Glycoluril-tetrathiafulvalene molecular clips: On the influence of electronic and spatial properties for binding neutral accepting guests

Article abstract of DOI:10.3762/bjoc.11.115

Glycoluril-based molecular clips incorporating tetrathiafulvalene (TTF) sidewalls have been synthesized through different strategies with the aim of investigating the effect of electrochemical and spatial properties for binding neutral accepting guests. W

Full text of DOI:10.3762/bjoc.11.115

Glycoluril–tetrathiafulvalene molecular clips: on the influence
of electronic and spatial properties for binding neutral
accepting guests
Yoann Cotelle, Marie Hardouin-Lerouge, Stéphanie Legoupy, Olivier Alévêque,
Eric Levillain* and Piétrick Hudhomme*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2015, 11, 1023–1036.
Université d'Angers, Laboratoire MOLTECH-Anjou, CNRS UMR 6200,
2 Boulevard Lavoisier, F-49045 Angers, France
doi:10.3762/bjoc.11.115
Received: 13 March 2015
Accepted: 28 May 2015
Published: 17 June 2015
Email:
Eric Levillain* - eric.levillain@univ-angers.fr;
Piétrick Hudhomme* - pietrick.hudhomme@univ-angers.fr
This article is part of the Thematic Series "Tetrathiafulvalene chemistry".
Guest Editor: P. J. Skabara
* Corresponding author
Keywords:
donor–acceptor interactions; glycoluril; molecular clips;
supramolecular chemistry; tetrathiafulvalene
© 2015 Cotelle et al; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
Glycoluril-based molecular clips incorporating tetrathiafulvalene (TTF) sidewalls have been synthesized through different strate-
gies with the aim of investigating the effect of electrochemical and spatial properties for binding neutral accepting guests. We have
in particular focused our study on the spacer extension in order to tune the intramolecular TTF···TTF distance within the clip and,
consequently, the redox behavior of the receptor. Carried out at different concentrations in solution, electrochemical and spectro-
electrochemical experiments provide evidence of mixed-valence and/or π-dimer intermolecular interactions between TTF units
from two closed clips. The stepwise oxidation of each molecular clip involves an electrochemical mechanism with three one-elec-
tron processes and two charge-coupled chemical reactions, a scheme which is supported by electrochemical simulations. The fine-
tunable π-donating ability of the TTF units and the cavity size allow to control binding interaction towards a strong electron
acceptor such as tetrafluorotetracyanoquinodimethane (F4-TCNQ) or a weaker electron acceptor such as 1,3-dinitrobenzene
(m-DNB).
Introduction
Thanks to its remarkable redox properties and strong π-donating science [2-5]. In addition to the well-known access to molecu-
character demonstrated with the pioneering work of F. Wudl in lar conductors [6,7] and TTF-acceptor assemblies [8,9], new
the early 1970s [1], tetrathiafulvalene (TTF) has become one of concepts have been explored in the field of supramolecular
the most popular electroactive frameworks used in materials chemistry using the TTF unit as a powerful electroactive
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building block [10]. Exploiting its peculiar electronic (two principle have been synthesized in order to use them for recog-
successive reversible oxidation steps giving rise to three stable nition of aromatic guest molecules through π–π interactions
redox states) characteristics, more and more sophisticated TTF- [16,17].
based supramolecular systems have been designed, being able
to operate as machines, chemical sensors, redox-switchable We recently described various glycoluril-based molecular clips
ligands, molecular shuttles, molecular switches and logic gates 1–4 [18,19] (Figure 1) for which the structure varies by: i) the
[11]. Considering that molecular receptors prone to specifically nature of connection between the glycoluril spacer and the TTF
recognize neutral molecules through donor–accceptor interac- sidewalls, ii) the nature of the peripheral substituents on both
tions are of particular interest [12], the unique π-donating ability TTF pincers. In this full research paper we propose to study
and the planar geometry of the TTF building-block are suited to how these structural parameters influence the electron donating
the construction of such receptors. Nevertheless, the incorpor- ability of TTF pincers and the size of the cavity and how the
ation of TTF as a π-donating element in molecular clips or control over the inter-TTFs distance within the molecular clip
tweezers for recognition of neutral electron acceptor guests is impacts the ability for sandwiching neutral acceptor guests.
still relatively unexplored [13].
Those studies are supported by electrochemical analyses
(including simulation), time-resolved spectroelectrochemical
Molecular clips and tweezers can be defined as receptors experiments and UV–visible titrations.
presenting an open cavity composed of two interaction sites
Results and Discussion
which are separated by a spacer [13-15]. Ideally, these systems
are designed with the aim of sandwiching a molecular guest Synthesis
with a high degree of selectivity and control of the interactions We have designed molecular clips 1–4 through three different
between the guest and the sidewalls. While the nature and the synthetic strategies starting from diphenylglycoluril 5
flexibility of the spacer between the two sidewalls play a criti- (Scheme 1). The key building-block 5 is available in multigram
cal role in the recognition process, we were interested in rigidi- scale by reaction of benzil with urea [20]. The first approach
fying the molecular clips in order to favor the “lock and key” leading to molecular clips 1 and 2 is based on a straightforward
model [15]. This rigid structure offers the possibility to orient double nucleophilic substitution leading to a seven-membered
the interaction sites in a defined manner allowing an increase of ring using 4,5-bis(bromomethyl)-2-thioxo-1,3-dithiole (6) [21].
the binding strength with the guest. In the last two decades,
glycoluril-based molecular clips have shown that they were In order to determine the optimized experimental procedure to
capable of acting as excellent receptors by exploiting the dis- carry out the urea N-alkylation of compound 5, we took advan-
tance between the two aromatic sidewalls which is usually close tage from literature of previous works realized on glycoluril for
to 7 Å. Since then, a large number of host systems based on this such reaction using a 2,3-bis(halogenomethyl)aryl derivative.
Figure 1: Structures of molecular clips 1–4.
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Scheme 1: Different routes developed for the synthesis of molecular clips 1–4.
Reported procedures were using KOH [22,23], t-BuOK [24-26] between diphenylglycoluril 5 and 4,5-bis(bromomethyl)-2-
or NaH [27] as the base with DMSO as an aprotic polar solvent. thioxo-1,3-dithiole (6) as the electrophilic reagent (Scheme 2)
Different experimental conditions were tested for the reaction by varying parameters such as the nature of the base, the reac-
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Beilstein J. Org. Chem. 2015, 11, 1023–1036.
Scheme 2: Reaction between diphenylglycoluril with 4,5-bis(bromomethyl)-2-thioxo-1,3-dithiole.
tion time and the temperature (Table 1). Optimal conditions step, the introduction of the naphthoquinone spacer in clip 4
were using four equivalents of t-BuOK in anhydrous DMSO by required the previous transformation of compound 5 into a
keeping the temperature at 20 °C with a cryostat apparatus for glycoluril-based framework possessing quinone moieties for
3 h. Compound 7 was isolated in 36% yield after purification by developing a Diels–Alder cycloaddition strategy. Thus com-
silica gel chromatography. We should note that an increase of pound 12 [33] was prepared in 73% yield by treatment with
temperature resulted in the degradation of starting material 6.
an excess of hydroquinone in 1,2-dichloroethane using a
Friedel–Crafts alkylation as an electrophilic aromatic substitu-
tion onto compound 11 [34]. The hydroquinone moieties were
subjected to a dehydrogenation reaction using DDQ in THF to
reach desired glycolurildiquinone 13 [35] in 91% yield. The
Diels–Alder cycloaddition was carried out by treatment of bis-
dienophile 13 with TTF derivative 14 [36], able to give rise in
situ to the transient diene by reductive elimination using naked
iodide [37-39] or the iodo-ionic liquid 1-butyl-3-methylimida-
zolium iodide [40]. After purification by column chromatog-
raphy on silica gel, we noted that complete aromatization has
occurred concomitantly and molecular clip 4 was isolated in
around 20% yield.
Table 1: Optimized experimental conditions for the synthesis of com-
pound 7.
Base
Temperature (T) Reaction time (t)
Yield [%]
KOH
NaH
rt
rt
rt
rt
24 h
24 h
4 h
6
5
KOH
12
19
12
36
t-BuOK
4 h
t-BuOK Controlled 30 °C
t-BuOK Controlled 20 °C
4 h
3 h
This first strategy to reach clips 1 and 2 was considering the Whereas all attempts at growing crystals of molecular clips 1
trimethylphosphite-mediated cross-coupling reaction involving and 4 of sufficient quality for X-ray analysis have been unsuc-
2-oxo-1,3-dithiole moiety 8 [28] as an efficient route to prepare cessful so far, suitable single crystals were obtained by slow
dissymmetrical TTF derivatives [29]. The polarity of com- diffusion from a solution of clips 2 and 3 in a CH2Cl2/hexane
pounds which were formed was sufficiently different to allow mixture. Considering the central double bond of each TTF
an efficient purification by silica gel chromatography affording moiety, the intramolecular wall-to-wall distance was deter-
molecular clip 1 in 15% yield. This route was successfully mined to be equal to 8.25 Å and 7.41 Å for clip 2 and 3, res-
applied using compound 9 [30] and clip 2 was also isolated in pectively (Figure 2) [18]. Then the corresponding wall-to-wall
15% yield. Target clip 3 was finally obtained in 72% yield by distance between the two TTF units was determined by theoreti-
deprotection of precursor 2 using CsOH·H2O in DMF/MeOH cal calculations using the semi-empirical AM1 method in the
mixture [31], followed by the tetraalkylation of tetrathiolate case of 4 [19]. This distance was estimated to be equal to 9.7 Å
with iodomethane. Considering that this multi-step synthesis indicating that this enlargement around 2 Å was the result
was affording molecular clip 3 in an overall 4% yield starting mainly of the spatial contribution of the additional naphtho-
from diphenylglycoluril 5, we took advantage of the accessi- quinone spacer in molecular clip 4.
bility of 2,3-bis(bromomethyl)TTF 10 [32] bearing methylsul-
fanyl groups to investigate a more straightforward strategy. Electrochemical properties
Alternatively, the above methodology described for the prepar- The electrochemical behaviour of molecular clips 1–4 were
ation of compound 7 was efficiently applied to reach molecular determined using cyclic voltammetry experiments (Table 2).
clip 2 in 48% yield using similar experimental conditions.
These studies displayed a different electrochemical behavior for
Whereas the synthesis of molecular clips 1, 2 and 3 uses the clips 1, 2 and 3 in comparison to clip 4. In the latter case, the
nucleophilic substitution onto diphenylglycoluril 5 as a key- cyclic voltammogram (CV) showed two oxidation waves at
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Figure 2: Intramolecular distances between TTF moieties from X-ray analysis for clips 2 and 3 and theoretical calculations for clip 4.
tweezers based on a 1,2,4,5-tetramethylbenzene scaffold
[42,43].
Table 2: Apparent redox potentials of molecular clips 1, 2, 3 and 4
reported vs Fc+/Fc in 0.1 M TBAPF6/CH2Cl2/CH3CN 3:1 on glassy
carbon electrode at 100 mV·s−1. Absolute errors on potentials were
found to be around +/−10 mV.
At this stage, one should keep in mind that the distance between
two TTF sidewalls within clips 2 and 3 is quite important (8.2 Å
and 7.4 Å, respectively). Such a distance, even though deter-
mined in the solid state, does not seem compatible to allow an
intramolecular interaction to occur between two TTF units
during the first oxidation step. In order to address this issue and
to explore possible intermolecular (between two clips) interac-
tions, concentration dependence electrochemical experiments
were performed. Cyclic voltammograms were recorded using
molecular clip 2 at different concentrations (10−3 M, 10−4 M
and 5 × 10−5 M) (Figure 4).
Clip
Eapp0red1
Eapp0ox1
Eapp0ox1’
Eapp0ox2
1
2
3
4
–
–
+0.06
+0.03
−0.05
+0.21
+0.14
+0.06
+0.51
+0.45
+0.36
+0.65
–
−1.05
+0.28
Eapp0ox1 = +0.28 V and Eapp0ox2 = +0.65 V vs Fc+/Fc corres-
ponding to the successive generation of cation radical then dica-
tion species simultaneously on each TTF framework (Figure 3).
This unique first two-electron oxidation step indicates that the
two TTF units are electrochemically equivalent, thus excluding
the presence of intra- or intermolecular electronic interactions
between them. It should be noted that the electroactive naphtho-
quinone acceptor group incorporated in the spacer unit is char-
acterized by a reduction wave (Eapp0red1) at −1.05 V vs Fc+/Fc.
On the contrary, the CV of clips 1–3 shows a significant split-
ting of the first oxidation wave (Eapp0ox1 and Eapp0ox1’),
suggesting the presence of intermolecular (between two clips)
or intramolecular (within a clip) interactions between two TTF
units (i.e., mixed valence and/or π-dimer) [41]. Eventually, the
reversible two-electron process (i.e., 1 e− on each TTF+· unit)
for the second oxidation step (Eapp0ox2) leading to fully
oxidized TTF units is in accordance with independent TTF2+
states subject to repulsive electrostatic interactions. Such split-
ting phenomenon of the first oxidation wave has been previ-
ously reported by Azov et al. for TTF-containing molecular
Importantly, whereas the splitting of the first oxidation wave
was perfectly observed at high concentration (10−3 M), we
noted that the phenomenon was significantly decreased at lower
concentration. First, the absence of a splitting or broadening of
the first oxidation process at low concentration informed us that
the two TTF units are equivalent, thus excluding intramolecular
interactions. Secondly, the concentration dependence and the
splitting at higher concentrations provided evidence for the
existence of intermolecular interactions and the formation of
mixed-valence and radical cation dimer states. These results
clearly demonstrated the presence of an intermolecular mixed-
valence phenomenon.
According to these first results, the following model could be
proposed in agreement with the successive oxidation steps in
the CV of molecular clips 1, 2 and 3 (Scheme 3). Because the
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Figure 3: Cyclic voltammograms of molecular clips 1, 2, 3, 4 and F4-TCNQ at 10−3 M in 0.1 M TBAPF6/CH2Cl2/CH3CN 3:1 on a glassy carbon elec-
trode at 100 mV·s−1.
two TTF units are equivalent, the first oxidation step of the clip shown on CVs suggested that this clip with two radical cations
involves a one-electron process on each TTF unit, leading to the stack with and/or without self-assembly affording mixed-
clip bearing two radical cations. The concentration dependence valence or π-dimer interactions. At higher potential, the tetra-
Figure 4: Cyclic voltammograms of molecular clip 2 at different concentrations (left: 10−5 M; middle: 10−4 M; right: 10−3 M) in 0.1 M TBAPF6/CH2Cl2/
CH3CN 3:1 on a glassy carbon electrode at 100 mV·s−1. Red dashed line: electrochemical simulation performed from experiments (E1 = 0.090 V,
E2 = 0.165 V, E3 = 0.435 mV, KMV = 11400 M−1, KDIM = 680 M−1, kf = 1 × 109 M−1·s−1 for all the forward reactions, α = 0.5 and ks = 0.01 cm·s−1 for all
the charge transfers).
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Beilstein J. Org. Chem. 2015, 11, 1023–1036.
Scheme 3: Graphical representation of the stepwise oxidation of molecular clips 1, 2 and 3.
cation is provided by another one-electron process on each TTF scheme). Due to the equivalence of the two TTF units, it is
unit leading to a clip bearing two dications.
important to note that the input value of the concentration of D
in Scheme 4 (D represents one TTF unit of the clip) must be
The graphical representation can be simulated by an electro- twice that of the experimental concentration of a molecular clip.
chemical simulation program (DigiElch 7) involving an electro- The good agreement between experimental data and modelled
chemical mechanism (Scheme 4) composed by three one-elec- CVs over the whole range of concentration supports the graphi-
tron processes and two charge-coupled chemical reactions (i.e., cal representation of the stepwise oxidation of molecular clips
formation of mixed-valence and dimerization via a square 1, 2 and 3 (Scheme 3).
Scheme 4: Electrochemical mechanism used to simulate the CVs of molecular clips 1, 2 and 3.
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Beilstein J. Org. Chem. 2015, 11, 1023–1036.
Optical and spectroelectrochemical
properties
5 × 10−5 M, only two absorption bands (i.e., 450 and 600 nm)
were observed (Figure 6). Confirming a concentration depend-
The optical properties of oxidized states of molecular clip 1 ence, the absorbance profile at 5 × 10−4 M was different from
were monitored by UV–vis–NIR spectroscopy, by successive the one obtained at 5 × 10−5 M. Two additional absorption
aliquot addition of NOSbF6 (5 × 10−3 M in CH3CN) used as bands simultaneously emerged at the beginning of the oxi-
oxidizing reagent in a solution of clip 1 (10−4 M in CH2Cl2) in a dation process and the end of the reduction process: one at
quartz cell (0.2 cm) (Figure 5). Clip 1 bearing methoxycar- 825 nm and a broad band in near infrared range beyond
bonyl groups at the periphery of the TTF framework was 1300 nm (Figure 6).
chosen because, to our knowledge, the optical characteristics of
such a TTF derivative have not been yet reported. The redox In agreement with the simulated concentration–time profiles in
potential (+ 0.87 V vs Fc+/Fc) of the NOSbF6 reagent is in thin layer conditions (Figure 6 – bottom), the appearance of the
agreement to allow the oxidation of TTF units. Chemical oxi- absorption bands centered around 825 and beyond 1300 nm
dation led to the rapid disappearance of the band at 320 nm were attributed to the formation of [(TTF)2]+ mixed-valence
attributed to the neutral TTF derivative and to the concomitant dimer [47,48] and the absorption bands centered around 600 nm
development of new bands characteristic for the cation radical to the (TTF˙+)2 π-dimer [49]. The band close to 825 nm could
and/or the π-dimer (440, 595 nm), bands which are character- be assigned to cation radicals stack with self-assembly affording
istic for substituted TTF derivatives. After addition of nearly mixed-valence. Nevertheless, at this stage, it would be prema-
two equivalents of oxidizing reagent, we noted the appearance ture to conclude with certainty. The origin of this band is
of the absorption band characteristic of the formation of the currently under investigation and requires complementary
TTF dication (340 nm). As soon as we started to add aliquots of studies to carry out on different substituted molecular clips.
NOSbF6 oxidant onto molecular clip 1, we could observe in the
NIR region an absorption band centered at approximately By analogy with unsubstituted TTF derivative, these three
815 nm and a broad and weak band between 1300–2000 nm. bands reasonably support the presence of mixed-valence and
cation radical dimers during the oxidation process. Whereas the
phenomenon of dimer formation of the TTF cation radical is
commonly observed in the solid state, it was also described in
solution at low temperature in a concentrated TTF solution [50],
or at room temperature in a dilute solution. In the latter case, the
characterization of [(TTF)2]+˙ mixed-valence dimer and/or
(TTF+˙)2 dimer species concerned systems for which the dimer
stabilization is resulting from the close proximity of the two
TTF units. That is the case for conjugated bisTTF systems [51],
bisTTF-substituted calix[4]arenes [52], or supramolecular archi-
tectures such as [3]catenane [53], cucubit[8]uril [54] or self-
assembled cages [55] which facilitate the formation of TTF
dimers.
Studying the glycoluril-based molecular clip 15 presenting also
TTF sidewalls [56,57], Chiu et al. have observed the mixed-
valence and radical cation dimer states at high concentration
(10−3 M) and at room temperature [58]. Indeed, the CV of mo-
lecular clip 15 exhibited four consecutive oxidation waves,
Figure 5: Chemical oxidation of molecular clip 1 (10−4 M, CH2Cl2)
using aliquots of NOSbF6 oxidizing reagent (5 × 10−3 M, CH3CN).
which were interpreted by a succession of oxidation processes
of the TTF sidewalls (Figure 7). These dimer interactions were
predicted to exist at room temperature by theoretical investi-
Known to be a powerful tool for analyzing the formation of gation realized on this system [59].
π-dimers (DIM) and mixed-valence (MV) systems, time
resolved spectroelectrochemical experiments [44-46] were By comparison with these results observed for molecular clip
performed on molecular clip 1 in order to probe the first oxi- 15 [58], it is clear that clips 1–3 exhibit [(TTF)2]+˙ mixed-
dation step at two different concentrations between 350 valence dimer and/or (TTF+˙)2 dimer species but their self-
and 1700 nm in 0.1 M TBAPF6/CH2Cl2/CH3CN (3:1). At association organization could not be yet demonstrated. The
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Beilstein J. Org. Chem. 2015, 11, 1023–1036.
Figure 6: Spectroelectrochemical experiment of molecular clip 1 during the first oxidation step at different concentrations (left: 5 × 10−5 M; right :
5 × 10−4 M) in 0.1 M TBAPF6/CH2Cl2/CH3CN (3:1) on glassy carbon on Pt electrode in thin layer conditions (close to 50 µm) electrode at 5 mV·s−1
and 293 K. (top) CV in current vs time representation. (middle) 3D representation: x-axis = wavelength, y-axis = time and z-axis = absorbance.
(bottom) concentration-time profiles of each simulated species in the thin layer (50 µm) calculated from electrochemical simulations of Figure 4
(E1 = 0.090 V, E2 = 0.165 V, E3 = 0.435 mV, KMV = 11400 M−1, KDIM = 680 M−1, kf = 1 × 109 M−1·s−1 for all the forward reactions, α = 0.5 and
ks = 0.01 cm·s−1 for all the charge transfers).
presence of more or less sterically bulky groups at the periphery appeared in a head-to-tail arrangement and short TTF···TTF
of the TTF moieties does not provide an advantage for the self- intermolecular distances (3.51 Å) were determined between two
assembly of dimers. Moreover, this dimerization phenomenon clips in the solid state.
which is driven by the inclusion of one sidewall into the cavity
of the opposing clip is not observed in the solid state for clips 2 Binding properties
and 3 (Figure 8). This typical packing arrangement was previ- In order to establish the influence of electronic and spatial prop-
ously observed in many cases of glycoluril-based molecular erties of the clips towards binding ability of neutral electrodefi-
clips containing two aromatic sidewalls [26,60-63]. On the cient guest molecules, we have chosen compounds 3 and 4 for
contrary, considering the unit cell for single crystals of clip 2, this study. Molecular clip 3 presents better π-donating ability
X-ray analysis showed that two neighboring molecules of clip 2 according to CV study and a smaller interplanar TTF distance
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Figure 7: Molecular structure of molecular clip 15 and representation of its stepwise oxidation processes proposed by Chiu et al. [58].
(7.41 Å compared to calculated 9.2 Å for clip 4). Binding prop- plexation of m-DNB using a glycoluril-based receptor bearing
erties were studied using 1,3-dinitrobenzene (m-DNB) as a 2,7-dimethoxynaphthalene walls (Ka = (115 ± 10) M−1 ) [64]. In
weak and small aromatic electron acceptor molecule. It should the latter case, it was proposed that binding was occurring
be noted that Nolte et al. have successfully observed the com- through an induced-fit mechanism with a recognition process on
Figure 8: Molecular packing diagram of clips 2 (left) and 3 (right) obtained from X-ray analysis. A molecule of CH2Cl2 is included inside the cavity of
each clip. Hydrogen atoms are omitted for clarity.
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Beilstein J. Org. Chem. 2015, 11, 1023–1036.
the basis of the size rather than the acceptor strength. We can F4-TCNQ (10−5 M in CH2Cl2). Addition of aliquots of molecu-
suppose that the presence of stronger π-donor TTF sidewalls in lar clip 3 onto a F4-TCNQ solution showed the presence of an
clip 3 favorize donor–acceptor interactions and consequently isosbestic point at 395 nm with the concomittent formation and
the binding properties towards m-DNB. We have also checked increase of bands at 760 and 860 nm which could be attributed
the influence of the redox properties towards binding ability by to the progressive formation of the F4-TCNQ radical anion
studying the strong electrodeficient acceptor F4-TCNQ.
(Figure 10) [67,68]. The increase of the bands around 750 and
850 nm was attributed to the cumulative contribution of the
increasing formation of TTF cation radical species and the
Interaction with 1,3-dinitrobenzene (m-DNB)
The host–guest affinity was detected by UV–visible spec- F4-TCNQ anion radical.
troscopy upon titration of clip 3 (10−3 M in o-C6H4Cl2) with
addition of m-DNB (10−1 M in o-C6H4Cl2) aliquots. No addi-
tional change of the spectra was observed after the addition of
one equivalent of m-DNB (−1.30 V vs Fc+/Fc) [65] which is in
agreement with the formation of a 1:1 complex. A Job plot
carried out in o-C6H4Cl2 between clip 3 and m-DNB shows a
maximum at 0.5, confirming the formation of the 1:1 complex
(m-DNB@clip 3) (Figure 9 left). The association constant was
determined to be Ka = (7 ± 3) × 103 M−1 by exploiting the Job
plot analysis according to literature [66]. Despite many efforts
devoted to the search for a complexation of m-DNB using mo-
lecular clip 4, we could not observe any host–guest binding
interaction. These results suggest that electronic and spatial
properties of the cavity constitute fundamental parameters for
binding the m-DNB guest. The binding of such a weak electron
acceptor was successful for molecular clip 3 presenting the
most suitable intramolecular distance between TTF sidewalls
and the strongest π-donor ability.
Interaction with tetrafluoroquinodimethane
(F4-TCNQ)
The binding affinity of molecular clip 3 (5 × 10−4 M in CH2Cl2)
Figure 10: UV–visible absorption spectra of F4-TCNQ (CH2Cl2,
10−5 M) upon titration with molecular clip 3 (CH2Cl2, 5 × 10−4 M).
was studied by a UV–visible titration with the electron acceptor
Figure 9: Left: Job plot analysis for DNB vs molecular clip 3 ([3 + DNB] = 10−3 M in o-C6H4Cl2 at 800 nm) at room temperature. Middle: Job plot for
F4-TCNQ vs molecular clip 3 at room temperature ([3 + F4-TCNQ] = 10−5 M in CH2Cl2 at 860 nm) consistent with a 2:1 binding stoichiometry. Right:
Job plot for F4-TCNQ vs molecular clip 4 at room temperature ([4 + F4-TCNQ] = 10−5 M in CH2Cl2 at 860 nm) in agreement with a 1:1 binding
stoichiometry.
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Beilstein J. Org. Chem. 2015, 11, 1023–1036.
A Job plot carried out in CH2Cl2 between clip 3 and F4-TCNQ correspond to the binding of F4-TCNQ inside the cavity of clip
exhibited a maximum at around 0.7, a finding that corroborates 4 (Figure 11). This binding of F4-TCNQ also results from
with the formation of a 1:2 complex (F4-TCNQ)2@clip favourable spatial parameters with the increase of the intramole-
3 (Figure 9 middle) with an average binding constant of cular distance between the two TTF sidewalls. Thanks to the
Ka = (8 ± 5) × 108 M−1.
good π-donor ability of the TTF sidewalls, in combination with
a well-suited size of the cavity, it is here demonstrated that mo-
Similar studies were carried out using molecular clip 4 and lecular clip 4 constitutes one of the rare examples of systems
quantitative measurements were performed using UV–visible exhibiting good affinity for sandwiching F4-TCNQ as an elec-
titration considering the changes in the spectra of F4-TCNQ at tron poor guest.
860 nm upon addition of sensor 4. The construction of the Job
plot is in agreement with the 1:1 binding stoichiometry between Conclusion
clip 4 and F4-TCNQ with a maximum centered at a molar ratio We have presented original synthetic strategies leading to
of 0.5 (Figure 9 right). The high association constant glycoluril-based molecular clips containing electroactive TTF
Ka = (1.3 ± 0.8) × 106 M−1 in CH2Cl2 confirms that this rigidi- sidewalls. In particular, the one-step preparation of molecular
fied molecular clip 4 is an efficient receptor for F4-TCNQ guest clip using the N-tetraalkylation of glycoluril constitutes a
electron acceptor.
powerful versatile method allowing an easy access to new
architectures for which electrochemical properties can be tuned
This difference in binding interaction between host molecular by simple modification of peripheral substituents on the TTF
clips 3 and 4 towards the F4-TCNQ guest could be explained by moiety. Cyclic voltammetry and spectroelectrochemical
their electrochemical properties. By comparing the first oxi- measurements demonstrated that the mixed-valence state in
dation potential of clips 3 and 4 with the first reduction poten- these fused glycoluril-TTF molecular clips seems to originate
tial of F4-TCNQ (Eapp0red1 = + 0.14 V vs Fc+/Fc – Figure 3), it from intermolecular TTF interactions, according to measure-
is clear that F4-TCNQ guest presents a high reduction potential, ments at various concentrations and to cyclic voltammogram
sufficient to allow the oxidation of molecular clip 3. Conse- simulations. Spatial and electrochemical properties were shown
quently, the (F4-TCNQ)2@clip 3 complex should result from a to be fundamental parameters towards the binding interaction of
redox interaction between the host and the guest. On the other a weak (m-DNB) or strong (F4-TCNQ) electrodeficient guest.
hand, the oxidation potential of molecular clip 4 is increased Consequently, the selectivity for a given target guest could be
due to the introduction of the naphthoquinone spacer. Conse- precisely tuned via the choice of the molecular clip according to
quently, the corresponding 1:1 stoichiometry should reasonably its electrochemical and spatial considerations.
Figure 11: Redox interaction (left) and complexation (right) of F4-TCNQ with molecular clips 3 and 4.
1034

Beilstein J. Org. Chem. 2015, 11, 1023–1036.
Experimental
Synthesis
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Molecular clips 1–3 [18] and 4 [19] were synthesized according
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Electrochemical and spectroelectrochemical
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Electrochemistry and time-resolved spectroelectrochemistry in
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out using a platinum wire counter electrode and a silver wire as
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Acknowledgements
This work was supported by the Ministère de la Recherche et de
l’Enseignement Supérieur for Ph.D grants to Y. Cotelle and M.
Hardouin-Lerouge.
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