Orthogonal switching of self-sorting processes in a stimuli-responsive library of cucurbit[8]uril complexes

Article abstract of DOI:10.1039/c7cc05469f

The self-sorting processes in dynamic libraries of cucurbit[8]uril complexes can be switched in an orthogonal way by external stimuli. Protonated phenylpyridine guests form a 2:1 homoternary π-donor-π-acceptor complex, while deprotonation makes it a partner for ethylviologen in a 1:1:1 heteroternary complex. Reduction of the viologen instead generates a 2:1 homoternary complex of viologen radical-cations.

Full text of DOI:10.1039/c7cc05469f

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ARTICLE
Orthogonal switching of self-sorting processes in a stimuli-
responsive library of cucurbit[8]uril complexes†
Received 00th January 20xx,
Accepted 00th January 20xx
Stefan Schoder and Christoph A. Schalley*
DOI: 10.1039/x0xx00000x
www.rsc.org/
The self-sorting processes in dynamic libraries of cucurbit[8]uril of the chemical system. Kim and co-workers reported a three-
complexes can be switched in an orthogonal way by external way supramolecular switch composed of viologen and
stimuli. Protonated phenylpyridine guests form a 2:1 homo- tetrathiafulvalene, based on the redox-controlled, highly
ternary
-donor--acceptor complex, while deprotonation selective interconversion between hetero- and homo-guest
makes it a partner for ethylviologen in a 1:1:1 heteroternary pairs.15 Scherman et al. used redox-switchable viologen in
complex. Reduction of the viologen instead generates 2:1 combination with a photo-responsive azobenzene derivative
homoternary complexes of viologen radical-cation.
as the second binding partner.13c, 16 Reduction of the system
results in
a
redox-driven homoternary complex and
To construct functional (supra)molecular devices,1 supramole- photoexcitation in a light-driven “uncomplexed” state.
cular chemistry adopted many concepts that also control the Herein, we report a novel supramolecular system which
form and function of living systems such as molecular includes ternary complexes in every state. The self-sorting
recognition,2 templation,3 self-assembly,4 self-sorting,5 and network is based on cucurbit[8]uril, which complexes the pH-
multivalency.6 With these concepts of supramolecular responsive phenylpyridine derivative
P
,
redox-responsive
neutral, electron-rich naphthalene
N as the guests in water (Scheme 1).
synthesis, complex structures can be accomplished from viologen V2+ and
a
simple programmed building blocks through a bottom-up derivative
design strategy.7
Cucurbit[8]uril
The distinct feature of monocationic 4-phenylpyridinium
Q
as a macrocyclic host forms homo- and derivatives is the formation of 2:1 homoternary complexes.17 If
heteroternary complexes with various aromatic guests8 – e.g. this holds also true for protonated rather than methylated
with two viologen cation-radicals9 or with an electron-poor 4-phenylpyridinium, switching between a charged and a
guest such as a viologen dication and an electron-rich guest neutral state becomes possible by (de)protonation.
like dihydroxynaphthalene,10 respectively. It is thus a good Consequently, this guest becomes controllable by external
example for a host capable to induce self-sorting in complex stimuli. Scheme 1 summarizes the work presented here: All
mixtures by selecting either two identical copies of the same compounds used, the external stimuli, and the complexes
guest or two different guests that match with respect to their formed in the present work including previously described
electronic features.9-11 Beyond the mere self-sorting itself, complexes9-11 and the orthogonal switching of self-sorting
being able to switch the self-sorting processes with different processes are shown.
external and reversible stimuli provides control over the self-
Figure 1 shows 1H NMR spectra of neutral
P (a), protonated
sorting processes.12 Tuning the stimuli-responsiveness of these PH+ (b), and the 2:1 complex (PH+)2@Q (c) in D2O (for detailed
supramolecular switches in aqueous environment attracted signal assignments, see Fig. S5; ESI†). The complex exhibits a
significant interest over the last decades13 (including cascades well-defined, somewhat broadened set of signals with
with a series of sequentially added stimuli14). However, a significant complexation-induced signal shifts in agreement
major limitation is the combination of multiple stimuli to with those reported for the methylated analogue.18 Upon
obtain orthogonal control and thus more complex behaviour deprotonation, the signals of the free guest
P are observed
(Fig. 1d) suggesting the complete dissociation of (PH+)2@Q
.
The switching can also be observed by UV/Vis spectroscopy
a.S. Schoder, Prof. Dr. C. A. Schalley
Institut für Chemie und Biochemie, Freie Universität Berlin
Takustrasse 3, 14195 Berlin, Germany
E-mail: c.schalley@fu-berlin.de
†Electronic Supplementary Information (ESI) available: Complete experimental,
synthetic procedures and analytical data of new compounds, additional NMR, MS,
UV/Vis and fluorescence experiments. See DOI: 10.1039/x0xx00000x
and is fully reversible over several cycles (Fig. S6; ESI†).
Compound
emission at 418 nm upon excitation at 366 nm. The
corresponding cucurbituril complex (PH+)2@Q exhibits
P
is not fluorescent, but PH+ features a blue
a
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Scheme 1 Top left: Cucurbit[8]uril as the host and the guests used in this study together with the cartoons used to represent them; top right: (De)protonation of 4-phenylpyridine P
and reduction/oxidation of ethyl viologen V2+ as the two orthogonal external stimuli. Middle left: Complexes that form; middle right: Previously reported complexes.9-11 Bottom:
Stimuli-responsive self-sorting processes.
fluorescence red shift to 439 nm with a remarkable increase in superposition of the signals of the free guests (a,g), indicating
emission (Fig. S7 ESI†), which is in line with literature for the complete dissociation of (PH+)2@Q and PH+N@Q
.
1
similar phenylpyridinium derivatives.18 The equilibrium
Figure 2 shows the H NMR spectrum of a 2:1:1 mixture of
association constants for the (PH+)2@Q complex as PH+ V2+ and
, Q in acidic medium (c) (for details see Fig. S12,
determined by isothermal titration calorimetry (ITC) are K1 = ESI†), which clearly is a superposition of the spectra of V2+ and
1.66 x 107 M-1, K2 = 0.97 x 105 M-1 and K1 x K2 = 1.61 x 1012 M-2
(Fig. S8; ESI†) and agree well with those of the methylated
analogue.18 Complex (PH+)2@Q is also detected at m/z 969
(Fig. S9, ESI†) in the ESI mass spectra. However, this signal is
not very intense as charge repulsion leads to quick
fragmentation in the gas phase.
In analogy to the literature-known viologen-naphthalene
dimer complex V2+N@Q 10
,
a

-donor
forms in competition with (PH+)2@Q. Figure 1 shows
1H NMR spectra of the electron rich guest
(g) and the 3:1:2
mixture of PH+
and in acidic medium (e) (for details, see
-acceptor complex
PH+
-N
N
,
N
Q
Fig. S10, ESI†). Two sets of signals are observed, one for the
(PH+)2@Q complex described above and a second one for
PH+N@Q. The strong high-field shifts of the signals of
N
indicate its presence inside the cucurbituril cavity, where it
experiences the anisotropy of the aromatic rings of in close
analogy to the known complex V2+N@Q (Fig. S11, ESI†).
A confirmation of the formation of PH+N@Q by ESI-MS is
not possible because of the easy loss of the uncharged
P
Fig. 1 Partial 1H NMR spectra (700 MHz, 298 K, D2O, 1.0 mM) of (a) P, (b) PH+, a 2:1
mixture of PH+ and Q (c) in acidic (pH 4) and (d) in basic (pH 10) medium, (e) a 3:1:2
mixture of PH+, N and Q in acidic medium (pH 4; asterisks mark the newly formed
complex), (f) an equimolar mixture of PH+, N and Q in basic medium (pH 10), and (g) N;
DCl (35% in D2O) and K2CO3 were used to (de)protonate.
N
during the ionization process. After deprotonation, the region
of guest signals in the 1H NMR spectrum (f) matches the
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(PH+)2@Q. This is in agreement with the binding constants
determined for the possible complexes (PH+)2@Q and V2+@Q
,
already the first binding constant of PH+ to
Q
(K1 = 6.63 x
106 M-1) is higher than that of V2+ to
Q
(K = 1.1 x 105 M-1)9 by a
1
factor of about 60. The H NMR spectrum of the mixture after
deprotonation of PH+ shows a new set of signals (d), indicating
the formation of the 1:1:1 complex PV2+@Q. The signal at
6.75 ppm can be attributed to two different protons of
P and
one set of signals of the viologen protons is broadened (see
1H,1H COSY NMR Fig. S13, ESI†). The formation of PV2+@Q is
also confirmed by its characteristic charge-transfer band at
around 450 nm in the UV/Vis spectrum of the complex
(Fig. S14, ESI†). Again, the switching is fully reversible upon
protonation (Fig. S14, ESI†).
Fig. 3 UV/Vis spectra of (a) a mixture of V2+ and Q before and after reduction, (b) P, V2+
and Q before and after reduction with 10 equiv. Na2S2O4 (24 휇M V2+); in both cases
radical-cation dimer (V+)2@Q forms after reduction.
It is well known that viologen dications can be reduced to
the corresponding radical cations, which tend to dimerize
+
inside the cucurbituril cavity, yielding (V )2@Q (K2 = 2.0 x
Based on this simple library of complexes, a more complex
four-step self-sorting network was designed (Scheme 2) which
is responsive to redox and pH stimuli. The 2:1:1:2 mixture of
107 M-1).9 Formation of this complex is favoured over the
11b
charge-transfer complex V2+N@Q (K2 = 5.9 x 105 M-1).8,
PH+
,
V2+
,
N
and
Q
contains the two complexes (PH+)2@Q and
Consequently, it should be favoured over PV2+@Q as well,
V2+N@Q and corresponds to state
I
. The 1H NMR spectrum is a
considering the fact that
allows us to use redox chemistry as a stimulus in this system.
The reduction potential of cucurbituril complex V2+@Q (E1
N is more electron rich than P. This
superposition of the spectra of independently prepared
complexes and is shown in figure 4(b) (for details see Fig. S17,
ESI†). Deprotonation (d) gives state II with viologen-
naphthalene complex V2+N@Q still intact and the signals of
=
1/2
-0.58 V) was determined by cyclic voltammetry (CV) (Fig. S15,
ESI†). Neither the compounds
P
and PH+, nor complex
free
avoid formation of PV2+@Q a slight excess of
resulting in a set of signals for free . Subsequent reduction
P
indicate the complete dissociation of (PH+)2@Q. To
(PH+)2@Q are reduced under these conditions (Fig. S15, ESI†).
N
was used, thus
When sodium dithionite is used for chemical reduction of
+
+
viologen to its cation radical V the 2:1 complex (V )2@Q
forms as clearly indicated by the typical absorption bands at
541 nm (Fig. 3a) and 982 nm (Fig. S16, ESI†). The same bands
are observed when the literature-known charge-transfer
complex V2+N@Q and when independently prepared PV2+@Q
(Fig. 3b) are reduced. These results clearly indicate the
N
with Na2S2O4 results in the distinct UV/Vis absorption
+
spectrum (Fig. 4(g)) of complex (V )2@Q with the radical
cation viologen dimer inside the cucurbituril cavity (blue line).
P
and N in the mixture are not affected by the reduction as
shown by NMR experiments (Fig. S18, ESI†), so state III is
obtained. The reduction of the viologen in acidic medium is
possible, but subsequent reoxidation occurs rapidly. Hence,
the solution of state III was prepared with just a slight excess
of free protons (for procedure see Fig. S19, ESI†) and then
+
formation of (V )2@Q in both cases together with the release
of
N or P, respectively.
+
reduced, giving the unique absorption maxima of (V )2@Q
and therefore indicating state IV (red line). To demonstrate the
pH switching of the system between the reduced states III and
IV, the more oxidation stable state III was prepared and
Fig. 2 Partial 1H NMR Spectra (700 MHz, 298 K, D2O, 1.0 mM) of (a) P, (b) a 2:1 mixture
of PH+ and Q in acidic medium (pH 4), (c) a 2:1:1 mixture of P, V2+ and Q in acidic
medium (pH 4), (d) an equimolar mixture of P, V2+ and Q in basic medium (pH 10), (e)
an equimolar mixture of V2+ and Q forming V2+@Q, and (f) V2+; DCl (35% in D2O) and
K2CO3 were used to (de)protonate.
Scheme 2 Four step self-sorting square with two switches based on pH and redox with
state I to IV.
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Acknowledgements
View Article Online
DOI: 10.1039/C7CC05469F
We thank Dr Andreas Schäfer and the staff of the BioSupraMol
Core Facility at FU Berlin for recording the NMR spectra and
Hendrik V. Schröder for help with the CV measurements. We
are grateful for funding from the Deutsche Forschungs-
gemeinschaft (CRC 765).
Notes and references
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Fig. 4 Partial 1H NMR spectra (700 MHz, 298 K, D2O, 1.0 mM) of (a) (PH+)2@Q, (b) a
2:1:1:2 mixture of PH+, V2+, N and Q, (c) PV2+@Q, (d) a 2:1:1:2 mixture of P, V2+, N and
Q, (e) P, (f) N; (a) and (b) pH 4, (d) and (e) pH 10; DCl (35% in D2O) and K2CO3 were used
to (de)protonate; and (g) UV/Vis spectra of state III derived from reduction of state II
(blue), state IV derived from reduction of state I (red) and state IV derived from
acidification of state III (green) (24 휇M V2+); reducing agent is Na2S2O4.
8
9
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consecutive measurements over the span of two minutes (Fig.
S20, ESI†).
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and redox signals as the external stimuli. The new acid/base-
sensitive guest PH+ can form the 2:1 complex (PH+)2@Q. In
combination with the electron rich partner
N
it can form the
-acceptor complex PH+N@Q. In its deprotonated
P
can act as the electron rich counterpart to V2+, forming

-donor-
form,

-donor- P and
-acceptor complex PV2+@Q. Both compounds,
14 L. Cera and C. A. Schalley, Chem. Sci., 2014, 5, 2560-2567.
PH+, are electrochemical stable and, thus, allow an orthogonal
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+
16 F. Tian, D. Jiao, F. Biedermann and O. A. Scherman, Nat.
example of a cucurbituril-based self-sorting system which is
orthogonally switchable by pH and electrochemical inputs. The
high tolerance of this system is shown with a simple fully
controllable square network. This work is unique, as it is
possible to switch its self-sorting behaviour between the three
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ternary cucurbituril complexes (PH+)2@Q
,
PV2+@Q and
+
(V )2@Q
.
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