Selective access to constitutionally identical, orientationally isomeric calix[6]arene-based [3]rotaxanes by an active template approach

Article abstract of DOI:10.1039/d1sc00279a

Tris(phenylureido)calix[6]arene is endowed with unique properties that make it a valuable macrocyclic component for the synthesis of mechanically interlocked molecules. Its three-dimensional and intrinsically nonsymmetric structure is kinetically selective toward two processes: (i) in apolar media, the threading of bipyridinium based axle-like components takes place exclusively from the upper rim; (ii) SN2 alkylation reactions of a pyridylpyridinium precursor engulfed in the cavity occur selectively at pyridylpyridinium nitrogen atom located at the macrocycle upper rim (active template synthesis). Here we exploit such properties to prepare two series of [3]rotaxanes, each consisting of three sequence isomers that arise from the threading of two identical but nonsymmetric wheels on a symmetric thread differing only for the reciprocal orientation of the macrocycles. The features of the calix[6]arene and the active template synthetic approach, together with a careful selection of the precursors, enabled us to selectively synthesise the [3]rotaxane sequence isomers of each series with fast kinetics and high yields.

Full text of DOI:10.1039/d1sc00279a

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Selective access to constitutionally identical,
orientationally isomeric calix[6]arene-based [3]
Cite this: Chem. Sci., 2021, 12, 6419
rotaxanes by an active template approach†
All publication charges for this article
have been paid for by the Royal Society
of Chemistry
Margherita Bazzoni, a Leonardo Andreoni, b Serena Silvi,
b Alberto Credi,
cd
*
a
a
a
*
*
Gianpiero Cera,
Andrea Secchi
and Arturo Arduini
Tris(phenylureido)calix[6]arene is endowed with unique properties that make it a valuable macrocyclic
component for the synthesis of mechanically interlocked molecules. Its three-dimensional and
intrinsically nonsymmetric structure is kinetically selective toward two processes: (i) in apolar media, the
threading of bipyridinium based axle-like components takes place exclusively from the upper rim; (ii) SN2
alkylation reactions of
a pyridylpyridinium precursor engulfed in the cavity occur selectively at
pyridylpyridinium nitrogen atom located at the macrocycle upper rim (active template synthesis). Here
we exploit such properties to prepare two series of [3]rotaxanes, each consisting of three sequence
isomers that arise from the threading of two identical but nonsymmetric wheels on a symmetric thread
differing only for the reciprocal orientation of the macrocycles. The features of the calix[6]arene and the
active template synthetic approach, together with a careful selection of the precursors, enabled us to
selectively synthesise the [3]rotaxane sequence isomers of each series with fast kinetics and high yields.
Received 14th January 2021
Accepted 31st March 2021
DOI: 10.1039/d1sc00279a
rsc.li/chemical-science
In more recent times, Leigh and co-workers introduced
a new approach, termed as active template approach, in which
Introduction
a metal ion, complexed to the macrocycle, both pivots the
organisation of the axle precursors around the macrocyclic
cavity and mediates the formation of the covalent bonds
between them to create the mechanical link.8 Starting from this
seminal work, a growing number of different metal-catalysed
reactions have been exploited for the realisation of several
otherwise inaccessible MIMs.9–12
A challenging task for the bottom-up construction of molecular-
level working devices, designed to perform programmed func-
tions, is to organise in space the functional groups and binding
sites responsible for their performance with the highest
possible precision and in a predetermined manner.1–4 In this
context, mechanically interlocked molecules (MIMs) such as
rotaxanes are among the most extensively studied platforms.4,5
In typical instances, their synthesis relies on forming a pseu-
dorotaxane precursor between a macrocycle and an axle-type
component, guided by molecular recognition. The insertion of
bulky substituents (stoppers) at the axle's termini eventually
leads to a rotaxane formation. This threading and capping
synthetic strategy, dened as a passive template,6 allows the
synthesis of MIMs with sophisticated molecular architectures.7
It nevertheless appears that the increase of the structural
complexity parallels the difficulties in governing/addressing the
proper relative position and orientation of their active compo-
nents. This issue is particularly relevant when the components are
nonsymmetric13–15 and heteroditopic,16–18 and constitutes a serious
obstacle towards the functional exploitation of such valuable
structural features. In this regard, among the plethora of macro-
cycles so far employed for the construction of molecular devices
based on MIMs, calixarenes represent a recent and unusual
example of a three-dimensional, nonsymmetric and heteroditopic
host.19,20 We have extensively investigated the tris-(N-phenylureido)
calix[6]arene (CX) (Fig. 1) as a macrocyclic component for the
construction of MIMs.21,22 It was evidenced that, in low polarity
media, nonsymmetric N,N0-dialkylbispyridinium (viologen) salts
can thread the calix[6]arene annulus exclusively with their shorter
alkyl chain and through the macrocycle upper rim, thus yielding
oriented pseudorotaxane complexes. Therefore, by adopting the
passive template synthesis, the preparation of rotaxanes charac-
terised by the univocal orientation of the calixarene rims with
respect to the dumbbell was achieved (Fig. 1a).23–27
a
`
Dipartimento di Scienze Chimiche, della Vita e della Sostenibilita Ambientale,
`
Universita di Parma, Parco Area delle Scienze 17/A, I-43124 Parma, Italy. E-mail:
arturo.arduini@unipr.it; andrea.secchi@unipr.it
b
`
Dipartimento di Chimica “G. Ciamician”, Universita di Bologna, Via Selmi 2, I-40126
Bologna, Italy. E-mail: serena.silvi@unibo.it
c
`
Istituto per la Sintesi Organica e la Fotoreattivita, Consiglio Nazionale delle Ricerche,
Via Gobetti 101, I-40129 Bologna, Italy
d
`
Dipartimento di Chimica Industriale “Toso Montanari”, Universita di Bologna, Viale
del Risorgimento 4, I-40136 Bologna, Italy
† Electronic supplementary information (ESI) available: Synthetic procedures,
NMR and HR-MS spectral characterisation, UV/Vis and electrochemical data for
the series of synthesised calix[6]arene-based [3]rotaxanes. See DOI:
10.1039/d1sc00279a
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Fig. 1 Graphical representation of the synthesis of [2]rotaxanes based on a calix[6]arene wheel (CX), for the sake of simplicity represented as
a yellow cartoon, and bipyridinium (viologen) axles using either the passive (a) or the active (b) template synthesis.
More recently, efficient synthetic routes to pseudorotaxanes C12) of the linkers connecting each viologen unit to its diphe-
and rotaxanes through a metal-free active template approach were nylacetyl stopper. Within the two series, three distinct orienta-
devised.28–30 In this context, we have exploited the engulfment of tional isomers characterised by the different reciprocal
positively charged pyridylpyridinium salts inside the p-rich
cavity of CX for the selective synthesis of orientational isomers
of calix[6]arene-based [2]rotaxanes (Fig. 1b).31,32 As a conse-
quence of its inclusion, the bound salt exposing its neutral
nitrogen to the upper rim of the calixarene experiences a faster
reactivity towards an SN2 reaction, leading to the formation of
oriented pseudorotaxanes and rotaxanes with faster kinetics
and higher yields compared to the classic threading and
capping strategy (passive template approach).33–37 This
supramolecular-assisted strategy could thus expand the scope
for the efficient synthesis of calix[6]arene-based MIMs with
strict control on the mutual orientation of their nonsymmetric
molecular components (Fig. 1b).26,32,38
Motivated by the general interest in higher-order rotaxanes
as prospective nanodevices,39–45 and by our expertise in the
synthesis of calix[6]arene-based oriented (pseudo)rotaxanes and
catenanes,46,47 here we report on the preparation and properties
of two series of calix[6]arene-based [3]rotaxanes congurational
isomers (Fig. 2). Their common structural features are two calix
Fig.
2 Schematic representation of the [3]rotaxane orientational
[6]arene wheels threaded by a dumbbell terminating with two
identical stoppers, in which a C12 alkyl chain spans two viol-
ogen units. The two series are distinguished by the length (C6 or
isomers object of this study. The labels UU, UL and LL stand for upper–
upper, upper–lower and lower–lower, and denote which rims of the
two calixarene wheels are proximal in the rotaxane. The tosylate
counteranions have been omitted for clarity.
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orientation of the two calix[6]arenes that surround the two
viologen units of the dumbbell were devised. Orientational
isomers indicated as UU and LL present the two calix[6]arene
wheels facing each other through their upper or lower rims,
respectively. In the UL isomers, the two wheels are instead
oriented head-to-tail along with the dumbbell (Fig. 2). Due to
their structural complexity, these molecular systems will be
hereaer described with apposite labels like R6UU, in which R
denotes a rotaxane compound, while the number indicates the
length of the alkyl chain linkers between the viologen units and
the stoppers, and the subscripts point out the reciprocal
orientation of the two wheels as described above (Fig. 2). The
synthesis and the complete structural characterisation of the
novel six [3]rotaxanes will be discussed, along with their elec-
trochemical properties.
It should be emphasised that our compounds address the
problem of sequence isomerism in [3]rotaxanes48–50 by taking
advantage of the inherent orientation of the calixarene wheel
along the main axis of the rotaxane.51 Neri and co-workers
recently reported the elegant synthesis of calixarene-based [3]
rotaxanes with UU and LL arrangements by a passive template
synthesis.52,53 In these systems, a “through annulus” ring
inversion of the two wheels, enabled by acid–base stimuli,
allowed the observation of all three orientational isomers. In
such compounds, however, the three isomers were not isolated.
The present study aims at demonstrating that our active
template synthesis affords (i) full control of the geometrical
arrangement of the calix[6]arene wheels encircling the axle, and
(ii) the preparation with high yields of sophisticated interlocked
structures, otherwise inaccessible by classic threading and
capping strategies (passive template synthesis).
Scheme 1 Reagents and conditions: (i) Ph2CHCOCl, Et3N, DCM, rt,
8 h; (ii) 4,40-bipy (2 eq.), CH3CN, reflux, 24 h; (iii) 4,40-bipy (2.5 eq.),
CH3CN, reflux, 24 h; (iv) 1,12-dibromododecane (5 eq.), CH3CN, reflux,
7 d; (v) 4a,b, CH3CN, sealed tube, 100 ꢀC, 7 d. In the cartoons of the [3]
rotaxane structures, the counteranions have been omitted for clarity.
Results and discussion
approach were of the UU-type, R6UU and R12UU, which differ
for the length of the outer dumbbell arms. In reactions {A} of
Scheme 1, CX was equilibrated in toluene with the appropriate
dumbbell components DC-2 (4a for R6 and 4b for R12) and DC-3
using a CX : DC-2 : DC-3 ¼ 2.5 : 2.4 : 1 stoichiometric ratio. The
resulting mixture was heated at 65 ꢀC for at least seven days. In
these two runs, [3]rotaxanes R6UU and R12UU were obtained in
62% and 43% yield, respectively, aer chromatographic sepa-
ration. No other orientational isomers were separated from the
reaction mixtures. The preparation of the LL-type isomers R6LL
and R12LL was carried out similarly, but using the dumbbell
components DC-1 (3a for R6 and 3b for R12) and DC-4 as
starting reagents (see reactions {C} in Scheme 1). These two [3]
rotaxanes were isolated in 50% (R6LL) and 38% (R12LL) yields.
Once again, no other orientational isomers were separated from
the respective reaction mixtures.
As mentioned in the Introduction (Fig. 1b), we have recently
developed a very efficient one-pot synthetic method that allows
us to synthesise several types of oriented [2]rotaxane regardless
of the length of the arms of the resulting viologen-based
dumbbell.31,32 The dumbbell is formed inside the calix[6]arene
reactor by joining two sub-components: a stoppered pyr-
idylpyridinium precursor and a stoppered alkylating agent. It is
important to point out that the sole [2]rotaxane isolated in this
one-pot reaction will always have the stopper of the pyr-
idylpyridinium precursor at the calix[6]arene lower rim (red
stopper in Fig. 1b). The necessary synthetic precursors for the
synthesis of the [3]rotaxanes depicted in Fig. 2 – hereaer
indicated as dumbbell components (DC1–5) – were appropri-
ately chosen like pieces of a molecular Meccano by considering
that in low polarity solvents: (i) mono-stoppered viologen-based
axles always thread the cavity of CX from its upper rim, and (ii)
the alkyl chain initially present on the pyridylpyridinium
precursors will be in proximity of the lower rim of the wheels in
the resulting [3]rotaxane.
For the synthesis of the third series of [3]rotaxane orienta-
tional isomers, R6UL and R12UL, in which both the nonsym-
metric calix[6]arene wheels are oriented in the same direction
with respect to the thread, a slightly different synthetic
sequence was adopted (see reactions {B} in Scheme 1). DC-5 (6a
for R6 and 6b for R12) was initially suspended in toluene at
The synthesis of DC1–5 was summarised in Scheme 1 (see
ESI† for the experimental details). The free dumbbells 7a,b were
also synthesised for comparison. The rst [3]rotaxane orienta-
tional isomers prepared with the supramolecular-assisted
ꢀ
80 C with a twofold stoichiometric excess of CX to give a [2]
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pseudorotaxane orientational isomer in which the stoppered (Fig. S25–S30†) show molecular peaks (triply and quadruply
arm of the viologen-based axle is located at the wheel upper charged) with an isotopic distribution in agreement with the
rim.‡ The formation of such complex was witnessed by the deep structure of the two [3]rotaxanes series. The 1H NMR spectra in
red colour assumed by the now homogeneous solution aer CDCl3 of the [3]rotaxanes sharing the same dumbbell 7a and
a few hours of stirring. The resulting pseudorotaxane complex isolated from the reactions {A–C} are shown in the stack plot of
was not isolated but immediately reacted with DC-2 (4a for R6 Fig. 4. As expected, the spectra of the three [3]rotaxanes are not
and 4b for R12) for seven days at 80 ꢀC. In this way, the superimposable. However, the two spectra of R6UU (Fig. 4a) and
supramolecular-assisted reaction occurs between the R6LL (Fig. 4c) have a similar pattern, both showing two well-
protruding u-bromo termini of DC-5, already conned in CX, resolved doublets, with geminal coupling, for the “axial” (4.4
and a new complex resulting from the association of DC-2 and ppm) and “equatorial” (3.5 ppm) diastereotopic protons of the
the excess of CX already present in the solution. Aer workup calix[6]arene wheels bridging methylene groups (see black
and chromatographic separation, the desired [3]rotaxanes R6UL circles in Fig. 4a and c). On the contrary, the spectrum of R6UL
,
and R12UL were obtained in 42% and 40% yield, respectively. isolated from reaction {B}, shows at ꢁ3.5 ppm (see white circles
Analysis of the crude reaction mixture did not allow us to in Fig. 4b) two overlapped doublets suggesting the head-to-tail
identify unambiguously if any other stereoisomers were formed arrangement of the calixarene macrocycles with respect to the
in the reaction. However, aer careful chromatography, only the dumbbell.
target geometric isomer was observed in fractions identied as
To assess the structure of these MIMs, extensive NMR
containing [3]rotaxane by LC-MS. As the same eluent system experiments were carried out to identify the isolated spin
was used to isolate R6UU and R6LL, this provides strong evidence systems of the inner chain and external arms and their position
for the stereoselectivity of the reaction.
with respect to the rims of the calix[6]arene macrocycles. The
The identity of the isolated compounds was initially inves- proton signals arising from the internal (a to z) and external (1
tigated through HR-MS measurements. The recorded spectra to 6) alkyl chains of the dumbbell in R6UU were unequivocally
Fig. 3 1H NMR stack plot (400 MHz, CDCl3) of (a) wheel CX, (b) [3]rotaxane R6UU, and (c) dumbbell 7a. For solubility reasons, spectrum (c) was
taken in CD3OD. The most representative resonances are labelled according to the molecular sketches placed above the stack plot, while their
complexation induced shifts are indicated with solid lines; the unlabeled signals marked with an asterisk in the spectrum (b) belong to a rotamer
of R6UU in the partial cone (paCo) conformation; see text and ESI† for further details.
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assigned through a series of 1D and 2D NMR experiments. orientation of the wheels. Very similar behaviour was observed
Initially, the 1H NMR spectra of R6UU, the empty wheel CX, and for the two pairs of protons (U,#) and ($,§) of the viologen units.
the free dumbbell 7a were gathered in the stack plot of Fig. 3 Because of the symmetry, in the spectrum of the free 7a (Fig. 3c),
(for the protons labelling, see the molecular sketches in Fig. 3 the signals of these protons' pairs are overlapped. However, in
and 4). From previous studies carried out on calix[6]arene-based R6UU, these viologen units experience an anisotropic magnetic
[2]rotaxanes,54–56 it is known that the methine proton (labelled environment exerted by the nonsymmetric calixarene cavities.
as 0) of the diphenylacetic stoppers yields a diagnostic singlet at Thus, their signals are split into four upeld-shied resonances
ca. 5 ppm. In R6UU, this signal is found at 5.07 ppm (see Fig. 3b at 7.67 (U), 7.32 (§), 6.67 (#) and 6.17 ($) ppm (see purple lines in
and 4a). In the rotaxanes, several signals of the dumbbell are Fig. 3b and c).
upeld-shied (cf. Fig. 3b and c) because of its inclusion inside
Moving forward along the dumbbell's internal and external
the cavities of CX. Through a 2D HSQC experiment (Fig. S3†), we alkyl chains, up to the methylene groups (d) and (2), different
were able to identify the resonance of the methylene groups (1) but very diagnostic shielding effect of the calixarene cavities
adjacent to the diphenyl acetic stopper. Starting from this signal could be detected. The shielding effect is still very signicant for
and thanks to a 2D TOCSY experiment (Fig. S5†), the whole spin the methylene protons of the internal C12 alkyl chain (Dd ¼
system of the external C6 alkyl chain in R6UU was recognised. +1.4, +0.6, and +0.4 ppm for b, g and d, respectively, see the red-
The same approach allows us to identify the signals from b to shaded box in Fig. 3). In comparison, it is negligible for the
d of the internal alkyl chain starting from the well-recognisable methylene protons (5) [Dd ¼ +0.05 ppm] of the C6 external
a resonance at 3.2 ppm. In this respect, it is worth noticing the chains. A small deshielding effect was instead observed for the
complexation induced shi (CIS) experienced by the signals of methylene (4) to (2) of the same chain (see the blue-shaded box
the two pairs of methylene protons (a) and (6), which are the in Fig. 3). Such an effect can be accounted for by considering
linking units between the encapsulated viologen units and the that, in the postulated structure of R6UU, the methylene group
dumbbell internal and external alkyl chains, respectively. In the (5), with the rest of the chain, protrudes from the macrocycles
free dumbbell 7a, they resonate as two close triplets at 4.72 and lower rim. Thus, the dumbbell external alkyl chains suffer the
4.67 ppm (Fig. 3c), while in R6UU, because of their encapsula- deshielding effect of ethylethyloxy alkyl chains present on the
tion in the wheels, they give rise to two upeld-shied reso- calix[6]arenes lower rim.§ To conrm these ndings, we also
nances at 3.2 (Dd ¼ +1.4) and 3.7 (Dd ¼ +1) ppm, respectively carried out a 2D ROESY experiment that, through the analysis of
(Fig. 3b). Since such complexation only leads to a single set of the resulting cross-peaks, revealed the spatial proximity
shied signals for the methylene protons (a) and (6), it is very between the protons of the inner alkyl spacer (a to d) and the
reasonable to assume that both viologen units experience the aromatic protons (b and c) of the phenylureas at the macro-
same magnetic environment due to the head-to-head cycles upper rim (Fig. 5). Analogous results were obtained for
Fig. 4 1H NMR stack plot (400 MHz, CDCl3) of the [3]rotaxanes sharing dumbbell 7a, isolated from the supramolecular-assisted reactions {A–C}
of Scheme 1, and corresponding to (a) R6UU, (b) R6UL and (c) R6LL, respectively. The U and L subscript labels of the spectrum (b) indicate that the
corresponding protons' chemical shifts coincide with those found for the UU and LL orientational isomers, respectively. In the sketch of the three
[3]rotaxanes on the left, the tosylate counteranions have been omitted for clarity.
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wheels upper rim. A 2D ROESY experiment (Fig. S13†)
conrmed these ndings since it allowed us to identify several
dipolar couplings witnessing the spatial proximity between the
dumbbell methylene groups (3–5) with the wheels phenylurea
groups. Since in R6LL the wheels adopt a tail-to-tail orientation,
the signals of the C12 inner alkyl spacer (a–z) are downeld-
shied with respect to the same resonance in R6UU
.
The 1H NMR spectra of R6UL and R12UL (see Fig. 4b and
S31b†) orientational isomers evidence no matching with the
corresponding UU (see Fig. 4a and S31a†) and LL-type (see
Fig. 4c and S31c†) [3]rotaxane orientational isomers.k Most
importantly, several of their NMR signals are split into two
separated resonances because of the two wheels' head-to-tail
arrangement. In this regard, the splitting of the signals rela-
tive to the wheels bridging methylene groups was briey dis-
cussed. The spectra of these compounds also show two distinct
resonances for the N+CH2 groups sitting at the upper rim of the
wheels. Thanks to a series of 1D TOCSY experiments (Fig. S20†),
it was possible to assign the signal resonating at 3.25 ppm to the
methylene aU while the one resonating at 3.13 ppm to 6L
(Fig. 4b). Indeed, the external alkyl chain spin system starting
from 6L unequivocally leads to a signal resonating at 4.09 ppm
and relative to the OCH2 group 1L. Similarly, a second C6 alkyl
chain starting from the OCH2 (1U) resonating at 4.36 ppm and
leading to (6U) at 3.85 ppm was identied.
Fig. 5 Expansion of a 2D ROESY spectrum (400 MHz, CDCl3, ROESY
SL ¼ 200 ms) of R6UU. Analysis of the cross-peaks shows the spatial
proximity between the protons of the internal C12 alkyl chain (a–d) and
those of the phenylurea groups (b and c) present at the upper rim of
the calix[6]arene macrocycles (for the full spectrum, see ESI†).
UV-visible spectroscopic and electrochemical measurements
the [3]rotaxane R12UU (Fig. S21†), endowed with longer C12
external arms. This fact conrms that this synthetic strategy
operates regardless of the length of the threads' external arms,
and it is exclusively affected by the nature of the heteroditopic
calix[6]arene wheel.
It is worth noticing that some weak resonances in the spec-
trum of R6UU, highlighted in Fig. 3b with asterisks, are in
chemical exchange with the dumbbell signals (6), (1), (#) and
(U). These exchanging signals were identied through a series
of selective ROESY and NOESY experiments (see Fig. S7†). The
weak and exchanging resonances are due to a rotamer in the
partial cone (paCo) conformation, likely generated by the rota-
tion of one of the wheel aromatic rings bearing the p-tert-butyl
group (see the sketch in Fig. S7†).{
The UV-visible spectroscopic characterisation of the six [3]
rotaxanes was performed in CH2Cl2. All the compounds show
the typical absorption features of calixarene–bipyridinium
based rotaxanes,26,55 i.e., an intense band in the UV region and
a weak broad band in the visible region of the absorption
spectrum around 450 nm (Fig. S32†). As expected, the molar
absorption coefficients of these two bands are roughly doubled
with respect to parent [2]rotaxanes on account of the presence
of twice as many chromophoric units. The spectral shapes are
very similar and almost superimposable, regardless of the
length of the alkyl chains and the orientation of the calixarene
rings (Fig. S32†).
By a closer inspection of the UV band maximum, however,
a slight shi can be observed for the R6 series (Fig. S33†). The
band is red-shied moving from the UU to the UL and LL
isomers. This behaviour would suggest an effect of the relative
orientation of the calixarene wheels, which can be detected only
for the series with the shorter axle. Indeed, the band is at higher
energy when the three urea moieties face each other and at
lower energy when they point toward the stopper units. As the
wavelength shi is comparable with the resolution of our
instrument, we prefer not to speculate on this observation.
However, it cannot be excluded that in the shorter rotaxanes,
the bipyridinium encapsulation is slightly dependent on the
wheel orientation because of the presence of a nearby stopper.
For comparison, the absorption spectra of the model dumbbells
7a,b were collected (Fig. S34†): unfortunately, these two
compounds are mostly insoluble in CH2Cl2, and their absorp-
tion coefficient could not be measured. Nevertheless,
As we did for the UU-type series of [3]rotaxanes, 2D HSQC
and TOCSY (see ESI†) experiments were carried out on the
samples of the LL-type series (R6LL and R12LL) to identify the
whole spin system of the external C6 alkyl chain in these [3]
rotaxanes. It is important to note that in these [3]rotaxane
isomers, the signals of the external alkyl chains are signicantly
more upeld-shied than for R6UU and R12UU. As an example,
protons of methylene (6) in R6 resonate at ꢁ3.8 ppm for the UU
isomer, while the same protons resonate at ꢁ3.2 ppm in the
spectrum of LL (Dd ꢁ 0.6 ppm) (cf. Fig. 4a and c). Such higher
shielding effect is even more evident for the protons labelled as
(2–5) that in the spectrum of the UU isomer are found between
2.2 and 1.5 ppm (Fig. 4a), while in the LL isomer are at very high
elds (1 to 0.5 ppm, Fig. 4c). These ndings agree with the
hypothesised structure of R6LL in which the external C6 arms
endure the shielding effect of the phenylureas present on the
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a comparison of the shape of the spectra conrms that the (from 0.1 to 1 V sꢂ1). Overall, the [3]rotaxanes show the same
length of the chains has no effect on the optical properties of electrochemical features as the parent [2]rotaxanes. Apparently,
these compounds.
no effect of the chain length and the relative orientation of the
The electrochemical characterisation of the rotaxanes and wheels could be detected. Small effects, like those observed in
the dumbbell model compounds was performed by cyclic vol- the absorption spectra, could be expected, but unfortunately,
tammetry (CV) and differential pulse voltammetry (DPV) in the poor reversibility of the processes prevented a more detailed
CH2Cl2; the data are gathered in Table S2.† Compounds 7a and analysis.
7b show two reduction processes, respectively assigned to the
rst and second monoelectronic reduction of the two bipyr-
idinium units, thus suggesting that they are independent and
Conclusions
non-interacting. Both processes are slightly shied to more We have described a methodology to prepare [3]rotaxanes
negative potential values (ca. 50 mV) with respect to parent comprising two identical heteroditopic nonsymmetric calix[6]
bipyridinium-based axle compounds.57 This observation could arene macrocycles with full control of their mutual orientation.
be related to the scarce solubility of the compounds and the The method, based on an active template effect exerted by the
formation of small aggregates: indeed, the quality of the CV calixarene cavity on the axle subcomponents, ensures large
curves is poor, showing the presence of spurious peaks, possibly exibility to the axle structure. Sets of three isomeric [3]rotax-
related to partial precipitation of the compounds during the anes that are constitutionally identical but structurally non-
measurements.
equivalent, owing to the different relative orientations of the
The electrochemical behaviour of the six [3]rotaxanes is very calixarene wheels, have been prepared and characterised for the
similar (Fig. 6): all the compounds show two reduction rst time. Two series of [3]rotaxanes that differ for the length of
processes, at more negative potential values with respect to the axle components have been synthesised, demonstrating the
model bipyridinium dumbbells and in analogy to parent [2] versatility of the approach. Its success stems from the fact that
rotaxanes.26,55 The presence of only two processes, like in the the programmed isomer is obtained selectively and efficiently,
dumbbell model compounds, suggests that the two bipyr- thus avoiding the need for isolation procedures that, according
idinium units are equivalent and non-interacting with each to our observations, would be particularly problematic. To the
other. The shi of the rst process is ascribed to the charge best of our knowledge, this is the only example in which the
transfer interaction between the bipyridinium units and the three sequence isomers of [3]rotaxanes made of identical axle
calixarene macrocycles, which stabilises the dicationic bipyr- and wheel components originating from the intrinsic asym-
idinium moieties. The shi of the second reduction process metry of the wheel were selectively synthesised and isolated.
suggests that the calixarenes and the monoreduced bipyr-
The development of made-to-order synthetic approaches to
idinium sites are still interacting, as observed for related [2] MIMs that contain nonsymmetric components assembled with
rotaxanes.26,55 In cyclic voltammetric experiments, both reduc- a predetermined mutual orientation is key to explore the
tion curves show some degree of electrochemical irreversibility, virtually unlimited possibilities that the mechanical bond can
with peak-to-peak separation >100 mV at the explored scan rates offer to stereochemistry and its applications. The realisation of
directional motion in molecular machines and the use of
sequences of threaded molecular wheels to store information at
the nanoscale are only two examples of this kind. Various
functional elements – e.g., stoppers, spacers and recognition
sites – can be introduced in the dumbbell-shaped component.
In principle, the strategy discussed here could also be extended
to make higher-order rotaxanes with more than two identical
nonsymmetric wheels threaded in any desired sequence of
relative orientations.
Author contributions
M. B. – investigation, data interpretation, writing & review; L. A.
– investigation, data interpretation, & writing; S. S. – data
interpretation, writing, review, supervision & editing; A. C. –
review, supervision & funding acquisition; G. C. – writing &
review; A. S. – data interpretation, original dra, writing, review,
supervision & editing; A. A. – conceptualization, writing, review,
supervision & funding acquisition.
Fig. 6 Cyclic voltammograms of dumbbell 7a (black line; 1 ꢃ 10ꢂ4 M)
and [3]rotaxane R6UU (red line, 2 ꢃ 10ꢂ4 M) in CH2Cl2 at room Conflicts of interest
temperature. A 100-fold excess of TBAPF6 was employed as sup-
porting electrolyte.
There are no conicts to declare.
© 2021 The Author(s). Published by the Royal Society of Chemistry
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Acknowledgements
The authors thank Centro Interdipartimentale di Misure of the
University of Parma for NMR and MS measurements. This work
was supported by the European Union's Horizon 2020 research
and innovation program (ERC AdG “Leaps” 692981 and FET-
OPEN “Magnify” 801378) and the Italian Ministry of Univer-
sity and Research (PRIN 20173L7W8K and FARE R16S9XXKX3).
This work has been carried out within the COMP-HUB Initia-
tive, funded by the “Departments of Excellence” program of the
Italian Ministry for Education, University and Research (MIUR,
2018–2022).
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