A Redox-Switchable Molecular Zipper

Article abstract of DOI:10.1021/jacs.9b09756

The design and synthesis of artificial molecular switches (AMSs) displaying architectures of increased complexity would constitute significant progress in meeting the challenging task of realizing artificial molecular machines (AMMs). Here, we report the

Full text of DOI:10.1021/jacs.9b09756

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Article
A Redox-Switchable Molecular Zipper
Melissa Dumartin, Mark C. Lipke, and J. Fraser Stoddart
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b09756 • Publication Date (Web): 11 Oct 2019
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A Redox-Switchable Molecular Zipper
Melissa Dumartin,† Mark C. Lipke*,‖ and J. Fraser Stoddart*,†,§, ‡
†Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United
States
ǁ Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 610 Taylor
Road, Piscataway, New Jersey 08854, United States
§Institute of Molecular Design and Synthesis, Tianjin University, 92 Weijin Road, Nankai District, Tianjin,
300072, P. R. China
‡School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia
*E-mail: stoddart@northwestern.edu
*E-mail: ml1353@chem.rutgers.edu
MAIN TEXT
*Correspondence Address
*Correspondence Address
Professor J. Fraser Stoddart
Department of Chemistry
Northwestern University
2145 Sheridan Road
Doctor Mark C. Lipke
Department of Chemistry and
Chemical Biology, Rutgers
The State University of NJ
610 Taylor Road
Evanston, IL 60208 (USA)
Tel : (+1)-847-491-3793
Email: stoddart@northwestern.edu
Piscataway, NJ 08854 (USA)
Email: ml1353@chem.rutgers.edu
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ABSTRACT: The design and synthesis of artificial molecular switches (AMSs) displaying
architectures of increased complexity would constitute significant progress in meeting the
challenging task of realizing artificial molecular machines (AMMs). Here, we report the synthesis
and characterization of a molecular shuttle composed of a cyclobis(paraquat-4,4′-biphenylene)
cyclophane ring and a dumbbell incorporating a cyclobis(paraquat-m-phenylene) cyclophane
‘head’ and a bifurcated, tawse-like, ‘tail’ composed of two oligoether chains, each containing a
1,5-dioxynaphthalene ring. In its reduced state the ring-in-ring recognition motif, between the meta
and para bisradical dicationic cyclophanes (rings) defines the [2]rotaxane, whereas in the oxidized
state, the cyclobis(paraquat-4,4′-biphenylene) cyclophane encircles the two 1,5-dioxynaphthalene
rings in the bifurcated ‘tail’. The redox-controlled molecular shuttling, which can be likened to the
action of a zipper in the macroscopic world, exhibits slow kinetics dampened by the opening and
closing of the bifurcated ‘tail’ of the molecular shuttle. Cyclic voltammetry reveals that this slow
shuttling is associated with electrochemical hysteresis.
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■ INTRODUCTION
Ever since the first redox-switchable molecular shuttle was reported1 in 1994, the mechanical
bond2 has provided the literature with a plethora of molecular switches.3 Taking advantage of the
constraint imposed by the mechanical link, such mechanically interlocked molecules (MIMs) have
been found to display unique chemical,4 physical5 and electronic properties.6 Although bistable
rotaxanes are frequently referred to7 as potential AMMs, there are very few examples of rotaxane-
based molecular machines8 capable of performing work at the single-molecule level. ‘Machine-
like’ characteristics have been reached by rotaxane-based molecular muscles9 in which large-
amplitude contractile motions10 were achieved successfully in response to an external stimulus. In
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recent years, strategies have emerged11 for scaling up these motions by incorporating the AMSs
within materials. Sophisticated supramolecular polymers made of repeating units of rotaxane-
based molecular muscles ‒ i.e., daisy chains ‒ have been reported in the literature12 that induce
macroscopic responses in bulk materials ‒ i.e., sol-gel transitions, gel actuators, etc. ‒ upon
expansion or contraction of the individual AMSs. Designing new classes of materials, based on
redox-active rotaxanes, is nowadays of considerable interest because of the increasing demand for
smart responsive materials, offering the advantage of bulk physical properties that can be altered
either chemically or electrochemically.
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Rotaxanes utilizing various redox-driven switches, such as those incorporating redox-active
donor‒acceptor recognition motifs, metallo-mechanomolecules and redox-tunable hydrogen-
bonds have been reported13 in the literature. In particular, the recent harnessing14 of radical-pairing
interactions to form strong inclusion complexes between the cyclobis(paraquat-p-phenylene)
radical cation (CBPQT2(+•)) and viologen derivatives (V+•) ([MV⊂CBPQT]3(+•): Ka (MeCN, ITC)
= (5.04 ± 0.63) × 104 M‒1, MV refers to methyl viologen)15 led to the emergence of radical-
template directed strategies16 for synthesizing MIMs. Recent efforts toward expanding this binding
motif led17 to the discovery of a relatively strong 1:1 host–guest complex ([m-CBPQT⊂MS]4(+•)
:
Ka (MeCN, UV‒Vis‒NIR) = (1.12 ± 0.08) × 105 M‒1) between a square-shaped bisradical
dicationic cyclobis(paraquat-4,4′-biphenylene) (MS2(+•)) and a smaller m-xylylene-linked isomer
of CBPQT2(+•), namely, the bisradical dicationic m-CBPQT2(+•). This ring-in-ring complex
displays promising features for applications in AMSs and AMMs: it alternates between strong
association in its reduced state and strong repulsion in its oxidized state and, furthermore, exhibits
relatively slow kinetics of association and dissociation. A ring-in-ring [2]rotaxane (BBRn+)
incorporating the [m-CBPQT⊂MS]4(+•) recognition motif by including m-CBPQT2(+•) in its
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dumbbell component was found18 (Figure 1a) to conserve these features, as indicated by
electrochemical hysteresis for switching between states with highly distinct electronic properties.
Utilizing this ring-in-ring recognition motif, we have designed a rotaxane Zip-Rn+ which operates
by the shuttling motion of the MSn+ cyclophane19 between two recognition sites — one stabilized
by radical-pairing in its reduced state (Zip-R4(+•)) and the other (Zip-R8+) stabilized by
π‒donor/π‒acceptor interactions in its oxidized state. This [2]rotaxane was synthesized in two parts
— one part of the dumbbell incorporates m-CBPQT4+, while the second part consists of two
oligoether ‘tails’, each incorporating 1,5-dioxynaphthalene (DNP) rings and terminated by bulky
groups to prevent (Figure 1b) the dethreading of the MS4+ cyclophane. Upon oxidation, Coulombic
repulsion between the two tetracationic cyclophanes (i.e., MS4+ and m-CBPQT4+) obliges the MS4+
ring to move away from the electron poor bipyridinium units in the direction of the electron-rich
DNP rings in the two bifurcated strands, thereby forcing the two tawse-like ‘tails’ to come together
in a zip-like manner. Although [3]rotaxanes displaying two dumbbells encircled by one ring have
been reported in the literature,20 the uniqueness of this architecture resides in a single doubly
threaded dumbbell, thus affording a [2]rotaxane which constitutes a redox-controlled molecular
shuttle. The novelty of this MIM lies in its ability to couple long-range translational movement
with large-amplitude orthogonal expansion and contraction, commensurate with the permitted
branching and forced linearity of the ‘tails’ in a manner similar to the opening and closing of a
zipper — hence providing a fundamental basis for an alternative design for a molecular muscle. In
this paper we describe the synthesis and characterization of this redox-switchable molecular
zipper, as well as the differences in its properties associated with the Zip-R4(+•)/Zip-R8+ redox
states. Remarkably, the architectural singularity of this rotaxane — i.e., shuttling of the large
square-shaped cyclophane along the bifurcated tawse-like dumbbell — was found to feature
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similar, but more highly amplified, electronic properties than those displayed by other molecular
shuttles.
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■ RESULTS AND DISCUSSION
Radical templation, followed by in situ copper(I)-catalyzed azide–alkyne cycloaddition21
(CuAAC), was selected16c as a strategy for preparing Zip-R4(+•). This tetraradical tetracationic
[2]rotaxane is formed from a derivative of m-CBPQT2(+•) that bears, on one side, a bulky end
group to prevent MS2(+•) from slipping off the dumbbell, and on the other side, an azide group for
the cycloaddition. This functionalized cyclophane22 was obtained (Scheme S1) in four steps from
the known 4,6-dibromo-m-xylylene23 in a 20% overall yield. Notably, the two aryl groups do not
interfere with the macrocyclization step, which was achieved in similar yield (45%) to other m-
CBPQT∙4PF6 derivatives by employing pseudo-high-dilution conditions in refluxing MeCN. The
second molecular component used to form (Scheme 1) the dumbbell of Zip-R4(+•) is a half-
dumbbell alkyne derivative (HD-Alkyne), which was synthesized as depicted in Scheme S2 (see
SI) in four steps (overall yield: 36%) starting with 4-tris(4-tert-butylphenyl)phenol, which has
previously been employed24 as a stopper in rotaxanes.25
The Zip-R∙8PF6 rotaxane was obtained (Scheme 1) in a one-pot, two-step synthesis starting with
the formation of the inclusion complex [m-N3-Ar2-CBPQT⊂MS]4(+•) upon reduction of a 1:1 ratio
mixture of MS∙4PF6 and m-N3-Ar2-CBPQT∙4PF6 with copper powder in MeCN. The
(MeCN)4Cu+ formed as a byproduct catalyzes the cycloaddition between [m-N3-Ar2-
CBPQT⊂MS]4(+•) and the half-dumbbell, HD-Alkyne, added in a CH2Cl2/MeCN mixture (1:2).
The [2]rotaxane, initially obtained in its tetraradical tetracationic form, Zip-R∙4PF6, was oxidized
subsequently by exposure to air to afford Zip-R∙8PF6 in a 25% overall isolated yield after
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purification. H NMR spectroscopic monitoring of the reaction indicates that the [2]rotaxane is
formed with an in situ yield of 40% after 7 days at 30 °C while the dumbbell component (DB∙4PF6)
is formed in about 20% yield. The rest of the reaction mixture is composed of starting materials
that did not react after 7 days due to the very low solubility of the HD-Alkyne in MeCN. The
reaction time was not extended because of the degradation of the reagents after an extended period,
i.e., after 7 days. Thus, we estimate that ca 15% of the rotaxane was ‘lost’ during the multiple steps
of purification, which included solvent washes, reverse phase chromatography, and salt metathesis.
Mass spectrometry confirmed the identity of the [2]rotaxane as shown (Figure S3) in the SI.
The [m-N3-Ar2-CBPQT⊂MS]4(+•) inclusion complex was characterized by UV‒Vis‒NIR (Figure
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S4) and H NMR spectroscopy (Figure S25). An electronic absorption band characteristic of
radical-pairing was observed at 958 nm, very close to the NIR band observed17 for the [m-
CBPQT⊂MS]4(+•) inclusion complex (λmax = 941 nm). Such an intense NIR absorption band (Abs
= 0.44 at 0.06 mM in MeCN) is evidence of the formation of a relatively strong tetraradical
tetracationic complex. Crystals of [m-N3-Ar2-CBPQT⊂MS]4(+•) were obtained by vapor diffusion
i
of Pr2O into a solution of MS∙4PF6 (1 eq) and m-N3-Ar2-CBPQT∙4PF6 (1 eq) in MeCN after
reduction to their radical states using zinc dust, allowing us to obtain (Figure 2 and S1) the solid-
state superstructure of this inclusion complex. The formation of the 1:1 host–guest complex
revealed an ideal distance (3.2 Å) for radical-pairing interactions between the eclipsed
bipyridinium units in the host (MS2(+•)) and the bipyridinium units present in the guest (m-N3-Ar2-
CBPQT2(+•)). In comparison with the crystal structure that was obtained17 for the [m-
CBPQT⊂MS]4(+•) inclusion complex, the bipyridinium units of the inner and outer cyclophanes
are oriented perpendicularly, i.e., close to the orientation that would provide26 maximum overlap
of the SOMOs  orbitals.
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The mechanically interlocked nature of the [2]rotaxane was revealed by the 1H (Figure 3a), DOSY
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(Figures S14‒S15), C (Figure S16) and 2D correlated (Figures S17‒S20) NMR spectra of the
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Zip-R∙8PF6 in CD3CN. The resonances associated with the DNP protons (H24, H26 and H28/28’), are
shifted dramatically upfield to the region 4.30‒5.75 ppm, confirming (Figure 3a) that the electron
deficient cyclophane is encircling the electron rich DNP units. Although the multiplicity and the
number of resonances cannot be resolved at room temperature for H24 and H26, we observed two
doublets (   and 4.52 ppm) which can be assigned to the protons H28 and H28’. We presume
that these protons give rise to the most upfield shifted of the resonances as a result of [C‒H···π]
interactions with the 4,4′-biphenylene units of the MS4+ cyclophane. The ability of the electron
deficient MS4+ cyclophane to encircle two 1,5-dioxynaphthalene (DNP) units bounded by
polyether loops thus forming a ring-in-ring complex has been reported previously by Forgan et
al..27 [π···π], [C‒H···π] and [C‒H···O] interactions were found to be involved in the complex
formation.28 Although indications of the formation of such interactions could not be observed in
the NOESY spectrum (Figure S19), the ROESY spectrum displayed the expected spatial
correlations (Figure S20) for the MS4+ cyclophane encircling the DNP units. Indeed, the
resonances associated with the interlocked cyclophane protons (H2, H15, H8, H9 and H25) showed
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spatial correlations with the oligoether protons and the DNP protons, namely, H24, H26 and H28/28’
.
Hence, we are of the opinion that the formation of the donor‒acceptor recognition motif within the
Zip-R8+ is driven by a combination of [π···π], [C‒H···π] and [C‒H···O] interactions.
The synthesis (see SI) and NMR spectroscopic characterization (Figures S9‒S10) of the
dumbbell29 were carried out to provide the reference chemical shifts for the dumbbell component
1
of the rotaxane. Comparing the H NMR spectrum of the Zip-R∙8PF6 with that of its dumbbell
(Figure 3e) provides clear evidence of the mechanically interlocked nature of the [2]rotaxane with
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characteristic DNP proton resonances obtained for H24/26/28 of the dumbbell, in contrast to the
upfield resonances observed for these protons in the rotaxane. As expected, the resonances of the
smaller cyclophane within Zip-R∙8PF6 and its dumbbell are comparable to the resonances (Figure
3b) of m-N3-Ar2-CBPQT∙4PF6, except for H5 and H17, which are shifted downfield on the account
of their proximity to the triazole group.
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Variable temperature 1H NMR spectra which were recorded (Figure S13) for Zip-R∙8PF6 between
293 and 338 K revealed a resonance for H15 that, at lower temperatures, overlaps with the aromatic
protons of the stoppers (H13/14). Likewise, the signal for H11 was confirmed as overlapping with
the resonances for H10/12. Increasing the temperature also provided evidence for the assignment of
the protons (H19, H20, H29) on the para-substituted m-xylylene linker. Indeed, those protons are
subjected to shielding induced by the shuttling of the MS4+ cyclophane that is favored at high
temperature. The proton resonances (H24, H26, H28/28’) associated with the DNP units exhibit
selective broadening at 338 K, and are significantly shifted downfield compared to the
corresponding proton signals in the spectrum collected at 293 K. We assume that higher
temperatures also favor the rotation of MS4+ around the DNP units along with enhanced
movements of the polyether chains, presumably causing the loss of the [C‒H···O] interactions.
This hypothesis is supported by the downfield shift and broadening of the bipyridinium proton H15
resonance, which is possibly involved in [C‒H···O] interactions.
1
The characterization of Zip-R∙4PF6 was also carried out by H NMR spectroscopy (Figure 4a),
taking advantage of our recent observation17 that tetraradical tetracationic ring-in-ring complexes
1
possess singlet electronic ground states which, at low enough temperatures, permit18, 30 their H
1
NMR characterization as diamagnetic organic species. H NMR spectra were recorded after
reduction of Zip-R∙8PF6 with zinc dust in CD3COCD3, stirring at room temperature for 10 min to
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afford complete conversion to Zip-R4(+•). The shuttling of the cyclophane away from the DNP
recognition units explains why the resonances (Figure 4a) attributed to the protons H24/26/28 were
found at typical chemical shifts for DNP protons (7.8–6.9 ppm), consistent with the resonances
observed (Figure 3e) for the DNP protons in the dumbbell. Most of the resonances expected for
Zip-R4(+•) can be observed at 25 °C in CD3COCD3, apart from signals expected for the radical
ring-in-ring portion of the rotaxane. As with other tetraradical tetracationic ring-in-ring complexes
and superstructures, decreasing the temperature, in this case to 218 K, allows the full spectrum to
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be visualized. Accordingly, H NMR spectra (Figure 4b) were recorded at several temperatures
between 298 and 218 K. The resolution of broad signals into individual resonances allowed us to
propose an assignment for each signal in the spectrum. It is worth noting that the solid-state
superstructure (Figure 2) of the [m-N3-Ar2-CBPQT⊂MS]4(+•) complex revealed long range
[C‒H···π] interactions (d = 4.4 and 4.6 Å) between the protons H6/7 and the π‒faces of the bitolyl
units of the MS2(+•) cyclophane. Consistent with these interactions being conserved in solution, the
resonances of the innermost bipyridinium protons H6 and H7 are shifted upfield dramatically so to
the region 3.8–3.6 ppm. Although these resonances overlap with the broad collection of resonances
associated with the aliphatic protons H30-41, integration of this region confirmed the presence of
signals for H6 and H7. This observation was supported by the direct observation of the expected
signals (Figure S25) between 3.8–3.5 ppm for the [m-N3-Ar2-CBPQT⊂MS]4(+•) complex. By
comparison with the geometry of the complex, it is to be expected within the rotaxane, that the
bipyridinium protons H2 and H2’ are the least shielded within the recognition motif and were
assigned to the most downfield new resonances at 8.0–8.1 ppm. The resonance observed at 5.7
ppm can be assigned to H15, shifted upfield on account of the shielding provided by the
bipyridinium units of the inner cyclophane. The selective broadening of the cyclophane resonances
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at 25 °C has been attributed18 previously to a thermally accessible triplet state at room temperature
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and was supported17 by DFT calculations on [m-CBPQT⊂MS]4(+•)
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UV‒Vis‒NIR spectroscopy (Figure 5a) was used to probe the conversion between the Zip-R8+ and
Zip-R4(+•). The reduction of Zip-R8+ was conducted in MeCN using zinc dust, and the resulting
Zip-R4(+•) displays a characteristic NIR band centered on 958 nm for the bipyridinium radical-
pairing. The reversibility of the interconversion between Zip-R8+ and Zip-R4(+•) upon chemical
reduction/oxidation was also followed by 1H NMR spectroscopy. Spectra were recorded (Figure
S26) for the switch between Zip-R8+ and Zip-R4(+•), followed by the oxidation back to Zip-R8+ in
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air. The final H NMR spectrum for the re-oxidized species, recorded without any purification,
shows a recovery of more than 95% of the Zip-R8+ with a minimal amount (5%) of degradation
when compared with the initial spectrum. The interconversion between the redox states was
investigated in more details by cyclic voltammetry. The cyclic voltammogram (CV) of Zip-R∙8PF6
recorded (Figure 5b) at 100 mV/s with ferrocene as an internal standard displayed three redox
states — (i) the octacationic rotaxane (Zip-R8+), (ii) the tetraradical tetracationic rotaxane (Zip-
R4(+•)) and (iii) the neutral form of the rotaxane (Zip-R0). Both Zip-R4(+•)/Zip-R0 and Zip-R8+/
Zip-R4(+•) redox couples exhibit non-trivial profiles with multiple waves or shoulders associated
with each interconversion. The consistency of the CVs over several cycles suggests that switching
between the three redox states is reversible chemically, as expected since the mechanically
interlocked nature of the molecule prevents dissociation of the components.
The oxidation of Zip-R4(+•) to Zip-R8+ gives rise (Figure 6a) to two oxidation waves at a scan rate
of 100 mV/s, suggesting the occurrence of slow dynamic processes that were investigated further
at scan rates of 20–10,000 mV/s. In order to reduce interference from electrode fouling, a low
concentration of the analyte was used, resulting in relatively small current peaks that were,
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nevertheless, well-defined when the capacitive current was subtracted from the CVs. The redox
couple exhibits a large peak separation with a single, yet different, oxidation wave observed at
both high scan rates (10,000 mV/s with ΔEp = 140 mV and Eox1 = ‒0.66 V) and low scan rates (20
mV/s with ΔEp = 140 mV and Eox2 = ‒0.55 V), while the two oxidation waves are observed when
scan rates between 100–1000 mV/s are employed. It is worth noting that the dumbbell component
redox couple exhibits (Figure S27b) a single reversible redox wave at scan rates between 5–5000
mV/s, suggesting that the splitting of the oxidation waves of Zip-R8+ arises from the dynamics of
the mechanically interlocked components. A unique reduction wave was observed for Zip-R8+
regardless the scan rate applied, though increasing the scan rate broadens this peak and shifts it
towards more negative potentials (Ered = ‒0.80 V for Zip-R∙8PF6 at 10,000 mV/s). Meanwhile,
when low scan rates are applied (Ered = ‒0.69 V for Zip-R∙8PF6 at 20 mV/s), the reduction wave
appears sharper and more positive, indicating stabilization of the radical state upon the formation
of the ring-in-ring recognition motif. Assuming that the rotaxane undergoes two-electron redox
processes — like the individual cyclophanes — we postulate that the innermost cyclophane is the
first to be reduced (Ered = ‒0.74 V for MS∙4PF6 and Ered = ‒0.71 V for the dumbbell DB∙4PF6 at
200 mV/s), thus affording (Figure 6b) the intermediate Zip-R(6+)(2•)D. It is to be expected that the
electron rich surroundings of MS4+ within the Zip-R(6+)(2•)D will result in its stabilization towards
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reduction, shifting the required potential for reduction to the Zip-R4(+•) state to more negative
D
potentials compared to that required for reduction of the free cyclophane. At slower scan rates,
equilibration to the more stable Zip-R4(+•) state occurs quickly enough to cause the reduction
A
wave to be shifted towards positive potentials while, at rapid scan rates, there is less time for the
two cyclophanes in either the Zip-R(6+)(2•)D or Zip-R4(+•)D intermediates to associate, resulting in a
more negative and broadened reduction wave, corresponding to the complete reduction to the Zip-
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R4(+•) metastable co-conformation. Furthermore, applying intermediate scan rates led to the
D
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observation of two waves of oxidation which display different ratios. Increasing the scan rate
induces a decrease of the initially unique oxidation wave at ‒0.55 V (20 mV/s), while another
oxidation wave at a more negative potential (Eox1 = ‒0.65 V) arises and becomes the predominant
oxidation wave at scan rates ≥ 1,000 mV/s. The more positive oxidation wave presumably
corresponds to the presence of an electronically stabilized ground state co-conformation Zip-
R4(+•)A, which has time to form fully at low scan rates, while the more negative oxidation wave
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corresponds to the metastable co-conformation Zip-R4(+•) that does not have time to convert to
D
the ground-state co-conformation at rapid scan rates. It is worth noting that the very slow scan-rate
regime allows observation (Figure S29) of Zip-R8+/ Zip-R4(+•) interconversion as a quasi-
reversible process (5 mV/s with ΔEp = 100 mV).
The CVs of Zip-R8+ indicate similar switching dynamics to those previously observed18 for the
‘Box-in-Box’ Rotaxane (BBR8+ in Figure 1a), which were attributed to a combination of (i) the
slow rate of the MS2(+•) cyclophane encircling the smaller m-CBPQT2(+•) cyclophane that results
from strong charge repulsion and the tight fit of the ring-in-ring recognition motif, and (ii) the
strong association of the two cyclophanes in the doubly radically paired state which causes them
to dissociate slowly unless electrons are first removed.
Qualitative comparison of the CVs of BBR∙8PF6 and Zip-R∙8PF6 revealed that the rate constant
(k1) for the association of the cyclophanes in Zip-R4(+•) is much lower than for the analogous
D
process in BBR4(+•)D. In particular, the appearance (Figure S33) of an oxidation wave for the
metastable co-conformation occurs18 at a lower scan rate for the molecular zipper (50 mV/s for
Zip-R4(+•)D, versus 1,000 mV/s for BBR4(+•)D), and likewise, the oxidation wave attributed to the
ground-state co-conformation disappears almost entirely at 10,000 mV/s for Zip-R8+ but is still
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weakly observable for BBR8+ at a scan rate of 50,000 mV/s. Considering that Zip-R∙8PF6 and
BBR∙8PF6 appear to exhibit similar mechanisms of switching, but at different rates, the CV data
for Zip-R8+ was examined using computational fitting of simulated CVs to the experimental data
based on the mechanism depicted in Figure 6b. The CVs collected at 200 mV/s and 1,000 mV/s
were matched with simulated CVs (Figures S36‒S37), resulting in good agreement between
experimental and simulated data for k1 values of 0.23 s‒1 and 0.56 s‒1, respectively. These
matchings, however, produced k2 values (8.2 s‒1 and 6.94 s‒1) that are larger than the k1 values,
which is unrealistic considering the higher charge repulsion between the cyclophanes in the Zip-
R(6+)(2•) state compared with the Zip-R4(+•) state, which should render association of the
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cyclophanes faster for the tetraradical tetracationic state than for the bisradical hexacationic state.
Thus, simulations of the CVs between 20 and 10,000 mV/s were also performed with manual
variation of the k1 value, while keeping k2 ≤ k1 and k‒1 << k1 to ensure that the results are
chemically reasonable. Values of k1 = 1.2 s‒1, k‒1 = 0.008 s‒1, k2 = 0.8 s‒1, and k‒2 = 35 s‒1 provided
(Figures S34‒S35) simulated CVs that showed good agreement with the experimental data,
particularly with respect to the first appearance of the oxidation wave of Zip-R4(+•) at 50 mV/s
D
and the disappearance of the oxidation wave of Zip-R4(+•)A at 10,000 mV/s. These results indicate
that the conversion of Zip-R4(+•) to Zip-R4(+•) occurs at one to two orders of magnitude more
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A
slowly (k1 ≈ 0.23–1.2 s‒1) than the corresponding process for converting BBR4(+•)D to BBR4(+•)
A
(k1-BBR ≈ 10–25 s‒1, Figure 6c). The decreased rate of association of the two cyclophanes in Zip-
R4(+•)D can be attributed to hindered shuttling of the MS2(+•) cyclophane across the double-stranded
dumbbell, which is to be expected, based on the entropically unfavorable requirement that the two
strands of the dumbbell become press together to enable passage of the tightly fitting outer
cyclophane.
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In view of the CV data collected for this molecular zipper, electrochemical hysteresis was revealed.
The ideal size complementarity displayed by the ring-in-ring recognition motif, while providing
for strong binding of the cyclophanes once they are overlapped, imposes a steric constraint upon
their initial association, resulting in slow kinetics of association and dissociation for both the Zip-
R8+ and the BBR8+. The structural features of the molecular zipper provoke an even more
exaggerated electrochemical hysteresis for the switching between Zip-R8+ and Zip-R4(+•), as
revealed by an even slower rate constant for the association of the two cyclophanes in the
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metastable co-conformation Zip-R4(+•) when forming the ground-state co-conformation Zip-
D
R4(+•)
.
A
■ CONCLUSIONS
In summary, we have reported the synthesis of an octacationic bistable [2]rotaxane, based on a
ring-in-ring radical-radical templation motif, and demonstrated that this mechanically interlocked
molecule with a doubly threaded dumbbell containing 1,5-dioxynaphthalene rings, incorporated
within oligoether chains terminated by stoppers, displays a mechanical-like motion — reminiscent
of zippering — that can be redox driven. This molecular zipper exhibits slow kinetics associated
with the redox-driven switching of a ring between two different recognition sites on a bifurcated,
tawse-like, dumbbell. The slow kinetics of the redox-driven switching reflect the rigid
preorganization of the tetraradical tetracationic ring-in-ring recognition motif and the steric and
electronic constraints associated with the opening and closing of the doubly stranded dumbbell
component. The large-amplitude motion, which accompanies switching, could result in large
conformational changes if the switches were to be embedded in polymeric chains rather than in
the relatively short ‘tails’ of a doubly stranded dumbbell. We envisage that this molecular zipper
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could be useful in the late-stage functionalization of polymers and, in so doing, provide an efficient
route to the construction of mechanical actuators.
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■ ASSOCIATED CONTENT
Supporting Information
The Supporting Information includes experimental details, including synthesis, crystal data, mass
spectrometry, NMR and UV‒Vis‒NIR spectra and CV supportive figures. This material is
available free of charge via the Internet at http://pubs.acs.org.
■ AUTHOR INFORMATION
Corresponding Authors
*stoddart@northwestern.edu
*ml1353@chem.rutgers.edu
Notes
The authors declare no competing financial interest.
■ ACKNOWLEDGEMENTS
This research is part of the Joint Center of Excellence in Integrated Nano-Systems (JCIN) at King
Abdulaziz City of Science and Technology (KACST) and Northwestern University (NU). The
authors would like to thank both KACST and NU for their continued support of this research.
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S.; Botros, Y. Y.; Stoddart, J. F., Symbiotic Control in Mechanical Bond Formation. Angew. Chem.,
Int. Ed. 2016, 55, 12387–12392.
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(17) Lipke, M. C.; Cheng, T.; Wu, Y.; Arslan, H.; Xiao, H.; Wasielewski, M. R.; Goddard, W. A.;
Stoddart, J. F., Size-Matched Radical Multivalency. J. Am. Chem. Soc. 2017, 139, 3986–3998.
(18) Lipke, M. C.; Wu, Y.; Roy, I.; Wang, Y.; Wasielewski, M. R.; Stoddart, J. F., Shuttling Rates,
Electronic States, and Hysteresis in a Ring-in-Ring Rotaxane. ACS Cent. Sci. 2018, 4, 362–371.
(19) When referred to as part of the [2]rotaxane, the cyclophanes names are not highlighted in
bold.
(20) (a) Klotz, E. J. F.; Claridge, T. D. W.; Anderson, H. L., Homo- and Hetero-[3]Rotaxanes with
Two Π-Systems Clasped in a Single Macrocycle. J. Am. Chem. Soc. 2006, 128, 15374–15375; (b)
Lee, C.-F.; Leigh, D. A.; Pritchard, R. G.; Schultz, D.; Teat, S. J.; Timco, G. A.; Winpenny, R. E.
P., Hybrid Organic–Inorganic Rotaxanes and Molecular Shuttles. Nature 2009, 458, 314–318; (c)
Cheng, H. M.; Leigh, D. A.; Maffei, F.; McGonigal, P. R.; Slawin, A. M. Z.; Wu, J., En Route to
a Molecular Sheaf: Active Metal Template Synthesis of a [3]Rotaxane with Two Axles Threaded
Through One Ring. J. Am. Chem. Soc. 2011, 133, 12298–12303.
(21) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B., A Stepwise Huisgen
Cycloaddition Process: Copper(I)-Catalyzed Regioselective “Ligation” of Azides and Terminal
Alkynes. Angew. Chem., Int. Ed. 2002, 41, 2596–2599.
(22) m-N3-Ar2-CBPQT∙4PF6 — See Scheme S1 (SI).
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(23) Shi, Y.; Suguri, T.; Dohi, C.; Yamada, H.; Kojima, S.; Yamamoto, Y., Highly Active
Catalysts for the Transfer Dehydrogenation of Alkanes: Synthesis and Application of Novel 7–
6–7 Ring-Based Pincer Iridium Complexes. Chem. – Eur. J. 2013, 19, 10672–10689.
(24) Ashton, P. R.; Ballardini, R.; Balzani, V.; Bělohradský, M.; Gandolfi, M. T.; Philp, D.; Prodi,
L.; Raymo, F. M.; Reddington, M. V.; Spencer, N.; Stoddart, J. F.; Venturi, M.; Williams, D. J.,
Self-Assembly, Spectroscopic, and Electrochemical Properties of [n]Rotaxanes. J. Am. Chem. Soc.
1996, 118, 4931–4951.
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(25) These stoppers are large enough to prevent the formation of a traditional [2]rotaxane, but, by
virtue of its size, MS4+ is able to slip over the side of HD-Alkyne by folding it in half to serve as a
half-dumbbell in a doubly-threaded rotaxane.
(26) Geraskina, M.; Dutton, A. S.; Juetten, M.; Wood, S.; Winter, A., The Viologen Cation Radical
Pimer: A Case of Dispersion-Driven Bonding. Angew. Chem., Int. Ed. 2017, 56, 9435–9439.
(27) Forgan, R. S.; Wang, C.; Friedman, D. C.; Spruell, J. M.; Stern, C. L.; Sarjeant, A. A.; Cao,
D.; Stoddart, J. F., Donor–Acceptor Ring-in-Ring Complexes. Chem. – Eur. J. 2012, 18, 202–212.
(28) In this work the authors26 demonstrate how those two rings can assemble into a ring-in-ring
complex (Ka (UV‒Vis) = 280 M‒1 in MeCN) driven by the formation of an
acceptor‒donor‒donor‒acceptor stack. It was found that in the solid-state the aromatic units of the
bitolyl moieties of the MS4+ cyclophane are involved in [C‒H···π] interactions with the protons
that are para to the oxygens (i.e., H28/28’) in the naphthalene units. In this previous example26, the
polyether loops reinforced complexation by the formation of [C‒H···O] interactions with the
protons of the bipyridinium units of the MS4+ cyclophane.
(29) Synthesis of DB∙4PF6 is depicted in SI (page S15).
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(30) Cai, K.; Lipke, M. C.; Liu, Z.; Nelson, J.; Cheng, T.; Shi, Y.; Cheng, C.; Shen, D.; Han, J.-
M.; Vemuri, S.; Feng, Y.; Stern, C. L.; Goddard, W. A.; Wasielewski, M. R.; Stoddart, J. F.,
Molecular Russian Dolls. Nat. Commun. 2018, 9, 5275–5282.
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Scheme 1. Synthesis of the Zip-R·8PF6 rotaxane by radical templation and copper(I)-catalyzed
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cycloaddition.
Figure 1. Electrochemically driven actuation of: (a) the ‘Box-in-Box’ rotaxane (BBR4(+•)/BBR8+)
and (b) the molecular zipper (Zip-R4(+•)/Zip-R8+) — donor‒acceptor interactions underpin the
contracted state (Zip-R8+) and radical-pairing interactions underpin the extended state (Zip-R4(+•)).
Figure 2. X-Ray crystal structures of the complex: [m-N3-Ar2-CBPQT⊂MS]4(+•). The tetraradical
‒
tetracationic complex was crystallized as its PF6 salt — the counterions were omitted for the sake
of clarity. MS2(+•) is shown in blue and m-N3-Ar2-CBPQT2(+•) in purple. a) View of the [m-N3-
Ar2-CBPQT⊂MS]4(+•) with the bipyridinium units of m-N3-Ar2-CBPQT2(+•) aligned
perpendicular to the page.b) Eclipsed view of the [m-N3-Ar2-CBPQT⊂MS]4(+•) and representation
of the long range [C‒H···π] interactions (distances measured from the carbon atom — CH — to
the center of the aromatic ring). c) View of the [m-N3-Ar2-CBPQT⊂MS]4(+•) with the
bipyridinium units of MS2(+•) aligned perpendicular to the page. d) View of the [m-N3-Ar2-
CBPQT⊂MS]4(+•) with the planes of all four bipyridinium units aligned parallel with the page.
Figure 3. 1H NMR Spectra at 298 K (500 MHz, CD3CN): (a) Zip-R·8PF6 (2.14 mM). Partial spectrum:
9.0–3.2 and 1.5–1.0 ppm, (b) m-N3-Ar2-CPBQT·4PF6, (c) MS·4PF6, (d) Zip-R·8PF6 and (e) DB·4PF6.
Partial spectra: 9.0–3.5 ppm.
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Figure 4. 1H NMR (600 MHz, CD3COCD3) spectrum characterization of the Zip-R∙4PF6 (2.2 mM): (a)
Partial spectrum (9.0–3.5 and 1.5–1.2 ppm) at 298 K. (b) Partial spectra (9.0–3.5 ppm) collected over a
temperature range of 298‒218 K.
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Figure 5. Reversible switching between the redox states: Zip-R4(+•) and Zip-R8+: (a) UV‒Vis‒NIR spectra
of the Zip-R·8PF6 (0.035 mM) and Zip-R∙4PF6 (0.030 mM) at 298 K in MeCN. (b) CV of the Zip-R·8PF6
in a 0.1 M [Bu4N]|[PF6] MeCN electrolyte solution (0.13 mM) recorded at 100 mV/s at 298 K. The current
was normalized, and the potentials referenced to ferrocene as an internal standard.
Figure 6. Zip-R8+ / Zip-R4(+•) Interconversion: (a) CVs of Zip-R∙8PF6 (0.05 mM) in a 0.1 M [Bu4N]|[PF6]
MeCN electrolyte solution at various scan rates (20‒10,000 mV/s) with a potential window that includes
only the Zip-R8+ and Zip-R4(+•) states of the rotaxane. The current was normalized and the potentials were
referenced to ferrocene as an internal standard. The CVs of the electrolyte in the absence of redox-active
analytes were substracted from the raw data at each scan rate, and the original CVs are provided in Figures
S31‒S32. (b) Proposed mechanism for the Zip-R8+/Zip-R4(+•) interconversion. A stands for associated, D
stands for dissociated. (c) Schematic representation of the BBR4(+•)D/BBR4(+•)A equilibrium.
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