Cucurbit[8]uril-mediated pseudo[2,3]rotaxanes

Article abstract of DOI:10.1039/c9cc07144j

Pseudo[2,3]rotaxanes have been successfully fabricated by the complexation of cucurbit[8]uril (CB[8]) macrocycles with extended viologen derivatives. Two design rules enable the incorporation of a third CB[8] onto a recently reported pseudo[2,2]rotaxane.

Full text of DOI:10.1039/c9cc07144j

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Cucurbit[8]uril-mediated pseudo[2,3]rotaxanes†
a
b
b
a
Guanglu Wu,
Istvan Szabo, Edina Rosta and Oren A. Scherman
*
´
´
Cite this: Chem. Commun., 2019,
5, 13227
5
Received 12th September 2019,
Accepted 4th October 2019
DOI: 10.1039/c9cc07144j
rsc.li/chemcomm
Pseudo[2,3]rotaxanes have been successfully fabricated by the three CB[8] macrocycles would be called a pseudo[2,3]rotaxane
complexation of cucurbit[8]uril (CB[8]) macrocycles with extended of CB[8].
viologen derivatives. Two design rules enable the incorporation of a third
CB[8]-mediated ternary complexes are generally dynamic
CB[8] onto a recently reported pseudo[2,2]rotaxane. Incorporation of a structures in aqueous solution and typically display unresolved
third macrocycle confines the dimeric stacking of chromophores signals in the NMR spectrum. A pseudo[2,2]rotaxane, however,
into specific alignment, leading to effective electron-delocalisation is extremely ‘‘static’’ in aqueous solution with well-resolved
along their long molecular axis.
NMR signals, although it seems like a simple connection of two
15,17
ternary motifs.
As a result, formation of pseudo[2,2]rotaxanes
Cucurbit[n]urils (CB[n]s, n = 5, 6, 7, 8, and 10) are a class of offer a straightforward way to bring two molecules close to each
synthetic macrocyclic molecules that can recognise a wide range other and remain in a stacked orientation for a long period of time,
of guest molecules with strong affinities, particularly in aqueous which facilitates the study of short-range, yet non-instantaneous
1,2
solution. Depending on their cavity size, different CB[n] homo- interactions within a discrete dimer. We attribute the static feature
logues bind with guests containing specific moieties. For instance, of these dimers to the presence of a double CB[8] constrained
a phenyl or p-tolyl group has the perfect size and shape to fit a system, which suppresses dissociation of the two long-axis mole-
CB[7] cavity, resulting in a strong and ‘‘static’’ (on the NMR cules. Therefore, we posit that a pseudo[2,3]rotaxane with three
3
timescale) complexation. CB[8], with a larger cavity volume, can CB[8] macrocycles may produce an even more static dimer by the
simultaneously include two guest components, forming a ternary introduction of an additional constraint.
4
,5
complex. This ternary motif has been widely used as a bridging
The most straightforward route to a pseudo[2,3]rotaxane is
to identify a pseudo[2,2]rotaxane with CB[8] and extend the
4,6,7
unit to link together two objects such as charge-transfer pairs,
peptides and proteins,
macroscopic materials and surfaces.
8,9
10
11,12
polymers, particles,
and even length of its long-axis molecules by incorporating an elongated
core. As shown in Fig. 1, a 2,6-anthracenyl moiety is inserted
13,14
Recently, a 2 : 2 motif containing two rigid and elongated into the centre of a diarylviologen (VMe) motif, which has
1
5,16
15
molecules, constrained by two CB[8] macrocycles,
attracted increasing attention on account of its emerging features Preparation of the designed guest molecule, Ant26Me, starts
has previously been reported to form a 2 : 2 complex with CB[8].
1
5,17
17–19
22
such as red-shifted absorption,
enhanced emission,
with Suzuki–Miyaura cross-coupling of two pyridin-4-yl groups
1
7
20
excimer formation, directional self-sorting, and a negative onto the 2,6-anthracenyl core followed by further transformation
pK shift. This motif appears similar to pseudorotaxanes but of the pryidin-4-yl moieties into tolylpyridinium salts through a
contains more than one long-axis molecules; Cao et al. termed Zincke reaction
such structures as pseudo[n,m]rotaxanes, where ‘n’ is the 1-(p-tolyl)pyridin-1-ium moieties would still behave as ‘‘clamping’’
number of long-axis molecules and ‘m’ is the number of modules to capture two CB[8]s in a dimeric manner while mean-
macrocycles in the complex. Therefore, a 2 : 2 complex can be while exhibiting additional spacing to hold a third macrocycle.
2
1
a
17,23
(Scheme S2, ESI†). We wondered if the two
1
9
described as a pseudo[2,2]rotaxane and a 2 : 3 complex containing
2
A mixture of 2 equiv. Ant26Me with 3 equiv. CB[8] in D O
1
results in a well-resolved H-NMR spectrum (Fig. 2c) where each
signal is assigned through variable-temperature NMR as well as
COSY and NOESY 2D NMR (Fig. S2–S4, ESI†). All the peaks
a
Melville Laboratory for Polymer Synthesis, Department of Chemistry, University of
Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. E-mail: oas23@cam.ac.uk
ꢁ
10
2
ꢁ1
b
exhibit a unified diffusion coefficient (D) of 1.81 ꢀ 10
m s
Department of Chemistry, King’s College London, 7 Trinity Street, London,
measured from DOSY experiments (Fig. S5, ESI†), indicating
SE1 1DB, UK
†
Electronic supplementary information (ESI) available. See DOI: 10.1039/c9cc07144j
that there is only one species in solution with a stoichiometric
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ends and an additional CB[8] held in between surrounding the
anthracenyl cores.
One may notice that two pyridinium signals (Hd,e in Fig. 2) are
split into four peaks upon forming the pseudo[2,3]rotaxane with
CB[8] (H
0
0
in Fig. 2); this is not observed upon complexation
d,d ,e,e
1 2
with CB[7] as a G -CB[7] complex (Fig. 2). A sharpening of these
split signals is observed as the temperature is decreased (Fig. S2,
ESI†), which indicates slow interconversion on the NMR timescale
between two degenerate states. This further suggests restricted
Fig. 1 Evolution from a pseudo[2,2]rotaxane to a pseudo[2,3]rotaxane of intra-complex motion caused by triply-constrained dimeric stacks
ꢁ
CB[8] by incorporating an elongated core into a diarylviologen. The Cl
in the pseudo[2,3]rotaxane. The strong constraint applied by the
presence of three macrocycles not only maintains the two long-axis
counterions are omitted for clarity.
molecules as a discrete and static dimer in aqueous solution but
ratio of 2 : 3, i.e. G
cule). Two sets of signals (Hx,y,z, H
range between 4.0 ppm and 6.0 ppm suggesting the presence of
2
-CB[8]
3
(where G represents a guest mole- also confines their stacking in a controlled alignment, which leads
) are observed in the to unique photophysical properties. As shown in Fig. 2d–i, the
-CB[7] complex ensures a discrete monomeric state of Ant26Me
0 0 0
x ,y ,z
G
1
2
two types of CB[8] macrocycles in one complex. One set of CB[8] displaying a bright yellow fluorescence. The aqueous solution of
peaks exhibit a signal intensity (or integration) that is twice as free Ant26Me molecules without any CB macrocycles exhibits a
large as the other (e.g. H vs. H ). This corresponds to two light orange emission, suggesting a certain degree of aggregation
z
0
z
CB[8]s that are bound with tolyl groups from both ends as the in water, which is further confirmed by its concentration-
CB[8] protons only exhibit cross-correlation NOESY signals with dependent NMR spectra (Fig. S6, ESI†). The formation of a
protons from tolyl moieties such as [H , Ha,b,c] (Fig. S4, ESI†). pseudo[2,3]rotaxane of Ant26Me with CB[8] shows a significant
z
Since the two portals of this type of CB[8] are exposed to an bathochromic-shift in both absorption and emission, displaying a
asymmetric chemical environment, their methylene protons bright red emission and a broad spectrum window of 300 nm
1
5
display a characteristic split pattern, i.e. Hx1,x2,y1,y2. On the between the excitation peak at 355 nm and emission peak at
other hand, a different CB[8] environment arises from the 657 nm. This large spectral shift suggests a substantial extent of
macrocycle that must be binding with the anthracenyl cores, electron-delocalisation on account of the dimeric stacking
as its protons (H
0
0
0
) only display cross-correlation NOESY along the long molecular axis, which cannot happen without the
x ,y ,z
signals with Hf,g,h,i rather than Ha,b,c (Fig. S4, ESI†). Moreover, confinement and protection from three CB[8] macrocycles. On
no signal splitting is observed for this CB[8], which is consis- the other hand, the free Ant26Me molecules can also stack into
tent with symmetric CB[8] portals in proximity to the central aggregates, but only in an arbitrary manner without a well-defined
core. Compared to the spectrum of unbound Ant26Me (Fig. 2a), directional alignment of the anthracenyl cores (Fig. 2d).
the upfield shift of tolyl and anthracenyl protons as well as the
Replacing the 2,6-anthracenyl core by a shorter 2,6-naphthyl
downfield shift of pyridinium protons also confirm the formation moiety, Np26Me also results in the formation of a pseudo[2,3]-
of a pseudo[2,3]rotaxane with two CB[8]s complexing the tolyl rotaxane with CB[8] (Fig. S7, ESI†). Moreover, it can form a
1
Fig. 2 H-NMR (a–c), absorption/emission spectra (d–f), and photographs of solutions excited by a 365 nm lamp (g–i) for Ant26Me (G), G
1
-CB[7]
2
, and
G
2 3
-CB[8] , respectively, at 298 K. Emission spectra were obtained by excitation at the maximum absorption wavelength of each species between 330 nm
and 360 nm. Concentrations of G are 500 mM in (a) and 65 mM in (b) and (c) for NMR studies, 10 mM for absorption measurements, and 30 mM for emission
measurements as well as solutions depicted in the photographs. For a clear comparison, the intensity of the signals in the NMR spectra between 1.7 ppm
and 6.0 ppm has been reduced.
1
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pseudo[2,1]rotaxane quantitatively in a mixture of 1 equiv.
On the other hand, increasing the slippage between the two
CB[8] and 2 equiv. Np26Me, displaying absorption and emis- long-axis molecules may be possible through an alternative
sion spectra similar to that of its pseudo[2,3]rotaxane (Fig. S8, route, specifically by adjusting the steric demands at the end
ESI†) on account of the same dimeric stacking. However, the groups to arrive at a pseudo[2,3]rotaxane. Moreover, a larger
mixture of 1 equiv. CB[8] and excess Ant26Me (Z2 equiv.) leads end group may further extend the central spacing by pushing
to a co-existence of several complexes in competition. Further the two outer macrocycles away from the central core. This is
shortening the central core to a 1,4-phenyl moiety, Ph14Me demonstrated by a study of the complexation between CB[7]
does not lead to the formation of a pseudo[2,3]rotaxane with and a series of long-axis molecules (Np14R) containing
1
7
CB[8] as it only forms a pseudo[2,2]rotaxane.
1,4-naphthyl cores and various end groups (R = H, Me, CMe
2
,
Interestingly, while two Ant26Me or Np26Me molecules are CMe
3
) (Fig. S9–S12, ESI†). In the NMR spectrum of a CB
capable of complexing three CB[8] macrocycles, a single long- complexation, protons residing inside the centre of the CB
axis molecule can only form a pseudo[1,2]rotaxane with two cavity typically exhibit an upfield chemical shift of ca. 1 ppm,
CB[7] macrocycles binding at the tolyl ends (Fig. 2b and Fig. S7, while protons located outside and proximate to the CB portals
2
6
ESI†) and is not able to complex three macrocycles even in the will display downfield shifts. It is thus possible to determine
presence of a large excess of CB[7]. This indicates that the the precise binding site by comparing proton chemical shifts
stacking of two long-axis molecules must result in a discrete before and after complexation with CB. Np14R -CB[7] com-
1 2
entity that is considerably longer than its single molecule plexes are perfect for such analysis as CB[7] macrocycles in
component. A molecular dynamics (MD) simulation demon- these systems are relatively static on the NMR timescale. The
strates that the two long-axis molecules are actually stacked on 1,4-naphthyl moiety does not allow for shuttling of CB[7] across
1
7
top of one another with a slippage angle smaller than 901 the central core. Furthermore, the tolyl end group possesses a
resulting in only a partial overlap. As shown in Fig. 3, a 9,10- perfect shape to trap CB[7] with an energy barrier larger than
anthracenyl (Ant910Me) moiety is employed as the central core that in a typical methyl viologen-CB[7] complex, as shown in
in order to prevent the CB[n] from shuttling across the central Fig. 3a. Therefore, we are able to generate a profile by plotting
core (with a substantial energy barrier at z 4 1.5 Å). In a the change in chemical shift for each proton in Np14R,
1 2
Ant910Me -CB[7] complex, the minimum free energy appears enabling a direct visualisation of the binding sites for CB[7]
when moving the centre of the red highlighted phenyl moiety as shown in Fig. 4a. The dumbbell shape of each profile clearly
close to the centre of CB[7] (z = 0 Å). In a Ant910Me -CB[8]2 shows the binding position of each CB[7] along the axis
2
complex, by fixing the related position between one long-axis molecule, Np14R. It confirms that more bulky end groups
molecule and CB[8], a minimum energy is obtained only when generate larger central spacing.
the red highlighted phenyl moiety of the movable long-axis
molecule is placed slightly further away from the centre of core and bulkier end groups such as isopropyl (Ph14CMe
) were synthesised in order to check if
Several new long-axis molecules containing a 1,4-phenyl
2
)
CB[8] (z o 0 Å). This partial overlap in stacking of the two long- and tert-butyl (Ph14CMe
3
axis molecules leads to an elongated entity.
they form pseudo[2,3]rotaxanes even without an elongated
core. The 1,4-naphthyl moiety was not used in this case as
dimeric stacking of these cores is too large for simultaneous
inclusion in a CB[8] cavity. Additionally, a tert-butyl group is
too big to generate a dimeric entity with CB[8]. Instead, only
Fig. 3 Free energy profiles obtained from the adaptive biasing force (ABF)
2
4,25
method
COM) of CB[n] and the COM of the binding motif (a) for MV
dotted line, MV represents methyl viologen), MV -CB[8] (red dash-dotted
line), Ant910Me -CB[7] (blue dashed line), and Ant910Me -CB[8] (red
solid line). For Ant910Me -CB[7] (b), z is the COM spacing between one
phenyl moiety (highlighted in red) and CB[7] (green); while for Ant910Me
CB[8] (c), z is the COM spacing between the phenyl moiety of one long-
correlated to the distance z between the centre-of-mass
Fig. 4 Profiles established from the change in chemical shift of Np14R
(
1
-CB[7] (blue
1
2 3
(R = H, Me, CMe , CMe ) upon complexation with CB[7] (a) showing
1
1
a central spacing determined by the size of the substituent R group.
1
1
2
2
2
H-NMR spectra for (b) Ph14CMe
2 1 2
(G), (c) G -CB[7] with excess CB[7],
1
2
and (d) G -CB[8] at 298 K. Concentrations of G for all species are 60 mM.
2
3
2
-
The blue and red profiles in (a) are plotted to highlight the chemical
shift change for protons above and below the long-axis molecules,
respectively. Specific values can be found in Fig. S9–S12 (ESI†).
2
axis molecule (highlighted in red) and CB[8] (green).
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pseudo[1,2]rotaxanes or pseudo[1,1]rotaxanes are observed in a Conflicts of interest
3
mixture of 1 equiv. Ph14CMe with 2 equiv. or 1 equiv. CB[8],
respectively (Fig. S13, ESI†). However, a pseudo[2,3]rotaxane
There are no conflicts to declare.
was successfully fabricated when using Ph14CMe as the long-
2
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