Fluorescent receptor for dicarboxylates based on pyrrolecarboxamides

Article abstract of DOI:10.1080/10610278.2012.671523

Neutral ditopic and fluorescent receptor 1 based on two 2,5-pyrrolecarboxamide units shows a strong association with dicarboxylate anions such as glutarate and adipate through multiple hydrogen bonds. Fluorescence and ¹H NMR titrations display

Full text of DOI:10.1080/10610278.2012.671523

This article was downloaded by: [University of Regina]
On: 06 July 2013, At: 07:14
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Supramolecular Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/gsch20
Fluorescent receptor for dicarboxylates based on
pyrrolecarboxamides
M. Belén Jiménez a , Ángel L. Fuentes de Arriba a , Emilio Calle b & M. Cruz Caballero a
a Department of Organic Chemistry, University of Salamanca, Plaza de los Caídos 1-5,
E-37008, Salamanca, Spain
b Department of Physical Chemistry, University of Salamanca, Plaza de los Caídos 1-5,
E-37008, Salamanca, Spain
Published online: 11 Apr 2012.
To cite this article: M. Beln Jimnez , ngel L. Fuentes de Arriba , Emilio Calle & M. Cruz Caballero (2012) Fluorescent
receptor for dicarboxylates based on pyrrolecarboxamides, Supramolecular Chemistry, 24:5, 361-368, DOI:
10.1080/10610278.2012.671523
To link to this article: http://dx.doi.org/10.1080/10610278.2012.671523
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

Supramolecular Chemistry
Vol. 24, No. 5, May 2012, 361–368
Fluorescent receptor for dicarboxylates based on pyrrolecarboxamides
a
M. Belen Jimenez , Angel L. Fuentes de Arriba , Emilio Calle and M. Cruz Caballero *
a
b
a
´
´
´
a
b
Department of Organic Chemistry, University of Salamanca, Plaza de los Caıdos 1-5, E-37008 Salamanca, Spain; Department of
´
´
Physical Chemistry, University of Salamanca, Plaza de los Caıdos 1-5, E-37008 Salamanca, Spain
(Received 28 August 2011; final version received 13 February 2012)
Neutral ditopic and fluorescent receptor 1 based on two 2,5-pyrrolecarboxamide units shows a strong association with
dicarboxylate anions such as glutarate and adipate through multiple hydrogen bonds. Fluorescence and 1H NMR titrations
display a 1:1 stoichiometry for the complexes, with glutarate as the most strongly bound guest. Receptor 1 exhibits PET-
induced fluorescence quenching upon recognition due to the presence of a dansyl group. The synthetic methodology
described here might provide access to closely related receptors by the introduction of different fluorophores in the last step
of the synthesis.
Keywords: dicarboxylate recognition; fluorescent receptor; pyrrolecarboxamide; glutarate; adipate
1. Introduction
Host 1 is a symmetric ditopic receptor which
comprises two 2,5-amidopyrrole units (29) as binding
sites and a dansyl group as the fluorogenic moiety,
separated by a semi-rigid m-xylylendiamine spacer, the
same spacer previously used for the reported receptors, 2
and 3.
This structural arrangement provides two binding sites
with three directional NH-bonds each, which is able to
accommodate dicarboxylate guests forming up to six H-
bonds in the recognition process. Compared to previous
receptors 2 and 3, the hydrogen bonding array in receptor 1
has been extended from 4 to 6 H-bond donors, by
incorporation of two butylamide groups at position 5 of
each pyrrole unit. These two extra H-bonds will strengthen
the binding by further stabilisation of the complexes with
dicarboxylates.
Hydrogen bonds play a major role in biorecognition and
have inspired the design of multiple molecular hosts for
selective and strong binding of guest molecules (1–6).
Dicarboxylate anions are interesting targets in the field of
molecular recognition (7–10), because of their key
structural role and their biologically relevant functions
(regulation of metabolic processes, neurotransmitters . . . )
(8 , 11, 12). Therefore, a considerable effort has been made
to develop ditopic receptors for dicarboxylates based on
hydrogen bonds.
NH-based hydrogen bonding heterocyclic compounds
have been broadly employed as hosts for a variety of
molecules. Specifically, the ability of anion coordination
by receptors containing pyrrole groups has been reported
in the literature by Sessler, Jurzack, Gale and others (13–
20) applying simple pyrrole-based amide cleft species as
efficient receptors for anionic guests.
On the other hand, receptor 1 bears a dansyl group
appended as a fluorophore, thus constituting a fluorophore-
spacer-receptor (30, 31) system. The dansyl fluorophore is
connected to the receptor framework in a separate but
nearby position from the actual binding bis-amidopyrrole
arms. In recent years, recognition and sensing of
dicarboxylates have emerged as an attractive research
topic (32, 33) due to the key roles played by these anions.
The synthesis and molecular recognition properties of
receptor 1, containing six hydrogen bond donating groups
and a dansyl fluorophore, are reported here. Our interest is
focused on the study of association constants (Kass) for the
complexes with short-chain dicarboxylates such as
succinate, glutarate or adipate.
Additionally, fluorescence-based sensors (21–27)
have become an active area of research because they are
a valuable tool for the detection of neutral and ionic
species and they are particularly attractive owing to the
simplicity, high detection limit and low cost of the
technique. In the present work, we report the synthesis,
molecular recognition and fluorescent properties of host 1
(Figure 1), which is structurally closely related to the
previously reported ones, 2 and 3 (28) (X-ray, Figure 2).
Because only good results of fluorescence were obtained
with receptor 2 possessing the dansyl group, the acridine
derivatives have now been discarded.
*Corresponding author. Email: ccsa@usal.es
ISSN 1061-0278 print/ISSN 1029-0478 online
q 2012 Taylor & Francis
http://dx.doi.org/10.1080/10610278.2012.671523
http://www.tandfonline.com

´
M.B. Jimenez et al.
362
Figure 1. Proposed structures for the complexes stabilised with six and four H-bonds.
Figure 2. X-ray structures of receptors 2 (left) and 3 (right).
2. Results and discussion
correlations of NHs are included in Supplementary
Information, available online.
2.1 Synthesis of receptor 1
Receptor 1 was obtained in one-pot process by treatment of
the versatile key compound 9 (Figure 3), with tetrabuty-
lammonium fluoride (1 M, tetrahydrofuran (THF) sol-
ution), followed by the addition of dansyl chloride in 1,2-
dichloromethane. This versatile intermediate 9 might
provide access to various related pyrrolecarboxamide
receptors by the introduction of different fluorophores after
the deprotection of the corresponding TBDMS analogue 9.
Intermediate 9 was prepared by condensation of the
activated pyrrolo-succinimide derivative 7 with the m-
xylylenediamine derivative 8 (28) (see Figure 3 and
Experimental part) in the presence of triethylamine and 4-
DMAP in 1,2-dichloromethane. Furthermore, compound 7
was synthesised from 4 (34), as depicted in Figure 3.
All compounds were characterised by spectroscopic
2.2 1H NMR studies
The binding properties (35, 36) of receptor 1 with
succinate, glutarate and adipate anions as their diTBA salts
1
were investigated by H NMR titrations in CDCl3–4%
DMSO-d6 to ensure that receptor 1 was completely
dissolved during the experiments. Association constants
were determined under identical conditions as those used
previously for receptors 2 and 3 (28). Complexation
studies of dianions were performed carrying out titrations
at a constant concentration of receptor (1.0 £ 1023 M) by
the addition of increasing amounts of guest until
saturation. All the NH-protons were involved in the
association event according to the simultaneous downfield
shifts observed upon the formation of the complexes
(Supplementary Information, available online).
1
methods. H, 13C NMR, IR and resolution mass spectra
(HRMS) data are consistent with structure 1 (Supplemen-
tary Information, available online).
The stoichiometry of the complexes between receptor
1 and diTBA salts of glutarate and adipate was studied by
Job plot analysis (37, 38), revealing the maximum at a
molar fraction of 0.5 for each of them, from which the 1:1
binding stoichiometry can be inferred. The HRMS–
electrospray ionisation (ESI) showing the molecular ion
peak at m/z ¼ 1141.6418 (1 þ glutarate þ NBu4; see
In order to get more insight about the receptor 1
conformation, attempts to grow X-ray quality crystals of
the receptor or its 1:1 complexes with dicarboxylates were
tried, but they were not successful. Instead, a confor-
mational analysis of receptor 1 in DMSO solution was
carried out including ROESY experiments. NOE’s

Supramolecular Chemistry
363
Figure 3. Scheme of synthesis of 1.
1
Supplementary Information, available online) confirmed
the 1:1 stoichiometry of 1·glutarate complex, without the
appearance of significant signals for higher aggregates.
According to the 1H NMR titrations, 1 showed a higher
affinity for glutarate (Kass ¼ 1.2 £ 105 M21) than for
adipate (Kass ¼ 4.3 £ 104 M21). This result prompted us to
evaluate the binding ability of receptor 1 for diTBA
glutamate, due to the same length between the two
carboxylate groups. A slightly low Kass was obtained
(2.4 £ 104 M–1), as expected for a-aminoacids (Table 1).
On the other side, the titration data found with diTBA
succinate could not be fitted to a simple 1:1 binding model
and it was not possible to determine an accurate association
constant. Job’s plot analysis revealed the formation of
complexes with different stoichiometries. The different
behaviours of succinate as compared with glutarate and
adipate dianions were attributed to the different sizes of the
dicarboxylates. Probably, succinate is not large enough to
simultaneously bind to both binding sites in host 1.
In view of the high Kass values obtained, H NMR
titration experiments were also carried out in pure DMSO-
d6. In this solvent, the same trend for anion binding was
kept and titration data were well fitted to a 1:1 binding
model curve (39, 40). Compared with the titrations in
CDCl3–4% DMSO-d6 lower affinities were observed in
DMSO-d6, a more competitive solvent (41). However,
preference for glutarate over adipate was increased
reaching a factor of eight times (Kass ¼ 8.5 £ 104 M21
and Kass ¼ 1.1 £ 104 M21, respectively, Table 1). In all
cases, Kass values of 1 are greater than those obtained with
the previously cited receptor 2, as a result of the increased
number of H-bonds formed in the complexes.
Figure 4 shows the region between 5 and 16 ppm of the
1H NMR spectrum to illustrate the effect caused on
receptor 1 resonances by the addition of 1 equiv. of diTBA
glutarate in DMSO-d6. Different downfield shifts for the
three NHs involved in the complexation can be observed as
a consequence of the association process.
Table 1. Association constants of compounds 1 and 2 with anionic guests at 293 K.
Substratesa
Glutarate
Receptor
Kass (M21) 1H NMR titrations
Kass (M21) fluorescence titrations
1.1 £ 105b
4.0 £ 104b
1
2
1
2
1
1.2 £ 105b/8.5 £ 104c
8.9 £ 103b
Adipate
4.3 £ 104b/1.1 £ 104c
5.6 £ 103b
Glutamate
2.4 £ 104b
Note: Errors estimated to be not more than ^10%.
a Added as diTBA salts.
b CDCl3–4% DMSO-d6.
c DMSO-d6. In all cases, a 1:1 receptor:anion stoichiometry was observed.

´
M.B. Jimenez et al.
364
Figure 4. Comparison of the titration spectra between free receptor 1 (bottom) and after the addition of 1 equiv. of diTBA glutarate (top)
in DMSO-d6. In the figure, significant changes are highlighted.
The highest downfield shift, Dd ¼ 3.28 ppm, was that
of the NH pyrrole ring, showing that this is the strongest
binding. Other NH downfield shifts were Dd ¼ 1.10 ppm
for inner amides and Dd ¼ 1.29 ppm for outer butyl amide
groups. In addition, the two broad signals of pyrrole
protons were downfield shifted by Dd ¼ 0.15 ppm
collapsing in a sharp singlet and two aromatic protons
by Dd ¼ 0.10 ppm. No other changes for dansyl group or
benzylic protons signals were appreciated.
of increasing amounts of the guests but no significant
changes in the absorption spectra were observed. As
shown in Figures 5 and 6, the maxima of the excitation and
emission wavelengths are nearly invariant when dicarbox-
ylate concentrations were changed and only the intensity
of fluorescence was affected. These results can be
explained on the basis of a PET mechanism (32, 42–47),
because when a PET mechanism is involved in the sensing,
the absence of changes in the absorption spectra during the
association process is a requirement. This invariant
wavelength absorption maximum is that at which the
fluorescence spectra are measured.
2.3 Fluorescence studies
No fluorescence quenching of 1 was caused by the
interaction of the dicarboxylates with the dansyl group as
no changes were observed when a control experiment was
performed using methyl dansyl ester (c ¼ 1.7 £ 1025 M)
and the added anion; indeed, hydrogen bonding between
the bis-2,5-diamidopyrrole-based receptor and the dicar-
boxylate anions is responsible for the attenuation of the
fluorescence.
Receptor 1 showed an absorption spectrum with a lmax at
357 nm, c ¼ 1.7 £ 1025 M in chloroform–4% DMSO
solution, at 293 K. No significant changes were observed
in absorption spectra upon addition of the diTBA salts of
glutarate or adipate (0–10 equiv.; Figure 5). Significant
quenching of emission bands was observed upon addition
On the other hand, no changes of fluorescence were
found when the same experiment was carried out with
Figure 5. Absorption spectra (lexc ¼ 357 nm) of the free
receptor 1 (c ¼ 1.7 £ 1025 M) upon gradual addition of diTBA
glutarate in CHCl3–4% DMSO.
Figure 6. Quenching of fluorescence emission intensity
(lexc ¼ 357 nm) of receptor 1(c ¼ 1.7 £ 1025 M) upon addition
of diTBA glutarate in CHCl3–4% DMSO.

Supramolecular Chemistry
365
TetraButylAmmonium (TBA) acetate, confirming the
requirement of a bidentate complex for the fluorescence
quenching.
4.2 Synthesis
4.2.1 Methyl 5-(butylcarbamoyl)-1H-pyrrole-2-
carboxylate (5)
The addition of up to 3 equiv. of diTBA glutarate to a
solution of 1 (c ¼ 5.2 £ 1025 M) produces a progressive
quenching of the fluorescence intensity (70%), which is a
better response (at least 20% larger) than that observed
with receptor 2, as expected, because 1 sets two additional
hydrogen bonds in the complex. When diTBA adipate was
used as guest (see Supplementary Information, available
online), practically the same fluorescence response was
obtained, which is not surprising given the slight
Compound 5-(methoxycarbonyl)pyrrole-2-carboxylic acid
(4; 1.3 g, 7.7 mmol), prepared according to the literature
procedure (23), was refluxed in thionyl chloride (30 ml)
until the acid was completely dissolved and there were no
hydrogen chloride bubbles. The excess of thionyl chloride
was removed under high vacuum. The resulting acyl
chloride was dissolved in butylamine (25 ml, 18.5 g,
150 mmol) at 308C, and the mixture was stirred for
30 min at room temperature. The solvent was removed in
vacuo to yield compound 5 (1.8 g, 97%). Mp: 250–2518C.
1H NMR (CDCl3) d: 10.03 (1H, broad s, NH pyrrole), 6.86
(1H, d, J ¼ 4.0 Hz, H-3 pyrrole), 6.52 (1H, d, J ¼ 4.0 Hz,
H-4 pyrrole), 6.12 (1H, broad s, NH amide), 3.86 (3H, s, –
COOCH3), 3.4 (2H, c, J ¼ 6.6 Hz, CH2NHCO), 1.60–1.31
1
difference in Kass obtained by H NMR.
3. Conclusions
The receptor 1 described here with two bis-amidopyrrole
units shows interesting hydrogen bond interactions with
dicarboxylate anions, in both CDCl3–4% DMSO and
DMSO. Receptor 1 is capable of forming strong 1:1
complexes in the highly competitive DMSO solvent with
glutarate and adipate guests due to the formation of six
hydrogen bonds. A preference for glutarate over adipate
was shown. Also, the quenching of the fluorescence of
receptor 1 during the recognition event allows its potential
application as a sensor for these dicarboxylates (Figure 6).
(4H, m, CH2CH2), 0.93 (3H, t, J ¼ 7.0 Hz, CH3) ppm. 13
C
NMR (CDCl3) d: 161.0 (s), 160.4 (s), 130.0 (s), 124.8 (s),
115.5 (d), 110.6 (d), 51.6 (c), 39.4 (t), 31.6 (t), 20.0 (t), 13.5
(c) ppm. HRMS–ESI: (M þ Hþ) calcd for C11H17N2O3:
225.1234; found: 225.1241. IR (Nujol) (cm21): 3351, 1717,
1623, 1560, 1278, 1260, 1206, 1153, 1045, 936, 729.
4.2.2 5-(butylcarbamoyl)-1H-pyrrole-2-carboxylicacid(6)
Ester 5 (1.8 g, 7.5 mmol) was refluxed for 20 min in 50 ml of
an aqueous solution of NaOH. The reaction mixture was
acidified with concentrated HCl, and the precipitate was
4. Experimental section
1
4.1 General procedures
filtered off to give 6 (1.6 g, 94%). Mp: 260–2628C. H
NMR (400 MHz, DMSO-d6) d: 12.71 (1H, broad s, COOH),
11.91 (1H, broad s, NH pyrrole), 8.32 (1H, t, J ¼ 5.9 Hz,
NH amide), 6.71 (2H, broad s, H-3 and H-4 pyrrole), 3.20
(2H, c, J ¼ 6.4 Hz, CH2NHCO), 1.53–1.22 (4H, m,
CH2CH2), 0.88 (3H, t, J ¼ 7.1 Hz, CH3) ppm. 13C NMR
(DMSO-d6) d: 161.5 (s), 159.3 (s), 130.7 (s), 125.3 (s),
114.6 (d), 112.4 (d), 38.3 (t), 31.1 (t), 19.6 (t), 13.6 (c) ppm.
HRMS–ESI: (M þ Naþ) calcd. for C10H14N2O3Na
233.0897; found: 233.0914. IR (Nujol) (cm21): 3323,
3231, 1677, 1620, 1561, 1286, 1216, 1041, 928, 759.
Melting points were measured with a Stuart Scientific
SM3P capillary apparatus. IR spectra were recorded with a
Bonem MB-100FT IR spectrometer. NMR spectra were
recorded at room temperature with Bruker Mod. WP-200-
SY, Varian Mod. Mercury VS 2000 or Bruker Advance
DRX spectrometers in deuterated chloroform or dimethyl-
sulphoxide. J values are reported in hertzs and chemical
shifts in parts per million with the solvent signal as internal
standard. ESI–HRMS were recorded on an Applied
Biosystems QSTAR XL spectrometer. Fluorescence
measurements were carried out with a Shimadzu RF-
5301 PC fluorescence spectrometer. Stock solution of host
(1.7 £ 1024 M) was prepared in CHCl3–4% DMSO. Stock
solutions of ditetrabutylammonium salts of guests in
CHCl3 (1.7 £ 1023 M) were used. Test solutions were
prepared by adding 500 ml of host stock solution and
different volumes (25–500 ml) of the anion solution to a
series of test tubes followed by dilutions to 5 ml with
CHCl3. The solutions were excited at 357 nm and the
emission was measured between 425 and 675 nm.
4.2.3 2,5-dioxopyrrolidin-1-yl 5-(butylcarbamoyl)-1H-
pyrrole-2-carboxylate (7)
A solution of 6 (1.6 g, 7.1 mmol), N-(3-dimethyl
aminopropyl)-N0-ethylcarbodiimide hydrochloride (2.0 g,
10.6 mmol) and N-hydroxysuccinimide (1.2 g, 10.6 mmol)
in dry dichloromethane (50 ml) was stirred for 3 h at room
temperature under Ar atmosphere. The reaction mixture
was washed with water, dried with Na2SO4 and evaporated
affording intermediate 7 (2.0 g, 92%). Mp: 266–2678C. 1H
NMR (CDCl3) d: 10.36 (1H, broad s, NH pyrrole), 7.12
(1H, d, J ¼ 4.0 Hz, H-3 pyrrole), 6.59 (1H, d, J ¼ 4.0 Hz,
H-4 pyrrole), 6.25 (1H, t, J ¼ 6.1 Hz, NH amide) 3.42 (2H,
The binding stoichiometry of the complexes has been
determined by Job plots. Reagents were purchased at the
highest commercial quality and used without further
purification unless otherwise noted.

´
M.B. Jimenez et al.
366
c, J ¼ 6.1 Hz, NHZCH2), 2.88 (4H, s, succinimide),
1.65–1.29 (4H, m, CH2CH2), 0.93 (3H, t, J ¼ 7.1 Hz,
CH3) ppm. 13C NMR (CDCl3) d: 169.1 (s), 159.2 (s), 155.5
(s), 133.5 (s), 118.4 (s), 118.1 (d), 113.1 (d), 38.9 (t), 31.0
(t), 25.3 (t), 19.7 (t), 13.4 (c) ppm. HRMS–ESI: (M þ Hþ)
calcd for C14H18N3O5: 308.1241; found: 308.1254. IR
(Nujol) (cm21): 3349, 1768, 1738, 1668, 1618, 1560,
1280, 1174, 1051, 995, 835.
added to an ice-cooled solution of diol 12 (23.0 g,
85.7 mmol), phthalimide (38.6 g, 257.1 mmol) and triphe-
nylphosphine (67.4 g, 257.1 mmol) in THF (650 ml), and
the solution was stirred overnight at room temperature.
The solvent was then removed in vacuo affording a crude
reaction product as a yellow oil. Ethanol (400 ml) was then
added, and the mixture was stirred until a white solid
precipitated. The precipitate was filtered off and it was
identified as the diphthalimide derivative 13 (35 g, 78%).
Mp: 155–1568C. 1H NMR (CDCl3) d: 7.84 (4H, dd,
J1 ¼ 5.5 Hz, J2 ¼ 3.0 Hz, phthalimide), 7.70 (4H, dd,
J1 ¼ 5.5 Hz, J2 ¼ 3.0 Hz, phthalimide), 7. 07 (1H, s, Ar),
6.79 (2H, s, Ar), 4.74 (4H, s, 2CH2 benzylic), 0.89 (9H, s,
3CH3 TBDMS), 0.13 (6H, s, 2CH3 TBDMS) ppm. 13C
NMR (CDCl3) d: 167.8 (s), 156.1 (s), 138.0 (s), 133.9 (d),
132.1 (s), 123.2 (d), 121.3 (d), 119.3 (d), 41.2 (t), 25.6 (d),
18.1 (s), 24.5 (c) ppm. HRMS–ESI: (M þ Naþ) calcd for
C30H30N2O5NaSi: 549.1816; found: 549.1818. IR (Nujol)
(cm21): 2954, 2854, 1167, 1716, 1596, 1429, 1391,
1340, 1323, 1254, 1166, 1102, 1026, 938, 871, 837, 774,
733, 708.
4.2.4 Synthesis of intermediate dimethanamine (8)
4.2.4.1 Dimethyl 5-(tert-butyldimethylsilyloxy)isophtha-
late (11). A solution of dimethyl 5-hydroxyisophthalate
(10) (20.0 g, 95.0 mmol), tert-butyldimethylsilyl chloride
(21.0 g, 142.5 mmol) and imidazole (20.2 g, 297.0 mmol) in
DMF (200 ml) was stirred at room temperature under Ar
atmosphere for 18 h. Then, the reaction mixture was diluted
with ether (250 ml), washed with water, dried over Na2SO4
and the solvent was removed under reduced pressure to
yield the protected derivative 11 (30.0 g, 97%). Mp: 152–
1548C. 1H NMR (CDCl3) d: 8.28 (1H, s, Ar), 7.67 (2H, s,
Ar), 3.93 (6H, s, 2-COOCH3), 0.99 (9H, s, 3CH3 TBDMS),
0.23 (6H, s, 2CH3 TBDMS) ppm. 13C NMR (CDCl3) d:
166.0 (s), 155.9 (s), 131.9 (s), 125.3 (d), 123.6 (d), 52.2 (c),
25.5 (c), 18.1 (s), 24.5 (c) ppm. HRMS–ESI: (M þ Naþ)
calcd for C16H24O5NaSi: 347.1285; found: 347.1280. IR
(Nujol) (cm21): 2954, 2854, 1731, 1596, 1336, 1236, 1110,
1024, 939, 896, 837, 783, 756, 669.
4.2.4.4 (5-(tert-butyldimethylsilyloxy)-1,3-phenylene)di-
methanamine (8). Diphthalimide intermediate 13 (5.0 g,
9.5 mmol) was treated with hydrazine monohydrate
(1.2 ml, 1.2 g, 24.7 mmol) in ethanol (180 ml) under reflux
for 2 h, and appeared as a precipitate of phthalhydrazide.
Then the precipitate was filtered off, and the ethanol was
removed in vacuo. The residue was partitioned in
chloroform (100 ml) and water (100 ml), and the organic
layer was dried over Na2SO4 and evaporated to give 8
(1.4 g, 56%) as a yellow oil. 1H NMR (CDCl3) d: 6.87 (1H,
s, Ar), 6.67 (2H, s, Ar), 3.80 (4H, s, 2CH2 benzylic), 1.51
(4H, broad s, ZNH2), 0.99 (9H, s, 3CH3 TBDMS), 0.20
(6H, s, 2CH3 TBDMS) ppm. 13C NMR (CDCl3–4%
DMSO-d6) d: 154.8 (s), 144.1 (s), 117.7 (d), 115.8 (d),
45.2 (t), 24. 7 (c), 17.1 (s), 25.4 (c) ppm. HRMS–ESI:
(M þ Hþ) calcd for C14H27N2OSi: 267.1872; found:
267.1890. IR (Nujol) (cm21): 3420, 1600, 1350, 1280,
1150, 1045, 1000, 943, 890, 835, 730, 675.
4.2.4.2 (5-(tert-butyldimethylsilyloxy)-1,3-phenylene)di-
methanol (12). To a suspension of LiAlH4 (5.3 g,
139.0 mmol) in dry ether (150 ml), a solution of diester
11 (30.0 g 92.5 mmol) in dry ether (100 ml) was added.
The mixture was refluxed for 2 h and allowed to reach the
room temperature. H2O (6.3 ml), 15% NaOH (6.3 ml) and
H2O (18.9 ml) were successively added. The mixture was
stirred at room temperature for 5 min and filtered. The
filtrate was dried over Na2SO4 and evaporated to afford 12
(23.5 g, 95%) as a white solid, Mp: 145–1478C. 1H NMR
(CDCl3) d: 6.95 (1H, s, Ar), 6.77 (2H, s, Ar), 4.64 (4H, d,
J ¼ 6.0 Hz, 2CH2 benzylic), 1.67 (2H, t, J ¼ 6.0 Hz,
ZOH), 0.99 (9H, s, 3 £ CH3 TBDMS), 0.20 (6H, s,
2 £ CH3 TBDMS) ppm. 13C NMR (CDCl3) d: 155.7 (s),
142.7 (s), 118.2 (d), 117.5 (d), 64.5 (t), 25.7 (c), 18.1 (s),
24.4 (c) ppm. HRMS–ESI: (M þ Na þ ) calcd for
C14H24O3NaSi: 291.1387; found: 291.1386. IR (Nujol)
(cm21): 3241, 1595, 1320, 1293, 1251, 1151, 1058, 1009,
934, 887, 838, 782, 678.
4.2.4.5 N2,N20-(5-(tert-butyldimethylsilyloxy)-1,3-phe-
nylene) bis(methylene)bis(N5-butyl-1H-pyrrole-2,5-dicar-
boxamide) (9). A solution of diamine 8 (585 mg,
2.2 mmol), compound 7 (1.5 g, 4.9 mmol) and 4-DMAP
(61 mg, 0.5 mmol) in dry dichloromethane (30 ml) was
stirred at room temperature for 19 h under Ar atmosphere.
Compound 9 appeared as a precipitate that was filtered
1
off (900 mg, 64%). Mp . 1608C H NMR (DMSO-d6) d:
4.2.4.3 2,20-(5-(tert-butyldimethylsilyloxy)-1,3-phenyle-
ne)bis(methylene)diisoindoline-1,3-dione (13). A solution
of 50.6 ml (52.0 g, 257.1 mmol) of DIAD was slowly
11.72 (2H, broad s, NH pyrrole), 8.79 (2H, t, J ¼ 5.7 Hz,
inner NH amide), 8.23 (2H, t, J ¼ 5.8 Hz, outer NH
amide), 6.84 (1H, s, Ar), 6.80 (2H, s, Ar), 6.74 (4H, m, H-

Supramolecular Chemistry
8 and H-9 pyrrole), 4.35 (4H, d, 2CH2 benzylic), 3.20 4.3 X-ray crystallographic study
367
(4H, c, J ¼ 5.8 Hz, NHZCH2), 1.53–1.21 (8H, m,
CH2CH2), 0.89 (6H, t, J ¼ 7.1 Hz, CH3), 0.89 (9H, s,
3CH3 TBDMS), 0.12 (6H, s, 2CH3 TBDMS) ppm. 13C
NMR (DMSO-d6) d: 159.4 (s), 159.2 (s), 154.7 (s), 140.8
(s), 128.6 (s), 128.0 (s), 119.0 (d), 116.7 (d), 111.0 (d),
41.5 (t), 37.8 (t), 30.7 (t), 25.1 (c), 19.1 (t), 17.3 (s), 13.2
(c), 25.0 (c) ppm. HRMS–ESI: (M þ Naþ) calcd for
C34H50N6O5NaSi: 673.3504; found: 673.3486. IR (Nujol)
(cm21): 3237, 1617, 1530, 1299, 1154, 1023, 838, 764.
Suitable single crystals of compounds 2 and 3 were
mounted on glass fibre for data collection on a Bruker
Kappa APEX II CCD diffractometer. Data were collected
˚
at 298 K using CuZKa radiation (l ¼ 1.54178 A) and v
scan technique, and were corrected for Lorentz and
polarisation effects. Structure solution, refinement and
data output were carried out with the SHELXTLTM
programme package. The structures were solved by direct
methods combined with difference Fourier synthesis and
refined by full-matrix least-square procedures, with
anisotropic thermal parameters in the last cycles of
refinement for all non-hydrogen atoms. It should be noted
that some hydrogen atoms from the solvent molecules are
shown in the structural formula of the complexes, though
they were not located by X-ray diffraction.
4.2.5 3,5-bis((5-(butylcarbamoyl)-1H-pyrrole-2-
carboxamido) methyl)phenyl 5-(dimethylamino)naphthalene-
1-sulfonate (Receptor 1)
To a solution of compound 9 (700 mg, 1.1 mmol) and
dansyl chloride (355 mg, 1.3 mmol) in dichloromethane
(20 ml) and THF (20 ml), TBAF 1 M in THF (4.4 ml,
4.4 mmol) was added. The reaction mixture was stirred for
3 h. Then the solvent was evaporated, and the residue was
dissolved in dichloromethane and washed with water
(3 £ 20 ml). In the organic layer, a precipitate appeared,
which was filtered off and was identified as pure receptor 1
(825 mg, 74%).
Mp . 1658C 1H NMR (DMSO-d6) d: 11.67 (2H,
broad s, NH pyrrole), 8.74 (2H, t, J ¼ 2.0 Hz, inner NH
amide), 8.41 (1H, d, J ¼ 8.0 Hz, dansyl), 8.24 (2H, t,
J ¼ 2.0 Hz, outer NH amide), 8.17 (1H, d, J ¼ 8.4 Hz,
dansyl), 8.05 (1H, d, J ¼ 8.0 Hz, dansyl), 7.63 (1H, t,
J ¼ 8.4 Hz, dansyl), 7.42 (1H, t, J ¼ 8.0 Hz, dansyl), 7.19
(1H, d, J ¼ 8.4 Hz, dansyl), 7.15 (1H, s, Ar), 6.77 (2H, s,
Ar), 6.75 (2H, broad s, H-8 pyrrole), 6.71 (2H, broad s, H-9
pyrrole), 4.31 (4H, d, J ¼ 5.3 Hz, 2CH2 benzylic), 3.23
(4H, c, J ¼ 5.9 Hz), 2.79 (6H, s, 2CH3 dansyl) 1.48 (4H,
m, CH2CH2), 1.31 (4H, m, CH2CH2), 0.89 (6H, t,
J ¼ 7.1 Hz, CH3) ppm. 13C NMR (DMSO-d6) d: 159.7 (s),
159.6 (s), 151.7 (s), 149.3 (s), 142.1 (s), 132.0 (d), 130.8
(d), 130.2 (s), 129.3 (s), 129.1 (d), 129.0 (s), 128.8 (s),
128.1 (s), 125.0 (d), 123.3 (d), 118.4 (d), 117.9 (d), 115.5
(d), 111.6 (d), 111.5 (d), 44.9 (c), 41.4 (t), 38.3 (t), 31.2 (t),
19.6 (t), 13.7 (c) ppm. HRMS–ESI: (M þ Naþ) calcd for
C40H47N7O7NaS: 792.3150; found: 792.3128. IR (Nujol)
(cm21): 3279, 1612, 1553, 1450, 1294, 1183, 976,
814, 749.
(a) Crystal data for 2: C30H29N5O5S £ C4H8O,
M ¼ 643.75, monoclinic, space group P21/c (n8 14),
˚
˚
a ¼ 15.311(3)A, b ¼ 19.925(4) A, c ¼ 11.024(2),
3
˚
a ¼ g ¼ 908, b ¼ 103.87(3), V ¼ 3265.1(11) A ,
Z ¼ 4, Dc ¼ 1.310 mg/m3, m ¼ (Cu 2 Ka) ¼ 1.316
mm21, F(000) ¼ 1360. 4984 reflections were col-
lected at 2.97 # 2u # 60.01 and merged to give 4796
unique reflections (Rint ¼ 0.0439), of which 2965
with I . 2 s (I) were considered to be observed. Final
values are R1 ¼ 0.0541, wR2 ¼ 0.1220, GOF ¼ 0.923
max/min residual electron density 0.333 and
23
˚
20.391 e A
.
(b) Crystal data for 3: C31H25N5O3 £ C2H6OS,
M ¼ 593.70, monoclinic, space group P21/c (n8 14),
˚
˚
˚
a ¼ 9.8461(4) A, b ¼ 36.6555(14) A, c ¼ 8.3854(4) A,
3
˚
a ¼ b ¼ g, b ¼ 99.925(2)8, V ¼ 2981.1(2) A , Z ¼ 4,
Dc ¼ 1.323 mg/m3, m ¼ (Cu 2 Ka) ¼ 1.347 mm21
,
F(000) ¼ 1248. 6159 reflections were collected at
2.41 # 2u # 45.98 and merged to give 2527 unique
reflections (Rint ¼ 0.0227), of which 1885 with I . 2 s
(I) were considered to be observed. Final values are
R1 ¼ 0.0665, wR2 ¼ 0.1730, GOF ¼ 1.039, max/min
23
.
˚
residual electron density 1.261 and 20.338 e A
Crystallographic data (excluding structure factors) for
the structures reported in this paper have been deposited at
the Cambridge Crystallographic Data Centre as Sup-
plementary Information, available online n8. CCDC
829184 – 829185.
4.2.6 Tetrabutylammonium salts
Acknowledgements
´
We thank the Junta de Castilla y Leon (Grant SA125 A06) and
´
the Spanish Ministerio de Ciencia e Innovacion (CTQ2008-
01771) for supporting the research reported in this article. M.B. J.
Tetrabutylammonium salts were prepared by adding
2 equiv. of tetrabutylammonium hydroxide in methanol to
a solution of the corresponding dicarboxylic acid (1 equiv.)
in methanol. The mixture was stirred at room temperature
for 2 h and evaporated to dryness under reduced pressure
and then dried under a high vacuum.
´
thanks the Junta de Castilla y Leon for a Ph.D. grant. The Spanish
Ministerio de Educacion is acknowledged by A. L. F. A. for a
´
´
FPU grant. We also thank M. Teresa Prior and Marina Gonzalez
for their help with fluorescence experiments.

´
M.B. Jimenez et al.
368
(23) Liu, S.-Y.; He, Y.-B.; Wu, J.-L.; Wei, L.-H.; Qing, H.-J.;
Meng, L.-Z.; Hu, L. Org. Biomol. Chem. 2004, 2,
1582–1586.
(24) Ghosh, K.; Masanta, G. Tetrahedron Lett. 2008, 49,
2592–2597.
(25) Qin, D.B.; Xu, F.B.; Wan, X.J.; Zhao, Y.J.; Zhang, Z.Z.
Tetrahedron Lett. 2006, 47, 5641–5643.
´
(26) Martinez-Man˜ez, R.; Sancenon, F. Chem. Rev. 2003, 103,
4419–4476.
(27) Mei, M.H.; Wu, S.K. New. J. Chem. 2001, 25, 471–475.
(28) Jimenez, M.B.; Calle, E.; Caballero, M.C. Sensors 2009, 9,
1534–1540.
(29) Gale, P.A. Chem. Commun. 2005, 30, 3761–3772.
(30) dos Santos, C.M.G.; Glynn, M.; MacCabe, T.; Seixas de
Melo, J.S.; Burrows, H.D.; Gunnlaugsson, T. Supramol.
Chem. 2008, 20, 407–418.
(31) de Silva, A.P.; Gunaratne, H.Q.N.; Gunnlaugsson, T.
Tetrahedron Lett. 1998, 39, 50–77.
(32) Nishizawa, S.; Kaneda, H.; Uchida, T.; Teramae, N.J.
Chem. Soc. Perkin Trans. 1998, 2, 2325–2327.
(33) Zhou, X.-B.; Yip, Y.-W.; Chan, W.-H.; Lee, A.W.M.
Beilstein J. Org. Chem. 2011, 7, 75–81.
References
(1) For more recent reviews, see: temed issue on Supramole-
cular Chemistry of Anionic Species, Ed. Gale, P.A.,
Gunnlaugsson, T. Chem. Soc. Rev. 2010, 39, 3581.
(2) Dydio, P.; Lichosyt, D.; Jurczak, J. Chem. Soc. Rev. 2011,
40, 2971–2985.
(3) Sessler, J.L.; Gale, P.A.; Cho, W.-S. Anion Receptor
Chemistry; Royal Society of Chemistry: Cambridge, UK,
2006.
(4) Juwarker, H.; Jeong, K.-S. Chem. Soc. Rev. 2010, 39,
3664–3674.
´
(5) Mun˜iz, F.M.; Alcazar, V.; Sanz, F.; Simon, L.; Fuentes de
Arriba, A.L.; Raposo, C.; Moran, J.R. Eur. J. Org. Chem.
´
´
2010, 6179–6185, and ref. therein.
´
´
´
´
(6) Gonzalez, S.; Pelaez, R.; Sanz, F.; Jimenez, M.B.; Moran,
J.R.; Caballero, M.C. Org. Lett. 2006, 8, 4679–4682.
(7) Gunnlaugsson, T.; Davis, A.P.; O’Brien, E.J.; Glynn,
M. Org. Biomol. Chem. 2005, 3, 48–56.
(8) Zeng, Z.-Y.; He, Y.-B.; Wu, J.-L.; Wei, L.-H.; Liu, X.;
Meng, L.-Z.; Yang, X. Eur. J. Org. Chem. 2004,
2888–2893.
(34) Barker, P.; Gendler, P.; Rapoport, H. J. Org. Chem. 1978,
43, 4849–4853.
(9) Ghosh, K.; Saha, I.; Masanta, G.; Wang, E.B.; Parish, C.A.
Tetrahedron Lett. 2010, 51, 343–347.
(35) Connors, K.A. Binding Constants; John Wiley & Sons: New
York, 1987; p 24.
(36) Fielding, L. Tetrahedron 2000, 56, 6151–6170.
(37) Blanda, M.T.; Horner, J.H.; Newcomb, M. J. Org. Chem.
1989, 54, 4626–4636.
(38) Scheneider, H.J.; Yatsimirsky, A.K. Principles and
Methods in Supramolecular Chemistry; John Wiley &
Sons: New York, 2000.
(39) Wilcox, C.S. In Frontiers in Supramolecular Organic
Chemistry and Photochemistry; Schneider, H.-J., Du¨rr, H.,
Eds.; VCH: Weinheim, 1991; pp 123–143.
(40) Thordarson, P. Chem. Soc. Rev. 2011, 40, 1305–1323.
(41) Sessler, J.M.; Gross, D.E.; Cho, W.-S.; Lynch, W.M.;
Schmidtchen, F.P.; Bates, G.W.; Light, M.E.; Gale, P.A.
J. Am. Chem. Soc. 2006, 128, 12281–12288.
(42) Veale, E.B.; Tocchi, M.G.; Pfeffer, F.M.; Kruger, P.E.;
Gunnlaugsson, T. Org. Biomol. Chem. 2009, 7, 3447–3454.
(43) Kang, J.; Kim, H.S.; Jang, D.O. Tetrahedron Lett. 2005, 46,
6079–6082.
(44) Gunnlaugsson, T.; Davis, A.P.; Hussey, G.M.; Tierney, J.;
Glynn, M. Org. Biomol. Chem. 2004, 2, 1856–1863.
(45) Kim, S.K.; Yoon, J. Chem. Commun. 2002, 7, 770–771.
(46) Gunnlaugsson, T.; Davis, A.P.; Glynn, M. Chem. Commun.
2001, 24, 2556–2557.
´
´
´
(10) Jimenez, M.B.; Alcazar, V.; Pelaez, R.; Sanz, F.; Fuentes de
Arriba, A L.; Caballero, M.C. Org. Biomol. Chem. 2012, 10,
1181–1185.
(11) Jane, D.E. In Medicinal Chemistry into the Millennium;
Campbell, M.M., Blagbrough, I.S., Eds.; Royal Society of
Chemistry: Cambridge, 2001; pp 67–84.
(12) Berg, M.; Tymoczko, J.L.; Stryer, L. Biochemistry; 5th ed.
Freeman: New York, 2002.
(13) Gross, D.E.; Mikkilineni, V.; Lynch, V.M.; Sessler, J.L.
Supramol. Chem. 2010, 22, 135–141.
(14) Sessler, J.L.; Pantos, G.D.; Gale, P.A.; Light, M.E. Org.
Lett. 2006, 8, 1593–1596.
(15) Suk, J.-M.; Kim, J.-I.; Jeong, K.-S. Chemistry Asian J.
2011, 6, 1992–1995.
(16) Chae, M.K.; Suk, J.-M.; Jeong, K.-S. Tetrahedron Lett.
2010, 51, 4240–4242.
(17) Zielinski, T.; Jurczak, J. Tetrahedron 2005, 61, 4081–4089.
(18) Gale, P.A. Chem. Commun. 2008, 4525–4540.
(19) Evans, L.S.; Gale, P.A.; Light, M.E.; Quesada, R. New.
J. Chem. 2006, 30, 1019–1025.
(20) Gale, P.A.; Camiolo, S.; Chapman, C.P.; Light, M.E.;
Hursthouse, M.B. Tetrahedron Lett. 2001, 42, 5095–5097.
(21) Ghosh, K.; Sarkar, A.R. Tetrahedron Lett. 2009, 50, 85–88.
(22) Ghosh, K.; Masanta, G.; Chattopadhyay, A.P. Eur. J. Org.
Chem. 2009, 26, 4515–4524.
(47) Gunnlaugsson, T.; Davis, A.P.; O’Brien, E.J.; Glynn, M.
Org. Lett. 2002, 4, 2449–2452.