTA) in the ring opening metathesis polymer-
ization (ROMP) of 1,5-cyclooctadiene (COD), using ruthe-
nium carbenes 2 and 3 (Scheme 1) as initiators.[7] The CTA is
incorporated at both ends of the polymer, with the average
number of end groups per polymer chain (Fn) being close to 2.
We decided to apply this protocol to synthesize the desired
[10] M. S. Goodman, A. D. Hamilton, J. Weiss, J. Am. Chem. Soc.
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[*] Dr. A. E. Rowan, R. G. E. Coumans, Dr. J. A. A. W. Elemans,
Dr. P. Thordarson, Prof. R. J. M. Nolte
Department of Organic Chemistry, NSRIM
University of Nijmegen
Toernooiveld, 6525 ED Nijmegen (The Netherlands)
Fax: (+31)24-3652929
E-mail: rowan@sci.kun.nl
[**] National Research School Combination Catalysis (NRSCC) is
acknowledged for financial support.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
650
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