Minimalist peptidomimetic cyclophanes as strong organogelators

Article abstract of DOI:10.1039/b111229e

L-Valine containing cyclophanes have been shown to gelate organic solvents leading to soft materials with a clear expression of their chirality at the supramolecular level.

Full text of DOI:10.1039/b111229e

Minimalist peptidomimetic cyclophanes as strong organogelators
Jorge Becerril, M. Isabel Burguete, Beatriu Escuder,* Santiago V. Luis,* Juan F. Miravet and Manel
Querol
Departament de Química Inorgànica i Orgànica, Universitat Jaume I, 12080 Castelló, Spain.
E-mail: escuder@qio.uji.es; Fax: +34-964-728214; Tel: +34-964-728239
Received (in Cambridge, UK) 12th December 2001, Accepted 20th February 2002
First published as an Advance Article on the web 5th March 2002
L-Valine containing cyclophanes have been shown to gelate
oxycarbonyl protected
L-valine was activated as the N-
organic solvents leading to soft materials with a clear
expression of their chirality at the supramolecular level.
hydroxysuccinimidyl ester and coupled with the corresponding
diamine. Deprotection of the amino groups led to compounds
2a–c that were converted into macrocycles 3a–c by coupling
with 1,3-bis(bromomethyl)benzene in CH3CN using K2CO3 as
a base.4
The design of systems capable of self-assembly into well-
defined organized architectures is a topic of intense research.
Among them, low molecular weight organic molecules have
been shown to be capable of trapping large amounts of solvent
resulting in the formation of strong gels constituted by fibrillar
supramolecular networks reversiblely assembled exclusively
via non covalent interactions.1
Here we report how the minimalist peptidomimetic cyclo-
phanes shown in Scheme 1 are able to gelate several organic
solvents leading to soft materials made of reversible fibrillar
structures, and how in some cases their molecular chirality is
further expressed at the supramolecular level. Several examples
of amino acid based organogelators, either linear or cyclic, have
been reported in the literature.2,3 However, to our knowledge,
compounds 3a–c are unique because of the ensemble of
structural simplicity and preorganization that makes them good
candidates for participating in self-assembling processes. One
of the key features of macrocyclic compounds in regard to their
participation in such processes is the increased preorganization
of their interaction sites with respect to the acyclic analogues.
This leads to more specific Van der Waals and H-bonding
interactions that in the case reported here most likely contribute
to the gelation process.
The gelation† behaviour of these small peptidomimetics was
studied in a variety of solvents and some results are gathered in
Table 1. As can be seen, these compounds are good organogela-
tors, specially for aromatic solvents, forming transparent gels
either by slow or fast cooling of their hot solutions (Fig. 1).
Scanning electron microscopy was used to study the
microscopic structure of the gels. In most cases, an extended
fibrillar network was observed (Fig. 2, top) but in some of them
helical architectures could also be detected. The electron
micrographs of the gel formed by compound 3a in benzene
revealed the presence of a mixture of isolated right-handed
twisted ribbons of several micrometers of length and pitch, as
well as cylindrical objects together with longer fibers (Fig. 2,
bottom). When the gel was formed by fast cooling of the hot
solution an increase in the number of helices was found together
with a decrease in their size. It is known that twisted ribbons are
often precursors in the growth of tubules.5 According to this, the
fast cooling could freeze the primitive helical states whereas
slow cooling lead to the formation of long rod-like fibers
Table 1 Gelation behaviour of 3a–c in various solventsa
The preparation of compounds 3a–c was carried out using
well known peptide synthetic methodology. Thus, the benzyl-
Solvent
3a
3b
3c
Benzene
Toluene
Xylene
0.3
0.5
0.5
0.5
0.5
0.5
P
S
S
S
S
0.5
P
P
—
0.5
0.5
P
S
S
S
S
0.3
0.4
1
0.5
0.3
0.5
P
0.5
S
S
Styrene
Anisole
Nitrobenzene
Acetone
THF
Isopropanol
n-Butanol
CH2Cl2
S
CHCl3
S
S
S
EtOAc
n-Hexane
1
NS
P
NS
0.1
NS
a Minimum gelator concentration, % wt; S: soluble; P: precipitated; NS: not
soluble.
Fig. 1 Gels formed by compound 3a in nitrobenzene (left), EtOAc (middle)
and benzene (right, the magnetic stirrer stands over the gel surface).
Scheme 1
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Fig. 3 1H NMR of compound 3a in benzene-d6 (0.5% wt) as a gel at 20 °C
(a), and in solution at 30 °C (b).
their long correlation times. Indeed, the molecules in the mobile
part of the gel showed an increase in the 1H NMR longitudinal
relaxation time (T1) when compared to solution, in agreement
with the slower motion within the gel. The gelation process was
also followed by IR spectroscopy which revealed an increase of
the associated N–H band together with a shift in the CNO
confirming the importance of H-bonding in the formation of the
gel. Thus, the gel fibers could be formed by an infinite network
of intermolecular H-bonds between the N–H and the carbonyl
groups.
In conclusion, we have shown how small molecules with the
required functional groups are able to organize themselves and
the bulk solvent into reversible supramolecular architectures
with a precise transcription of the molecular chirality at the
supramolecular level. Currently we are investigating in detail
the macroscopic and microscopic features of this family of
organogelating chiral cyclophanes and related compounds, and
envisaging future applications in the fields of molecular
recognition and catalysis.
This research was supported by the spanish CICYT grant
BQU2000-1424 and BANCAIXA P1.1A2000-10.
Notes and references
† Gelation procedure: the required amount of organogelator (3–10 mg) was
dissolved in hot solvent (1 mL) and the gel was formed by cooling in an ice
bath (fast cooling) or by standing at rt (slow cooling). Samples for SEM
were prepared by slow drying of the gel followed by gold–palladium
sputtering in a Polaron SC7610 Sputter Coater from Fisons Instruments.
Scanning electron micrographs were taken using a LEO 440I spectrometer
equipped with a digital camera.
Fig. 2 SEM pictures of the dried gels of 3c in EtOAc (top), and in
nitrobenzene (middle). Helices formed by 3a in benzene (bottom).
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together with a decrease in the number of helical aggregates
seen.
1H NMR studies were carried out for solutions of 0.5–0.3%
wt of compound 3a in benzene-d6 at different temperatures
between 50 °C and 15 °C. The formation of transparent gels
below ca. 22 °C was accompanied with the shift of the
resonances for the aromatic protons in positions 2 and 5 as well
as that of the amide signal (Fig. 3). When the spectra were
recorded in the presence of 1 µL of CH2Cl2 as internal standard
a decrease of ca. 25% of the relative intensity of the signals of
compound 3a was observed upon gel formation. This behaviour
could be explained, as reported before for other organogela-
tors,3 as a consequence of the lowering in the concentration of
the free gelator in the solution entrapped by the gel. The signals
of the gelator molecules assembled in the gel network most
likely broaden to the point of non-observability as a result of
CHEM. COMMUN., 2002, 738–739
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