Diverse Proton-Conducting Nanotubes via a Tandem Macrocyclization and Assembly Strategy

Article abstract of DOI:10.1021/jacs.1c02789

Macrocycles that assemble into nanotubes exhibit emergent properties stemming from their low dimensionality, structural regularity, and distinct interior environments. We report a versatile strategy to synthesize diverse nanotube structures in a single, efficient reaction by using a conserved building block bearing a pyridine ring. Imine condensation of a 2,4,6-triphenylpyridine-based diamine with various aromatic dialdehydes yields chemically distinct pentagonal [5 + 5], hexagonal [3 + 3], and diamond-shaped [2 + 2] macrocycles depending on the substitution pattern of the aromatic dialdehyde monomer. Atomic force microscopy and in solvo X-ray diffraction demonstrate that protonation of the macrocycles under the mild conditions used for their synthesis drives assembly into high-aspect ratio nanotubes. Each of the pyridine-containing nanotube assemblies exhibited measurable proton conductivity by electrochemical impedance spectroscopy, with values as high as 10-3 S m-1 (90% R.H., 25 °C) that we attribute to differences in their internal pore sizes. This synthetic strategy represents a general method to access robust nanotube assemblies from a universal pyridine-containing monomer, which will enable systematic investigations of their emergent properties.

Full text of DOI:10.1021/jacs.1c02789

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Article
Diverse Proton-Conducting Nanotubes via a Tandem
Macrocyclization and Assembly Strategy
Michael J. Strauss, Manping Jia, Austin M. Evans, Ioannina Castano, Rebecca L. Li,
Xavier Aguilar-Enriquez, Emily K. Roesner, Jeremy L. Swartz, Anton D. Chavez, Alan E. Enciso,
J. Fraser Stoddart, Marco Rolandi,* and William R. Dichtel*
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ABSTRACT: Macrocycles that assemble into nanotubes exhibit
emergent properties stemming from their low dimensionality,
structural regularity, and distinct interior environments. We report
a versatile strategy to synthesize diverse nanotube structures in a
single, efficient reaction by using a conserved building block
bearing a pyridine ring. Imine condensation of a 2,4,6-
triphenylpyridine-based diamine with various aromatic dialdehydes
yields chemically distinct pentagonal [5 + 5], hexagonal [3 + 3],
and diamond-shaped [2 + 2] macrocycles depending on the
substitution pattern of the aromatic dialdehyde monomer. Atomic
force microscopy and in solvo X-ray diffraction demonstrate that
protonation of the macrocycles under the mild conditions used for
their synthesis drives assembly into high-aspect ratio nanotubes. Each of the pyridine-containing nanotube assemblies exhibited
measurable proton conductivity by electrochemical impedance spectroscopy, with values as high as 10−3 S m−1 (90% R.H., 25 °C)
that we attribute to differences in their internal pore sizes. This synthetic strategy represents a general method to access robust
nanotube assemblies from a universal pyridine-containing monomer, which will enable systematic investigations of their emergent
properties.
of excess acid, whereas lower acid concentrations accelerated
macrocycle hydrolysis.35,36 We subsequently identified a single
macrocycle based on pyridine-2,6-dicarboxaldehyde that was
assembled using sub-stoichiometric quantities of acid, giving rise
to robust assemblies that formed fibers with mechanical
properties comparable to covalent linear polymers (Figure
1).36,37 Here, we dramatically expand the modularity of this
design by including the pyridine heterocycle and hydrophobic
solubilizing groups in a single monomer, thereby enabling the
efficient incorporation of many dialdehydes into macrocycles
that assemble into high-aspect ratio nanotubes under mild
conditions (Figure 1). Through this approach, ten distinct
macrocycles and nanotubes with a range of structural features
including different shapes, channel sizes, and chemical
functionalities were realized. Because each of these macrocycles
forms nanotubes in the presence of less than one equivalent of
acid per pyridine moiety, we hypothesized that protons might be
INTRODUCTION
■
Macrocycles that assemble into extended one-dimensional
nanotubes exhibit emergent properties because of their low
dimensionality, structural regularity, and distinct interior
environments.1−10 These features are of potential interest for
ion transport,11−13 sensing,14−16 catalysis,17,18 and separa-
tions.19,20 To access the diverse properties associated with
these potential uses, macrocycles that form nanotubes must be
derived from readily accessible building blocks and tolerate
structural variation without compromising their interaction
energies and ability to assemble. General methods to access
designed, high-aspect ratio nanotubes remain limited. Non-
covalent assemblies based on relatively weak supramolecular
interactions are less likely to tolerate significant structural
variation and can exhibit poor mechanical integrity.6,21−26
Developing a robust and chemically general macrocycle
assembly strategy will enable broad explorations into nanotube
design, their emergent properties, and stimuli-responsive27−30
or even out-of-equilibrium assembly processes.31−34
Received: March 15, 2021
Published: May 18, 2021
We recently found that the protonation of imine-linked
macrocycles triggers strong electrostatic and solvophobic
interactions that drive the formation of high-aspect ratio
nanotubes.35−37 However, macrocycle assembly that relied
exclusively on imine protonation only assembled in the presence
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Figure 1. Accessing high-aspect ratio nanotubes via acid-mediated macrocycle assembly. (Top) Previous work in which assembly under mild
conditions was dictated by a pyridine-2,6-dicarboxaldehyde monomer residue, resulting in a system that assembles under mild conditions but is not
easily generalized. (Bottom) A modular approach to imine-linked macrocycle formation and assembly relying on a pyridine junction embedded within
the diamine monomer, allowing access to chemically and structurally diverse nanotubes in a single step.
mobile within the nanotube interiors, similar to recent reports
on proton conduction within assembled D,L-α-cyclic pep-
tides38,39 and nanotubes based on metal−ligand coordination
bonds.40 Electrochemical impedance spectroscopy of four
nanotube structures indicated that each system exhibited
measurable protonic conductivity, with the highest value of
1.6 × 10−3 S m−1 at 90% relative humidity and 25 °C. Across the
four nanotubes studied, the protonic conductivities appear to
depend on the size and/or shape of the macrocycle. These
findings highlight the potential of well-defined supramolecular
assemblies with precisely installed functional groups for ion
transport. Overall, this versatile synthetic platform to target
designed nanotubes will enable the broad exploration of
synthetic 1D nanostructures, their emergent properties, and
their eventual incorporation into devices.
functionality, 5-bromoisophthalaldehyde (5-Br-IDA) and 5-
ethynylisophthalaldehyde (5-E-IDA), and internal functional-
ity, 2-bromoisophthalaldehyde (2-Br-IDA; Schemes S14−S18).
These functional groups offer many possibilities for post-
synthetic transformations, such as cross-coupling reactions or
dipolar cycloadditions, further contributing to the structural
diversity available to these systems.41−45 Unlike previous
reports, in which linear dialdehydes yielded [6 + 6] macrocycles
when condensed with a 1,3,5-triphenylbenzene-based dia-
mine,35,46 the condensation of linear dialdehydes with DAPP
yielded pentagonal [5 + 5] systems. We attribute this change in
macrocycle structure to the shorter C−N bonds (1.36 Å) that
make up the pyridine core of DAPP, relative to the C−C bonds
(1.40 Å) within the benzene ring of the previously studied
system.47,48 The shorter C−N bonds result in a decreased bite
angle between the two reactive amines from 120° to 108°,
favoring the formation of a pentagonal structure. This approach
yielded structurally and electronically diverse macrocycles using
terephthalaldehyde (PDA), 2,3,5,6-tetrafluoroterephthalalde-
hyde (F4−PDA),49,50 2,5-dimethoxyterephthalaldehyde
(DiOMe-PDA),51,52 and 9,10-anthracenedicarboxaldehyde
(9,10-ADA) monomers (Schemes S19−22).53,54 Lastly, we
prepared a diamond shaped [2 + 2] macrocycle from DAPP and
4,4′-(1,10-phenanthroline-2,9-diyl)dibenzaldehyde (PhenDA)
which can chelate metals within the phenanthroline binding
pocket (Scheme S23)55,56 The ability to target macrocycles of
different sizes, chemical functionalities, and intrinsic properties
highlights the modularity of this approach, and its overall utility
in constructing precisely functionalized nanostructures.
RESULTS AND DISCUSSION
■
We prepared ten structurally diverse imine-linked macrocycles
in high isolated yields (>90%) by condensing various aromatic
dialdehydes with a 2,4,6-triphenylpyridine-based diamine
(DAPP) in the presence of trifluoroacetic acid (0.5 equiv per
DAPP). Trifluoroacetic acid was chosen because it is a strong
acid without substantial water content, whose ammonium salts
often remain soluble in organic solvents (Figure 2A); 0.5 equiv
of CF3CO2H per pyridine ring is sufficient to induce macrocycle
assembly while ensuring that no free CF3CO2H is present in
solution. meta-Substituted dialdehydes yielded hexagonal
macrocycles containing three diamine monomer residues and
three dialdehyde monomer residues (i.e., [3 + 3] systems).
Using this approach, macrocycles based on isophthalaldehyde
(IDA) and pyridine-2,6-dicarboxaldehyde (DFP) were synthe-
sized, similar to those in previous reports.37 This modular
approach allowed access to macrocycles with externally facing
Characterization of the monomeric macrocycles by gel
permeation chromatography (GPC), matrix-assisted laser
desorption ionization mass spectrometry (MALDI-MS), and
1H NMR spectroscopy confirmed their structures as the
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Figure 2. Modular synthesis of imine-linked macrocycles from a pyridine-containing diamine monomer. (A) Scheme of macrocycle synthesis where
the shape and size of the macrocycle is dictated by the dialdehyde substitution pattern. (B) GPC traces using a 254 nm ultraviolet (UV) detector. The
color of the chromatogram correlates to the color of the dialdehyde monomer. (C) MALDI-MS spectra of the synthesized macrocycles. The color of
the spectrum correlates to the color of the dialdehyde monomer.
proposed [5 + 5], [3 + 3], and [2 + 2] systems. All of these
macrocycles yielded a single, narrow elution band (Đ < 1.05) in
their GPC traces, consistent with the formation of a single
macrocyclic product (Figure 2B). MALDI-MS of each macro-
cycle showed a single set of peaks corresponding to the expected
[5 + 5], [3 + 3], or [2 + 2] macrocycle, with the [M + H]+ adduct
being within 0.04% of the theoretical molecular weight (Figure
2C and Table S1). Each macrocycle was soluble in common
measurements. Unassembled macrocycles do not produce
observable diffraction.36 However, when macrocycles assemble
into nanotubes, the emergence of a strong diffraction signal, with
a characteristic peak at low values of q related to the macrocycle
size (between 0.1 and 0.2 Å−1)35−37 is observed. Macrocycle
assembly was observed following condensation of DAPP with all
dialdehydes studied, thereby demonstrating that pyridine-based
assembly without requiring excess acid is general (Figure 3A,B).
The <100> diffraction features of the [3 + 3] systems,
corresponding to the size of the hexagonal pore, were observed
at 0.15 to 0.17 Å−1, which is consistent with our previous report
on similar hexagonal systems.37 Due to the increased size of the
[5 + 5] macrocycles, their <100> diffraction feature shifted to
lower values of q (0.12 to 0.13 Å−1). Despite having a pentagonal
shape, which is classically not able to pack into a periodic array,57
a diffraction pattern similar to that of the hexagonal systems was
observed, which we attribute to the ability of the flexible alkyloxy
side chains to fill free volume. Lastly, the primary diffraction
feature for the [2 + 2] PhenDA macrocycle assembly was
observed at 0.15 Å−1. Despite being comprised of fewer
monomers, the shape of PhenDA results in an assembly with
an irregularly shaped pore that is similar in size to the hexagonal
[3 + 3] systems. In all cases, the experimentally obtained XRD
1
organic solvents and exhibited H NMR spectra consisting of
well-defined resonances with integrations commensurate with
the proposed structures (see Supporting Information), along
with the absence of resonances corresponding to either free
aldehydes or free amines. The narrow GPC traces, 1H NMR and
MALDI-MS spectra, and high isolated yields (>90%) of each
macrocycle are indicative of a highly efficient and general
macrocyclization process which we have previously shown to be
driven by an out-of-equilibrium crystallization process that
drastically reduces imine-reactivity.37,46
The use of a pyridine-containing diamine yielded universal
access to crystalline nanotubes in a single step, as evaluated by in
solvo synchrotron X-ray diffraction (XRD). After the macro-
cyclization reaction was allowed to run for 24 h, the resultant gel
was placed in a capillary tube and subjected to XRD
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Figure 3. Assembly of imine-linked macrocycles into nanotubes during macrocycle synthesis (0.5 equiv CF3CO2H per DAPP). (A) Schematic of
nanostructures resulting from the assembly of pentagonal [5 + 5], hexagonal [3 + 3], and diamond shaped [2 + 2] macrocycles. (B) XRD patterns of
the synthesized nanotubes accompanied by the structure of the aldehyde monomer. In all cases, the dashed line represents the location of the imine
linkage. (C) AFM images of nanotubes with varying dimensions and functionalities. The color of the border correlates to the color of the aldehyde
monomer. Scale bars: 7 μm.
patterns are in good agreement with a Pawley refined pattern
corresponding to macrocycle assembly (see Supporting
Information). Overall, the emergence of diffraction signals
during the macrocycle synthesis confirms our hypothesis that
condensing a pyridine-based diamine with various aromatic
dialdehydes enables chemically general tandem macrocycliza-
tion and 1D assembly events.
Atomic force microscopy (AFM) and scanning electron
microscopy (SEM) confirmed that macrocycles prepared from
DAPP and various aromatic dialdehydes assembled into high-
aspect ratio nanotubes during their synthesis. While the
emergence of XRD signals demonstrated macrocycle assembly,
these microscopy techniques showed that nanotubes are formed
as mesoscale assemblies. Aliquots of all macrocyclizations were
drop-cast onto silicon wafers and imaged first by AFM, then by
SEM (see Supporting Information). In all cases, high-aspect
ratio nanotube formation was observed (Figure 3C).36,37 We
showed in previous reports that the absence of a central pyridine
ring prevents long-range assembly under analogous conditions,
which suggests that protonation to pyridinium ions drives
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organization through charge-mediated assembly.37,46 These data
highlight the modularity of this approach, in that, nanotubes
with high-aspect ratios were prepared in a single-step despite the
constituent macrocycles having different sizes, shapes, and
chemical functionalities.
Accessing nanotubes of different sizes and chemical
functionalities under sub-stoichiometric acid loadings motivated
studies of their proton conductivity. Nanotubes assembled from
pyridine-containing imine-linked macrocycles in the presence of
0.5 equiv CF3CO2H per pyridine group demonstrated pore size-
dependent proton conductivity, with nanotubes assembled from
DAPP-IDA exhibiting a conductivity 2 orders of magnitude
greater than that of nanotubes assembled from DAPP-PDA or
DAPP-PhenDA. To measure the proton conductivity, nano-
tubes were drop-cast onto a two-terminal device, between two
Au contacts (2.5 × 2.0 cm) separated by 50 μm, and subjected to
electrochemical impedance spectroscopy (EIS) at 90% relative
humidity (R.H., Figure 4A). EIS data was analyzed using
Nyquist plots fit to a standard equivalent circuit consisting of a
constant phase element (CPEint) in series with a parallel
combination of a resistor (Rb) and a capacitor (Cb, Figure 4B).
Despite variation in nanotube shape and number of pyridine
moieties, nanotubes assembled from DAPP-PDA, DAPP-IDA,
and DAPP-PhenDA all yield a semicircle Nyquist plot in the
high-frequency region and an inclined spur in the low frequency
region (Figure 4C−F). These observations are fingerprints of
proton conductivity, a phenomenon which was further validated
by observing a sharp decrease in conductivity due to isotope
effects when the same measurements were carried out in the
presence of D2O (Figure S134).58−60 The measured deuterium
effect is as expected for protons being the major charge carrier
within the nanotubes and rules out the possibility that other
ions, such as ions present in the solvent or the acid counterion,
contribute substantially to the measured current. All samples
demonstrate the hallmarks of proton conductivity, and our
observations suggest that the conductivity values of various
nanotubes have a pore size dependence. Larger [5 + 5]
nanotubes (Ø = 3 nm) derived from PDA exhibited low
Figure 4. Structure-dependent proton conductivity of nanotubes
prepared via acid-mediated macrocycle assembly. (A) Illustration of the
two-terminal device used for EIS measurements. (B) Diagram of the
equivalent circuit model used to analyze the impedance data. The
circuit consists of a Constant Phase Element (CPEint) in series with
both a resistor (Rb) and a capacitor (Cb), which correspond to the film/
electrode interface capacitance, the film bulk resistance, and the film
bulk capacitance, respectively. (C−F) Nyquist plots showing the
impedance of nanotubes derived from DAPP-PDA, DAPP-PhenDA,
DAPP-IDA, and DAPB-DFP macrocycles at 25 °C with 90% R.H. The
conductivities calculated from these plots were 1.4 × 10−5, 6.3 × 10−5,
1.6 × 10−3, and 1.5 × 10−3 S m−1, respectively. (G) Comparison of
observed conductivity values in different macrocycles. The data suggest
that an increase in the size of the macrocycle results in lower
conductivities, but other factors such as macrocycle shape and packing
density may also play a role.
conductivity (1.4
0.0 × 10−5 S m−1, 90% R.H., 25 °C).
However, the smaller but irregularly shaped nanotubes (Ø = 2.5
and 1.3 nm) derived from PhenDA only showed a moderate
conductivity increase (6.3 0.2 × 10−5 S m−1, 90% R.H., 25 °C).
The smallest hexagonal nanotubes (Ø = 1.75 nm) derived from
IDA produced a conductivity 2 orders of magnitude greater than
nanotubes with larger channels (1.6 0.0 × 10−3 S m−1, 90%
R.H., 25 °C), suggesting that the size of the hexagonal pore and
the spacing of pyridine moieties in nanotubes derived from IDA
provide an optimal path for proton conduction. Pore size-
dependent proton conductivity within 1D nanochannels has
been previously attributed to water molecules adopting a well-
organized 1D proton wire configuration in smaller systems,
thereby realizing larger conductivity values.61,62 Despite the
apparent dependence of proton conductivity on nanotube
diameter, further studies will be needed to definitively elucidate
the origin of enhanced conductivity within various nanotubes
and to investigate structure−property relationships that
promote proton conductivity within these macrocycle-based
assemblies. Furthermore, it is likely that the proton conductivity
of the nanotubes can be enhanced by increasing the amount of
acid used in their assembly, offering a handle to tune
conductivity that is independent of macrocycle structure.63
Comparison of the conductivity trends in nanotubes derived
from DAPP with two additional control systems confirmed that
proton transport occurs along the cationic 1D nanochannel.
Two additional macrocycles were prepared based on a 1,3,5-
triphenylbenzene-based diamine (DAPB) and either DFP or
IDA.36,37 The former is a structural isomer of DAPP-IDA with
an identical assembly profile, while the latter lacks pyridine
moieties and substantial 1D order, allowing us to further probe
the effects of assembly and nanotube size on proton
conductivity. Nanotubes assembled from DAPB-DFP macro-
cycles exhibit proton conductivities (1.5 0.0 × 10−3 S m−1,
90% R.H., 25 °C), similar to DAPP-IDA systems. Furthermore,
macrocycles which do not contain any pyridine moieties, and
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therefore lack substantial 1D order (DAPB-IDA), demonstrate
conductivity values at least 3 orders of magnitude lower than
those of DAPP-IDA or DAPB-DFP nanotubes (Figure S135).
The comparison of these three hexagonal structures suggests
that (1) proton conductivity is partially dependent on the pore
architecture and (2) substantial 1D order is required for reliable
proton transport. Taken together, the results of the conductivity
values obtained for various DAPP-based nanotubes highlight
that in order to reliably target optimized performance in a 1D
nanochannel, the chemical functionality and nanotube topology
must be independently modifiable. Presumably, using this
design strategy to prepare optimally sized nanotubes with higher
densities of basic moieties will improve the proton conductivity
of these assemblies, thereby enabling explorations into the use of
these materials in fuel cell and bioelectronic applications.64
More broadly, this work demonstrates that structurally well-
defined supramolecular assemblies with precisely installed
chemical functionalities are promising scaffolds for the develop-
ment of materials suitable for ion transport.
States; orcid.org/0000-0001-7898-2479;
Email: mrolandi@ucsc.edu
William R. Dichtel − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States;
orcid.org/0000-0002-3635-6119; Email: wdichtel@
northwestern.edu
Authors
Michael J. Strauss − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States;
orcid.org/0000-0003-0808-2568
Manping Jia − Department of Electrical and Computer
Engineering, Baskin School of Engineering, University of
California Santa Cruz, Santa Cruz, California 95064, United
States
Austin M. Evans − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States;
orcid.org/0000-0002-3597-2454
Ioannina Castano − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States;
orcid.org/0000-0001-6491-2170
Rebecca L. Li − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States;
orcid.org/0000-0001-7208-3413
Xavier Aguilar-Enriquez − Department of Chemistry,
Northwestern University, Evanston, Illinois 60208, United
States; orcid.org/0000-0002-5940-4427
Emily K. Roesner − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States;
orcid.org/0000-0003-0583-7371
Jeremy L. Swartz − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States
Anton D. Chavez − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States;
Department of Chemistry and Chemical Biology, Cornell
University, Ithaca, New York 14853, United States
Alan E. Enciso − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States
J. Fraser Stoddart − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States; School of
Chemistry, University of New South Wales, Sydney, NSW
2052, Australia; Stoddart Institute of Molecular Science,
Department of Chemistry, Zhejiang University, Hangzhou
310027, China; ZJU-Hangzhou Global Scientific and
Technological Innovation Center, Hangzhou 311215, China;
orcid.org/0000-0003-3161-3697
CONCLUSIONS
■
Generalizing the acid-mediated assembly of macrocycles into
robust nanotubes will enable access to a broad range of
structures and exploration of their emergent properties. Here,
we have shown that a 2,4,6-triphenylpyridine-based diamine
(DAPP) enables efficient formation of pentagonal [5 + 5],
hexagonal [3 + 3], and diamond shaped [2 + 2] macrocycles
depending on the substitution pattern of the aromatic
dialdehyde monomer. Protonation of the central pyridine
moiety of DAPP under the mild conditions typical for
macrocycle synthesis drives macrocycle assembly into high-
aspect ratio nanotubes, as demonstrated by in solvo XRD
measurements and AFM imaging. These structurally well-
defined supramolecular polymers with cationic 1D nano-
channels demonstrated pore size-dependent proton conductiv-
ity, with nanotubes derived from IDA exhibiting a conductivity 2
orders of magnitude greater than those of the nanotubes derived
from PDA or PhenDA. These findings, along with the versatility
of this synthetic approach, will guide future designs to further
improve proton conductivity and further leverage the stimuli-
responsive nature of the assemblies. Overall, this platform will
unlock the potential of functional nanotubes assembled from
macrocyclic precursors to provide systems whose emergent
properties and functions can be rationally tuned through
molecular design.
Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.1c02789
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.1c02789.
Notes
The authors declare no competing financial interest.
Instrumentation, synthetic and experimental procedures,
NMR spectra, FTIR spectra, GPC chromatograms,
MALDI-MS spectra, in solvo XRD patterns, Pawley
structural refinements, SEM images, AFM images, EIS
methods and data (PDF)
ACKNOWLEDGMENTS
■
This work was funded by the Army Research Office through the
Multidisciplinary University Research Initiative (MURI;
W911NF-15-1-04477, to W.R.D.). M.J.S was supported by the
National Science Foundation (NSF) through the Graduate
Research Fellowship Program (GRFP) under Grant No. DGE-
1842165. M.J.S. is partially supported by the Ryan Fellowship
and the International Institute for Nanotechnology. A.M.E. was
supported by the NSF through the GRFP under Grant No.
DGE-1324585. I.C. was supported by the NSF through the
GRFP under Grant No. DGE-1842165. X.A.E. was supported by
AUTHOR INFORMATION
■
Corresponding Authors
Marco Rolandi − Department of Electrical and Computer
Engineering, Baskin School of Engineering, University of
California Santa Cruz, Santa Cruz, California 95064, United
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́
(4) Step̧ ien, M.; Donnio, B.; Sessler, J. L. Supramolecular Liquid
the NSF through the GRFP under Grant No. DGE-1842165.
J.L.S. was supported by the NSF through the GRFP under Grant
No. DGE-1842165. This work made use of the Integrated
Molecular Structure Education and Research Center (IM-
SERC) at Northwestern University, which has received support
from the NSF (CHE-1048773), the Soft and Hybrid Nano-
technology Experimental (SHyNE) Resource (NSF; NNCI-
1542205), the State of Illinois, and the International Institute for
Nanotechnology (IIN). This work also made use of the Scanned
Probe Imaging and Development (SPID), and the Electron
Probe Instrumentation Center (EPIC), facilities of Northwest-
ern University’s Atomic and Nanoscale Characterization
Experiment Center (NUANCE), which has received support
from the Soft and Hybrid Nanotechnology Experimental
(SHyNE) Resource (NSF; ECCS-1542205); the MRSEC
program (NSF; DMR-1720139) at the Materials Research
Center; the International Institute for Nanotechnology (IIN);
the Keck Foundation; and the State of Illinois. Instruments used
in this work were also supported by the Northwestern University
Keck Biophysics Facility and a Cancer Center Support Grant
(NCI CA060553). Parts of this work were performed at the
DuPont-Northwestern-Dow Collaborative Access Team
(DND-CAT) located at Sector 5 of the Advanced Photon
Source (APS) at Argonne National Lab. This research used
resources of the Advanced Photon Source and the Center for
Nanoscale Materials, both U.S. Department of Energy (DOE)
Office of Science User Facilities operated for the DOE Office of
Science by Argonne National Laboratory under Grant No.
DGE-1324585. M.J. and M.R. thank the W.M. Keck Center for
Nanoscale Optofluidics, the California Institute for Quantitative
Biosciences (QB3), and the Army Research Office under award
number W911NF-17-1-0460 for equipment and facilities
support, and funding from the Defense Advanced Research
Projects Agency (DARPA) and the Department of Interior
under award No. D20AC00003. We acknowledge Prof. Julia
Kalow for the use of her GPC instrument. We also acknowledge
Prof. Christine Luscombe for helpful discussions.
Crystals Based on Cyclo[8]pyrrole. Angew. Chem., Int. Ed. 2007, 46,
1431−1435.
(5) Zhang, J.; Moore, J. S. Nanoarchitectures. Liquid Crystals Based
on Shape-Persistent Macrocyclic Mesogens. J. Am. Chem. Soc. 1994,
116, 2655−2656.
(6) Shimizu, T.; Ding, W.; Kameta, N. Soft-Matter Nanotubes: A
Platform for Diverse Functions and Applications. Chem. Rev. 2020, 120,
2347−2407.
(7) Li, J.; Cvrtila, I.; Colomb-Delsuc, M.; Otten, E.; Otto, S. An
“Ingredients” Approach to Functional Self-Synthesizing Materials: A
Metal-Ion-Selective, Multi-Responsive, Self-Assembled Hydrogel.
Chem. - Eur. J. 2014, 20, 15709−15714.
(8) Kline, M. A.; Wei, X.; Horner, I. J.; Liu, R.; Chen, S.; Chen, S.;
Yung, K. Y.; Yamato, K.; Cai, Z.; Bright, F. V.; Zeng, X. C.; Gong, B.
Extremely strong tubular stacking of aromatic oligoamide macrocycles.
Chem. Sci. 2015, 6, 152−157.
(9) Wu, X.; Liu, R.; Sathyamoorthy, B.; Yamato, K.; Liang, G.; Shen,
L.; Ma, S.; Sukumaran, D. K.; Szyperski, T.; Fang, W.; He, L.; Chen, X.;
Gong, B. Discrete Stacking of Aromatic Oligoamide Macrocycles. J. Am.
Chem. Soc. 2015, 137, 5879−5882.
(10) Kinney, Z. J.; Kirinda, V. C.; Hartley, C. S. Macrocycles of higher
ortho-phenylenes: assembly and folding. Chem. Sci. 2019, 10, 9057−
9068.
(11) Helsel, A. J.; Brown, A. L.; Yamato, K.; Feng, W.; Yuan, L.;
Clements, A. J.; Harding, S. V.; Szabo, G.; Shao, Z.; Gong, B. Highly
Conducting Transmembrane Pores Formed by Aromatic Oligoamide
Macrocycles. J. Am. Chem. Soc. 2008, 130, 15784−15785.
(12) Xu, H.; Nagasaka, S.; Kameta, N.; Masuda, M.; Ito, T.; Higgins,
D. A. Imaging fluorescence correlation spectroscopy studies of dye
diffusion in self-assembled organic nanotubes. Phys. Chem. Chem. Phys.
2016, 18, 16766−16774.
(13) Xu, H.; Nagasaka, S.; Kameta, N.; Masuda, M.; Ito, T.; Higgins,
D. A. Spectroscopic imaging studies of nanoscale polarity and mass
transport phenomena in self-assembled organic nanotubes. Phys. Chem.
Chem. Phys. 2017, 19, 20040−20048.
(14) de la Rica, R.; Mendoza, E.; Matsui, H. Bioinspired Target-
Specific Crystallization on Peptide Nanotubes for Ultrasensitive Pb Ion
Detection. Small 2010, 6, 1753−1756.
(15) Kameta, N.; Masuda, M.; Shimizu, T. Two-step naked-eye
detection of lectin by hierarchical organization of soft nanotubes into
liquid crystal and gel phases. Chem. Commun. 2015, 51, 6816−6819.
(16) Hu, Y.; Ma, X.; Zhang, Y.; Che, Y.; Zhao, J. Detection of Amines
with Fluorescent Nanotubes: Applications in the Assessment of Meat
Spoilage. ACS Sensors 2016, 1, 22−25.
(17) Yang, J.; Dewal, M. B.; Shimizu, L. S. Self-Assembling Bisurea
Macrocycles Used as an Organic Zeolite for a Highly Stereoselective
Photodimerization of 2-Cyclohexenone. J. Am. Chem. Soc. 2006, 128,
8122−8123.
(18) Xu, Y.; Wang, T.; He, Z.; Zhong, A.; Yu, W.; Shi, B.; Huang, K.
Synthesis of triphenylphosphine-based microporous organic nanotube
framework supported Pd catalysts with excellent catalytic activity.
Polym. Chem. 2016, 7, 7408−7415.
(19) Kameta, N.; Dong, J.; Yui, H. Thermoresponsive PEG-Coated
Nanotubes as Chiral Selectors of Amino Acids and Peptides. Small
2018, 14, 1800030.
(20) Kameta, N.; Ding, W.; Dong, J. Soft Nanotubes Derivatized with
Short PEG Chains for Thermally Controllable Extraction and
Separation of Peptides. ACS Omega 2017, 2, 6143−6150.
(21) Leonhardt, E. J.; Van Raden, J. M.; Miller, D.; Zakharov, L. N.;
Alemán, B.; Jasti, R. A Bottom-Up Approach to Solution-Processed,
Atomically Precise Graphitic Cylinders on Graphite. Nano Lett. 2018,
18, 7991−7997.
ABBREVIATIONS
■
DAPP, 4-(4-decyloxyphenyl)-2,6-bis(4-aminophenyl)pyridine;
DAPB, 1-(4-decyloxyphenyl)-3,5-bis(4-aminophenyl)benzene;
PDA, terephthalaldehyde, DiOMe-PDA, 2,5-dimethoxytereph-
thalaldehyde; F4−PDA, 2,3,5,6-tetrafluoroterephthalaldehyde;
9,10-ADA, 9,10-anthracenedicarboxaldehyde; DFP, pyridine-
2,6-dicarboxaldehyde; IDA, isophthalaldehyde; 5-Br-IDA, 5-
bromoisophthaldehyde; 2-Br-IDA, 2-bromoisophthalaldehyde;
5-E-IDA, 5-ethynylisophthalaldehyde; PhenDA, 4,4′-(1,10-
phenanthroline-2,9-diyl)dibenzaldehyde; GPC, gel permeation
chromatography; MALDI-MS, matrix-assisted laser desorption
ionization mass spectrometry; R.H., relative humidity; EIS,
electrochemical impedance spectroscopy.
REFERENCES
■
(1) Iijima, S. Helical microtubules of graphitic carbon. Nature 1991,
354, 56−58.
(2) Sato, K.; Itoh, Y.; Aida, T. Columnarly Assembled Liquid-
Crystalline Peptidic Macrocycles Unidirectionally Orientable over a
Large Area by an Electric Field. J. Am. Chem. Soc. 2011, 133, 13767−
13769.
(3) Fischer, M.; Lieser, G.; Rapp, A.; Schnell, I.; Mamdouh, W.; De
Feyter, S.; De Schryver, F. C.; Höger, S. Shape-Persistent Macrocycles
with Intraannular Polar Groups: Synthesis, Liquid Crystallinity, and 2D
Organization. J. Am. Chem. Soc. 2004, 126, 214−222.
(22) Ghadiri, M. R.; Granja, J. R.; Milligan, R. A.; McRee, D. E.;
Khazanovich, N. Self-assembling organic nanotubes based on a cyclic
peptide architecture. Nature 1993, 366, 324−327.
(23) Lahiri, S.; Thompson, J. L.; Moore, J. S. Solvophobically Driven
π-Stacking of Phenylene Ethynylene Macrocycles and Oligomers. J. Am.
Chem. Soc. 2000, 122, 11315−11319.
8151
https://doi.org/10.1021/jacs.1c02789
J. Am. Chem. Soc. 2021, 143, 8145−8153

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
(24) Shimizu, L. S.; Hughes, A. D.; Smith, M. D.; Davis, M. J.; Zhang,
B. P.; zur Loye, H.-C.; Shimizu, K. D. Self-Assembled Nanotubes that
Reversibly Bind Acetic Acid Guests. J. Am. Chem. Soc. 2003, 125,
14972−14973.
(43) Lowe, A. B. Thiol-yne ‘click’/coupling chemistry and recent
applications in polymer and materials synthesis and modification.
Polymer 2014, 55, 5517−5549.
(44) Lowe, A. B.; Hoyle, C. E.; Bowman, C. N. Thiol-yne click
chemistry: A powerful and versatile methodology for materials
synthesis. J. Mater. Chem. 2010, 20, 4745−4750.
(25) Gallant, A. J.; MacLachlan, M. J. Ion-Induced Tubular Assembly
of Conjugated Schiff-Base Macrocycles. Angew. Chem., Int. Ed. 2003,
42, 5307−5310.
(45) Wang, Y.; Zhang, S.; Wang, L.; Zhang, W.; Zhou, N.; Zhang, Z.;
Zhu, X. The Suzuki coupling reaction as a post-polymerization
modification: a promising protocol for construction of cyclic-brush
and more complex polymers. Polym. Chem. 2015, 6, 4669−4677.
(46) Chavez, A. D.; Evans, A. M.; Flanders, N. C.; Bisbey, R. P.;
Vitaku, E.; Chen, L. X.; Dichtel, W. R. Equilibration of Imine-Linked
Polymers to Hexagonal Macrocycles Driven by Self-Assembly. Chem. -
Eur. J. 2018, 24, 3989−3993.
(26) Rubin, D. J.; Amini, S.; Zhou, F.; Su, H.; Miserez, A.; Joshi, N. S.
Structural, Nanomechanical, and Computational Characterization of
D,L-Cyclic Peptide Assemblies. ACS Nano 2015, 9, 3360−3368.
(27) Balkenende, D. W. R.; Monnier, C. A.; Fiore, G. L.; Weder, C.
Optically responsive supramolecular polymer glasses. Nat. Commun.
2016, 7, 10995.
(28) Albertazzi, L.; van der Veeken, N.; Baker, M. B.; Palmans, A. R.
A.; Meijer, E. W. Supramolecular copolymers with stimuli-responsive
sequence control. Chem. Commun. 2015, 51, 16166−16168.
(29) Webber, M. J. Engineering responsive supramolecular bio-
materials: Toward smart therapeutics. Bioeng. Transl. Med. 2016, 1,
252−266.
(30) Kumar, M.; Brocorens, P.; Tonnelé, C.; Beljonne, D.; Surin, M.;
George, S. J. A dynamic supramolecular polymer with stimuli-
responsive handedness for in situ probing of enzymatic ATP hydrolysis.
Nat. Commun. 2014, 5, 5793.
(31) Wanzke, C.; Jussupow, A.; Kohler, F.; Dietz, H.; Kaila, V. R. I.;
Boekhoven, J. Dynamic Vesicles Formed By Dissipative Self-Assembly.
ChemSystemsChem 2020, 2, e1900044.
(47) Schiavo, E.; Munoz-García, A. B.; Barone, V.; Vittadini, A.;
̃
Casarin, M.; Forrer, D.; Pavone, M. Tuning dispersion correction in
DFT-D2 for metal-molecule interactions: A tailored reparameterization
strategy for the adsorption of aromatic systems on Ag(1 1 1). Chem.
Phys. Lett. 2018, 693, 28−33.
(48) Cumper, C. W. N. The structures of some heterocyclic
molecules. Trans. Faraday Soc. 1958, 54, 1266−1270.
(49) Weck, M.; Dunn, A. R.; Matsumoto, K.; Coates, G. W.;
Lobkovsky, E. B.; Grubbs, R. H. Influence of Perfluoroarene−Arene
Interactions on the Phase Behavior of Liquid Crystalline and Polymeric
Materials. Angew. Chem., Int. Ed. 1999, 38, 2741−2745.
(50) Elacqua, E.; Geberth, G. T.; Vanden Bout, D. A.; Weck, M.
Synthesis and folding behaviour of poly(p-phenylene vinylene)-based
β-sheet polychromophores. Chem. Sci. 2019, 10, 2144−2152.
(51) Wang, S.; Chavez, A. D.; Thomas, S.; Li, H.; Flanders, N. C.; Sun,
C.; Strauss, M. J.; Chen, L. X.; Markvoort, A. J.; Brédas, J.-L.; Dichtel,
W. R. Pathway Complexity in the Stacking of Imine-Linked
Macrocycles Related to Two-Dimensional Covalent Organic Frame-
works. Chem. Mater. 2019, 31, 7104−7111.
(32) Dai, K.; Fores, J. R.; Wanzke, C.; Winkeljann, B.; Bergmann, A.
M.; Lieleg, O.; Boekhoven, J. Regulating Chemically Fueled Peptide
Assemblies by Molecular Design. J. Am. Chem. Soc. 2020, 142, 14142−
14149.
(33) Kriebisch, B. A. K.; Jussupow, A.; Bergmann, A. M.; Kohler, F.;
Dietz, H.; Kaila, V. R. I.; Boekhoven, J. Reciprocal Coupling in
Chemically Fueled Assembly: A Reaction Cycle Regulates Self-
Assembly and Vice Versa. J. Am. Chem. Soc. 2020, 142, 20837−20844.
(34) van Rossum, S. A. P.; Tena-Solsona, M.; van Esch, J. H.; Eelkema,
R.; Boekhoven, J. Dissipative out-of-equilibrium assembly of man-made
supramolecular materials. Chem. Soc. Rev. 2017, 46, 5519−5535.
(35) Sun, C.; Shen, M.; Chavez, A. D.; Evans, A. M.; Liu, X.;
Harutyunyan, B.; Flanders, N. C.; Hersam, M. C.; Bedzyk, M. J.; Olvera
de la Cruz, M.; Dichtel, W. R. High aspect ratio nanotubes assembled
from macrocyclic iminium salts. Proc. Natl. Acad. Sci. U. S. A. 2018, 115,
8883−8888.
(36) Strauss, M. J.; Asheghali, D.; Evans, A. M.; Li, R. L.; Chavez, A.
D.; Sun, C.; Becker, M. L.; Dichtel, W. R. Cooperative Self-Assembly of
Pyridine-2,6-Diimine-Linked Macrocycles into Mechanically Robust
Nanotubes. Angew. Chem., Int. Ed. 2019, 58, 14708−14714.
(37) Strauss, M. J.; Evans, A. M.; Castano, I.; Li, R. L.; Dichtel, W. R.
Supramolecular polymerization provides non-equilibrium product
distributions of imine-linked macrocycles. Chem. Sci. 2020, 11,
1957−1963.
(38) Silberbush, O.; Engel, M.; Sivron, I.; Roy, S.; Ashkenasy, N. Self-
Assembled Peptide Nanotube Films with High Proton Conductivity. J.
Phys. Chem. B 2019, 123, 9882−9888.
(39) Lerner Yardeni, J.; Amit, M.; Ashkenasy, G.; Ashkenasy, N.
Sequence dependent proton conduction in self-assembled peptide
nanostructures. Nanoscale 2016, 8, 2358−2366.
(40) Otake, K.-i.; Otsubo, K.; Komatsu, T.; Dekura, S.; Taylor, J. M.;
Ikeda, R.; Sugimoto, K.; Fujiwara, A.; Chou, C.-P.; Sakti, A. W.;
Nishimura, Y.; Nakai, H.; Kitagawa, H. Confined water-mediated high
proton conduction in hydrophobic channel of a synthetic nanotube.
Nat. Commun. 2020, 11, 843.
(52) Xu, H.; Gao, J.; Jiang, D. Stable, crystalline, porous, covalent
organic frameworks as a platform for chiral organocatalysts. Nat. Chem.
2015, 7, 905−912.
(53) Nagaoka, M.; Tsurumaki, E.; Nishiuchi, M.; Iwanaga, T.; Toyota,
S. Synthesis and Electronic Properties of Length-Defined 9,10-
Anthrylene−Butadiynylene Oligomers. J. Org. Chem. 2018, 83,
5784−5790.
(54) Haldar, S.; Chakraborty, D.; Roy, B.; Banappanavar, G.; Rinku,
K.; Mullangi, D.; Hazra, P.; Kabra, D.; Vaidhyanathan, R. Anthracene-
Resorcinol Derived Covalent Organic Framework as Flexible White
Light Emitter. J. Am. Chem. Soc. 2018, 140, 13367−13374.
(55) Meyer, M.; Albrecht-Gary, A.-M.; Dietrich-Buchecker, C. O.;
Sauvage, J.-P. π−π Stacking-Induced Cooperativity in Copper(I)
Complexes with Phenanthroline Ligands. Inorg. Chem. 1999, 38, 2279−
2287.
(56) Liu, Y.; Ma, Y.; Zhao, Y.; Sun, X.; Gándara, F.; Furukawa, H.; Liu,
Z.; Zhu, H.; Zhu, C.; Suenaga, K.; Oleynikov, P.; Alshammari, A. S.;
Zhang, X.; Terasaki, O.; Yaghi, O. M. Weaving of organic threads into a
crystalline covalent organic framework. Science 2016, 351, 365−369.
(57) Bowers, P. L.; Stephenson, K. A ‘Regular’ Pentagonal Tiling of
the Plane. Conformal. Geom. Dyn. 1997, 1, 58−68.
(58) Bureekaew, S.; Horike, S.; Higuchi, M.; Mizuno, M.; Kawamura,
T.; Tanaka, D.; Yanai, N.; Kitagawa, S. Materials for Sustainable Energy
2010, 232−237.
(59) Selberg, J.; Jia, M.; Rolandi, M. Proton conductivity of
glycosaminoglycans. PLoS One 2019, 14, e0202713.
(60) Phillips, M.; Wheeler, A.; Robinson, M. J.; Leppert, V.; Jia, M.;
Rolandi, M.; Hirst, L. S.; Amemiya, C. T. Structural Characteristics and
Proton Conductivity of the Gel Within the Electrosensory Organs of
Cartilaginous Fishes. 2021.01.04. bioRxiv., https://www.biorxiv.org/
content/10.1101/2021.01.04.425255v1.full. (accessed 2021-03-14).
(61) Miyake, T.; Rolandi, M. Grotthuss mechanisms: from proton
transport in proton wires to bioprotonic devices. J. Phys.: Condens.
Matter 2016, 28, 023001.
(41) Merí-Bofí, L.; Royuela, S.; Zamora, F.; Ruiz-González, M. L.;
̃ ̃
Segura, J. L.; Munoz-Olivas, R.; Mancheno, M. J. Thiol grafted imine-
based covalent organic frameworks for water remediation through
selective removal of Hg(ii). J. Mater. Chem. A 2017, 5, 17973−17981.
(42) Huang, N.; Krishna, R.; Jiang, D. Tailor-Made Pore Surface
Engineering in Covalent Organic Frameworks: Systematic Function-
alization for Performance Screening. J. Am. Chem. Soc. 2015, 137,
7079−7082.
8152
https://doi.org/10.1021/jacs.1c02789
J. Am. Chem. Soc. 2021, 143, 8145−8153

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
(62) Zhong, C.; Deng, Y.; Roudsari, A. F.; Kapetanovic, A.; Anantram,
M. P.; Rolandi, M. A polysaccharide bioprotonic field-effect transistor.
Nat. Commun. 2011, 2, 476.
(63) Chandra, S.; Kundu, T.; Kandambeth, S.; BabaRao, R.; Marathe,
Y.; Kunjir, S. M.; Banerjee, R. Phosphoric Acid Loaded Azo (−N=N−)
Based Covalent Organic Framework for Proton Conduction. J. Am.
Chem. Soc. 2014, 136, 6570−6573.
(64) Jia, M.; Rolandi, M. Soft and Ion-Conducting Materials in
Bioelectronics: From Conducting Polymers to Hydrogels. Adv.
Healthcare Mater. 2020, 9, 1901372.
8153
https://doi.org/10.1021/jacs.1c02789
J. Am. Chem. Soc. 2021, 143, 8145−8153