Tunable Adhesion from Stoichiometry-Controlled and Sequence-Defined Supramolecular Polymers Emerges Hierarchically from Cyanostar-Stabilized Anion-Anion Linkages

Article abstract of DOI:10.1021/jacs.9b12645

Sequence-controlled supramolecular polymers offer new design paradigms for generating stimuli-responsive macromolecules with enhanced functionalities. The dynamic character of supramolecular links present challenges to sequence definition in extended supr

Full text of DOI:10.1021/jacs.9b12645

Subscriber access provided by UNIV OF NEBRASKA - LINCOLN
Article
Tunable Adhesion from Stoichiometry-controlled and
Sequence-defined Supramolecular Polymers Emerges
Hierarchically from Cyanostar-stabilized Anion-anion Linkages
Wei Zhao, Joshua Tropp, Bo Qiao, Maren Pink, Jason D. Azoulay, and Amar H Flood
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 14 Jan 2020
Downloaded from pubs.acs.org on January 14, 2020
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 43
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
J. Am. Chem. Soc.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Tunable Adhesion from Stoichiometry-controlled and Sequence-
defined Supramolecular Polymers Emerges Hierarchically from
Cyanostar-stabilized Anion-anion Linkages
†
‡
†,§
†
‡
,†
Wei Zhao, Joshua Tropp, Bo Qiao, Maren Pink, Jason D. Azoulay, and Amar H. Flood*
†
Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, IN
47405, USA.
‡
School of Polymer Science and Engineering, The University of Southern Mississippi, 118
College Drive, Hattiesburg, MS 39406, USA.
aflood@indiana.edu
1
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 43
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Abstract
Sequence-controlled supramolecular polymers offer new design paradigms for generating stimuli-
responsive macromolecules with enhanced functionalities. The dynamic character of
supramolecular links present challenges to sequence definition in extended supramolecular
macromolecules, and design principles remain nascent. Here, we demonstrate the first example of
using stoichiometry-control to specify the monomer sequence in a linear supramolecular polymer
by synthesizing both a homopolymer and an alternating copolymer from the same glycol-
substituted cyanostar macrocycle and phenylene-linked diphosphate monomers. A 2:1
stoichiometry between macrocycle and diphosphate produces a supramolecular homopolymer of
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
general formula (A) comprised of repeating units of cyanostar-stabilized phosphate-phosphate
n
dimers. Using a 1:1 stoichiometry, an alternating (AB) structure is produced with half the
n
phosphate dimers now stabilized by the additional counter cations that emerge hierarchically after
forming the stronger cyanostar-stabilized phosphate dimers. These new polymer materials and
binding motifs are sufficient to bear normal and shear stress to promote significant and tunable
adhesive properties. The homopolymer (A) , consisting of cyanostar-stabilized anti-electrostatic
n
linkages, shows adhesion strength comparable to commercial superglue formulations based on
polycyanoacrylate but is thermally reversible. Unexpectedly, and despite including traditional
ionic linkages, the alternating copolymer (AB) shows weaker adhesion strength more similar to
n
commercial white glue based on poly(vinyl acetate). Thus, the adhesion properties can be tuned
over a wide range by simply controlling the stoichiometric ratio of monomers. This study offers
new insight into supramolecular polymers composed of custom-designed anion and receptor
monomers and demonstrates the utility of emerging functional materials based on anion-anion
interactions.
2
ACS Paragon Plus Environment

Page 3 of 43
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Introduction
Emerging technologies derived from responsive supramolecular polymers 1-2 benefit from
the creation of versatile macromolecules with synthetically engineered functionalities.3-4 Interest
in supramolecular polymers5-7 continues unabated owing to the unique properties conferred by
their noncovalent connectivities and dynamic structures,8-9 as well as their potential for
applications in biomedicine,10-11 optoelectronics,12-13 and adaptive materials.14-15 These
applications benefit from chemically unique and reconfigurable macromolecular linkages
combined with well-defined sequences of monomer units.6,16 Pioneering efforts to control the
sequences of supramolecular polymers have relied on monomers encoded with orthogonal
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
7
18
supramolecular linkages, e.g., hydrogen bonding, metal-ligand coordination, and host-guest
1
9
recognition. These include heterotopic monomers bearing end-groups with orthogonal linkage
chemistries,20-29 and use of two different homotopic monomers with complementary binding
partners at either end.30-33 The orthogonal monomers enable self-sorting to define supramolecular
polymer sequences.28,34 However, use of a single homotopic monomer to achieve sequence control
is unknown. This outcome appears to be a contradiction given that the identical end-groups do not
offer pre-programmed orthogonality. Here we report the discovery of a single homotopic dianion
monomer (Figure 1a) that combines with a macrocycle (Figure 1b) where orthogonal recognition
chemistries emerge hierarchically (Figure 1c) to enable control over monomer sequence in homo
(
Figure 1d) and alternating35-36 (Figure 1e) supramolecular polymers simply by changing reaction
stoichiometry.
3
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 43
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 1. Structures of (a) the homotopic diphosphate with a rigid phenylene linker, (b) the new
cyanostar macrocycle, OTgCS, and linkage chemistries of (c) cyanostar-stabilized phosphate-
phosphate dimer (A) and cation-stabilized phosphate-phosphate dimer (B). Representation of
stoichiometry-controlled supramolecular polymers: (d) homopolymer (A) shows strong adhesion
n
and (e) the alternating copolymer (AB) shows weak adhesion.
n
4
ACS Paragon Plus Environment

Page 5 of 43
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Previous studies have demonstrated that variation in the reaction stoichiometry of the
monomers can control various features of supramolecular polymers. These include the topology
by toggling between linear and crosslinked states,37-39 and net chirality.40-42 Use of the
stoichiometry to control the sequences in linear supramolecular polymers, however, remains
nascent. The role of stoichiometry is well established in small molecule chemistry. Different host-
guest complexes can be made by altering stoichiometry37-38 but this functionality has yet to be
leveraged for controlling sequences in supramolecular polymers. There are, in general, very few
reported examples of using stoichiometry control. Among them, the closest involves addition of 3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
+
39
mole% of Eu to a linear zinc-coordinated supramolecular polymer to drive crosslinking. In
4
3
pioneering work from Sessler, stoichiometry was evident when using cationic macrocycles,
called “Texas-sized” boxes, combined with terephthalate monoanions where changing monomer
ratio from 3:2 to 1:1 drove a transition from a small-molecule complex to a supramolecular
polymer. In this case, however, the sequence of the supramolecular polymer was not tunable.
These examples highlight the underdeveloped nature of this approach to control the sequence of
supramolecular polymers. To the best of our knowledge, stoichiometry has not been used to control
the sequence of monomers to form well-defined homo and alternating supramolecular polymers.
To construct supramolecular polymers, reliable noncovalent interactions with high affinity
3
and fidelity are essential. To date, many well-defined recognition chemistries have been
developed and exploited to synthesize supramolecular polymers. The majority of examples are
based upon metal-coordination,44 hydrogen bonding,45-46 π-π interactions47-48 and host-guest
interactions.49-50 Studies involving anion coordination as the driving force for supramolecular
polymerization, however, account for less than 1% of the 10,000+ reports. We51-52 and
others21,43,53-59 have recently been working toward filling this gap by exploring the novel
5
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 43
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
noncovalent chemical connectivities promoted by anion receptors and anionic monomers. We
leveraged the high-fidelity dimerization of phosphonate hydroxyanions inside cyanostar
macrocycles as the driving force necessary for the formation of well-defined supramolecular
polymers.52 The cyanostar-stabilized anion-anion dimer constitutes a 2:2 recognition motif.
Therein, two (2) hydroxyanions dimerize through anti-electrostatic hydrogen bonding60-66 inside a
π-stacked pair (2) of cyanostar macrocycles. Although the elementary recognition has been
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
– 67-69
verified with bisulfate dimers (HSO •••HSO ) ,
dimers of dihydrogen phosphate
4
4
2
– 70-71
2– 52
(
H PO •••H PO ) ,
and in polymerization of phosphonate monomers (RHPO •••RHPO ) ,
3 3
2
4
2
4
the investigation and development of this anion recognition chemistry into a useful tool for
supramolecular polymer-based materials is far from developed. In our previous study of
52
supramolecular polymerization driven by phosphonate dimerization, precipitation of a relatively
low molecular-weight product limited subsequent studies to better understand and elucidate the
design principles governing anion-anion driven supramolecular polymerizations.
In this present work, we leverage the inherent modularity of anion-anion dimerization to
create new supramolecular connectivities, and present the first example where stoichiometry
generates well-defined supramolecular polymers with controlled sequences. We designed a
cyanostar that is penta-substituted with triethylene glycol chains (OTgCS, Figure 1b) to overcome
the solubility issues associated with the parent cyanostar (tBuCS).72 We combined these
macrocycles with a rigid diphosphate monomer bearing two identical phosphate end-groups
connected by a single phenyl ring (Figure 1a). We discovered that the stoichiometric ratio between
building blocks controls the sequence of supramolecular linkages present in the resulting polymers
(Figure 1c). A 2:1 stoichiometry between macrocycle and diphosphate monomer produces a
supramolecular homopolymer, (A) , with repeat units of identical 2:2 anion-receptor recognition
n
6
ACS Paragon Plus Environment

Page 7 of 43
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
units. When combined in a 1:1 stoichiometry, however, two types of supramolecular linkages
arranged in an alternating sequence define an alternating copolymer (AB) . These links include
n
the pre-programmed anti-electrostatic 2:2 anion-receptor recognition of (A), and an unexpected
link, (B), based on a phosphate-phosphate dianion dimer stabilized by ion-pairing with the
tetrabutylammonium counter cations (Figure 1c). We demonstrate the use of these materials as a
new class of anion-coordination driven supramolecular polymer adhesives.73-80 The homopolymer
comprised of cyanostar-stabilized phosphate dimers is sufficiently cohesive to glue hydrophilic
glass slides together to support relatively heavy weights (10 lbs) while the alternating copolymer,
with half the links composed of cation-stabilized anion-anion dimers, shows much weaker
adhesion. We see OTgCS macrocycles are also capable of supporting strong adhesion on account
of π-stack mediated self-association of macrocycles. Putative hydrogen bonding from the glass
surface to the OTgCS macrocycle’s glycol chains operates in concert with the supramolecular
polymerization to promote the adhesion. The adhesion properties correlate to the sequences of the
supramolecular polymers allowing for the development of structure-property relationships for
anion-anion driven supramolecular polymers and design principles for anion-based materials.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Results and Discussion
Molecular Design
The OTgCS cyanostar was synthesized with five triethylene glycol chains (Scheme 1) to
enhance solubility for studying polymerization at high concentrations. Ethylene glycol chains are
also commonly incorporated into synthetic adhesives to enable strong hydrogen bonding
interactions with hydrophilic surfaces. The length of the glycol chain was designed to provide
7
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 8 of 43
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
sufficient solubility and adhesion properties without adversely impacting purification using
chromatography. The modified OTgCS macrocycle was made in good yield following the same
7
2
procedure as the parent cyanostar, tBuCS. The new cyanostar achieved the desired goals with
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
enhanced solubility in common organic solvents such as dichloromethane, acetonitrile, and
methanol, and demonstrated a similar anion-binding profile as the parent tBuCS macrocycle
–
towards both PF (Figure S11) and phenyl monophosphate (Figure S12).
6
Scheme 1. Synthetic scheme for preparation of penta-substituted cyanostar macrocycle, OTgCS.
OTg
OTg
OTg
PCC
Silica gel
I
2
Cs CO3
CuI
Pd(PPh ) Cl
CH Cl2
EtOH / THF
HO
CN
HO
CN
O
2
H
CN
3
2
2
O
THF / Et N
75%
74%
3
90%
O
O
O
OTg =
O
O
O
O
O
O
O
N
N
O
O
O
O
N
N
O
O
O
N
O
O
O
O
O
O
8
ACS Paragon Plus Environment

Page 9 of 43
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Two types of difunctional monomers were originally designed to help study the
dependence of monomer structure on polymerization. A long flexible monomer, triethylene glycol
bis(phenyl-p-phosphate), was used for initial polymerization studies. Its flexibility mimics the
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
52
dodecylene diphosphonate we used previously to demonstrate polymerization with tBuCS. This
flexible monomer was expected and found to behave similarly, providing confirmation that the
hydroxyanion dimerization could be used as pre-programmed supramolecular links with both
diphosphates as well as the original diphosphonates. To conduct structure-property studies, we
also selected a short and rigid phenylene diphosphate monomer. We initially hypothesized that it
may limit supramolecular polymerization on account of steric interactions and decreased polymer
solubility. We did not anticipate the structural difference between the two monomers would
manifest in the stoichiometric control of supramolecular polymer sequence reported herein.
2
:2 Model Complex between Phenyl Monophosphate and Cyanostar
We used the 2:2 complexation between phenyl monophosphate and the OTgCS
macrocycle as a small-molecule model of the linkage chemistry expressed in the supramolecular
1
polymers. The 2:2 complex forms with high fidelity as seen in a titration monitored by H NMR
spectroscopy (Figure S12). A number of features are similar to the complexation of phenyl
70
monophosphate with the parent cyanostar tBuCS. The uncomplexed OTgCS macrocycle shows
similar aromatic peak positions as tBuCS (Figure 2a). Upon addition of 1.0 equivalent of phenyl
monophosphate, we see a characteristic signature of the 2:2 linkage (Figure 2b). The far down-
field shifted peak at 14.7 ppm is assigned to the phosphate’s OH peak and its position is diagnostic
of the formation of a self-complementary hydrogen bond between the two phosphates and, thus,
6
7
confirmation of phosphate dimerization. The anion dimers are formed inside the cavity of π-
9
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 10 of 43
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
70
stacked macrocycles as established in previous reports. Confirmation of the macrocycle dimers
stems from the two H peaks (7.6 ppm, Figure 2b) assigned to diastereomers. Single cyanostars
c
are a racemic mixture of rapidly interconverting M and P enantiomers that are known to form into
meso (MP) and chiral (MM and PP) combinations upon 2:2 complexation.72,81 Resolution of the
two diasteromeric complexes (meso and chiral) indicates exchange between them is slow on the
NMR time scale. The formation of the 2:2 complex is also supported by diffusion NMR. The
diffusion values obtained from the cyanostar (H ) and the phenylene monophosphate (H ) are
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
c
f
identical and generate a volume that is 1.5 times larger than the free macrocycle (Figure 2d).
1
Figure 2. Representations and stacked H-NMR spectra of (a) OTgCS, (b) the small-molecule 2:2
complex, and (c) the supramolecular polymer (C) . (d) Normalized size comparisons were
n
10
ACS Paragon Plus Environment

Page 11 of 43
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
푘퐵푇
determined from diffusion coefficients based on the Stokes-Einstein equation (D = 6휋휂푟) and the
4
1
3
spherical model (V = 푟 ), V is proportional to . ([OTgCS] = 10 mM, [phenyl monophosphate]
3
3
퐷
=
10 mM, [triethylene glycol bis(phenyl-p-phosphate)] = 5 mM, CD Cl , 298 K, 600 MHz).
2 2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Supramolecular Homopolymer using the Flexible Diphosphate Monomer
To verify that the diphosphate monomers can be combined with the OTgCS macrocycle
to form supramolecular polymers, we used the flexible triethylene glycol bis(phenyl-p-phosphate)
to define homopolymers (C) . These two components were mixed at a 2:1 ratio to match the
n
equivalence point for the formation of the 2:2 macrocycle:phosphate linkage chemistry (Figure
2
c). Using the 2:2 complex as a model, we see the same diagnostic OH peaks at 14.6 ppm
indicating the formation of the encapsulated phosphate-phosphate dimers (Figure 2c). We also see
characteristic peak shifts (8.1-8.6 ppm) and the diastereomeric splitting in proton H all consistent
c
with a complexed cyanostar dimer. Together, these observations confirm the formation of the 2:2
linkage chemistry. Indicative of polymerization, the diffusion NMR shows a dramatic 35-fold
increase in size relative to the model complex (Figure 2d). This change is consistent with the 64-
fold difference seen previously with the supramolecular polymer made from tBuCS and
5
2
dodecylene diphosphonate. These results confirm that supramolecular polymerization can be
achieved using flexible monomers with reliable pre-programmed linkage chemistry composed of
cyanostar-stabilized phosphate dimers.
11
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 12 of 43
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Alternating Supramolecular Copolymer in the Solid State using Crystalline Cyanostars
We were surprised to observe a different supramolecular polymer sequence in the solid
state when using the rigid phenylene diphosphate monomer in the place of the flexible one. In this
case, the more crystalline tBuCS cyanostar was used in place of OTgCS to determine the crystal
structure of the supramolecular polymer. The crystal structure shows two different types of
phosphate-phosphate dimers (Figure 3). As expected from all prior studies, we see the 2:2 linkage
chemistry highlighted as (A). Therein, the anti-electrostatic phosphate-phosphate dimer is
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
encapsulated by two π-stacked macrocycles. The anion dimers are stabilized by a combination of
self-complementary hydrogen bonding and the CH hydrogen bonding from the cyanostars.67,70
The second type of linkage, highlighted as (B), was unanticipated. This new link is also composed
of phosphate-phosphate dimers which are not complexed by cyanostars. These dimers engage in
one direct phosphate-phosphate hydrogen bond and one methanol-bridged hydrogen bond between
the two phosphates. As with all hydroxyanion dimers, theoretical studies60-64 show that these anti-
electrostatic hydrogen bonds are insufficient alone to fully stabilize the dimers. Rather, we infer
electrostatic stabilization from the close proximity of the four tetrabutylammonium cations (TBA+).
These cations surround and enshroud the doubly charged phosphate dimers
2
–
52,67-68,70-71,82
[
(RHPO )•••(RHPO )] (Figure 3). From the six examples
previously studied using
4
4
7
1
cyanostar stabilization, only one shows this type of superstructure when dihydrogen phosphate
–
+
(
H PO ) was mixed with cyanostar and co-crystallized with an additional equivalent of TBA salt.
2 4
These types of close anion-cation contacts are more common to salts of hydroxyanion crystallized
in the absence of any receptors.83-84 In those prior cases, such as in the dimer of bisulfate
2
–
67
[
(HSO )•••(HSO )] stabilized by tetrabutylammonium, there are an equal number of charged
4 4
counter cations. In the case here, there are four cations proximal to the two exposed anions.
12
ACS Paragon Plus Environment

Page 13 of 43
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 3. Crystal packing structure of the supramolecular copolymer (AB) composed of tBuCS
n
+
macrocycles (blue tube) and phenylene diphosphate (space-filling) as TBA salts (black stick).
+
TBA counter cations encircle the uncomplexed phosphate dimers in (B) links. Structures of the
phosphate-phosphate dimer encapsulated inside paired macrocycles (A) and the methanol-bridged
phosphate-phosphate dimer (B) are highlighted.
13
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 14 of 43
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
The alternating configuration of phosphate dimers, A-B-A-B etc., is believed to come as a
result of the hierarchical assembly in the densely packed solid state. Hierarchical bond formation
dictates that the strongest bonds are formed first followed by the less stable ones. We hypothesized
that the dimers stabilized by the charge-neutral cyanostar macrocycles are stronger than ones
stabilized electrostatically by the counter cations. Consistent with this idea, cyanostar-stabilized
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
6
8
anion-anion dimers are stable in a range of conditions without relying on ion pairing. When the
receptors are not present, anion dimers demand high concentrations to form, offer more ambiguous
7
1
signatures and presumably rely on ion pairing for enhanced stabilization. Therefore, formation
of cyanostar-stabilized dimer (A) liberates two counter cations for use elsewhere in the assembly.
All together, the uncomplexed phosphate dimers (B) have four stabilizing cations. The four cations
emerge from the hierarchical assembly, which is believed to be a key step to forming the
alternating sequence in the copolymer.
The distance dependence of electrostatic interactions suggests that the length of the
phenylene linker is also important for copolymer formation. The linker is short enough to help
bring multiple negative charges close to each other to enhance the electrostatic stabilization.85-86
Consistent with this idea, use of long dodecylene diphosphonate52 or the long and flexible
diphosphate monomers fails to produce the alternating copolymer in solution or the solid state. A
competing hypothesis is that the alternating sequence emerges as a result of steric repulsion
between macrocycles. However, the phenylene linker is also long enough to accommodate all the
macrocycles. The goldilocks effect appears to be in play. The phenylene is not too big nor too
small but just right for producing the copolymer. We also attempted to form the homopolymer in
the solid state by increasing the relative amount of tBuCS macrocycles during crystallization but
without success. This specific finding suggests that the ionic interactions may be larger than
14
ACS Paragon Plus Environment

Page 15 of 43
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
expected. Thus, it was not clear from the crystal structure if the hierarchical assembly of the rigid
phenylene diphosphate into an alternating supramolecular copolymer (AB) is driven by the
n
cyanostars or the cations.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Stoichiometry-controlled Supramolecular Copolymers in Solution
Inspired by the two types of phosphate-phosphate linkages seen in the crystal structure, we
hypothesized that the alternating copolymer and homopolymer configurations could form in
solution by stoichiometry control (Figure 4a). We expected to produce the supramolecular
homopolymer (A) composed solely of pre-programmed cyanostar-stabilized phosphate dimers by
n
using a 2:1 stoichiometric ratio between macrocycle and phenylene diphosphate. Adjusting the
stoichiometry to a 1:1 ratio would then be expected to form the alternating supramolecular
copolymer (AB) seen in the solid state.
n
Figure 4. (a) Representation for the stoichiometry-controlled supramolecular polymerization. (b)
1
Stacked H-NMR spectra of OTgCS, supramolecular homopolymer (A) , and alternating
n
15
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 16 of 43
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
copolymer (AB) ([OTgCS] = 5 mM, CD Cl , 298 K, 600 MHz). (c) Relative peak intensity
n
2
2
changes of the free macrocycle, the supramolecular homopolymer (A) , the alternating
n
supramolecular copolymer (AB) and intermediate species as a function of increasing amount of
n
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
phenylene diphosphate.
As anticipated, we were able to use stoichiometry to prepare both types of supramolecular
polymers; the (A) homopolymer and (AB) copolymer. Significantly, the OTgCS macrocycle
n
n
provided the increased solubility needed to explore stoichiometry control. Elevated concentrations
were not possible using tBuCS on account of significant precipitation at the 2:1 ratio beyond 5
mM. The OTgCS macrocycle was mixed with 0.5 equivalents of the phenylene diphosphate
monomer to achieve the 2:1 ratio for homopolymerization to form (A) . The diagnostic OH peak
n
at 13.7 ppm indicates the presence of encapsulated phosphate-phosphate dimers in the
supramolecular homopolymer (A) . Broad peaks (Figure 4b, middle) in the 7-9 ppm region, which
n
do not match the sharp peaks (Figure 2c) seen in the homopolymer with the long flexible
diphosphate (C) , instead suggest the formation of large aggregates. This interpretation is
n
consistent with the small diffusion coefficient (1.0 ± 0.2 × 10–10 m / s, 5 mM) consistent with 47-
2
fold larger volume relative to the 2:2 model complex (3.7 ± 0.1 × 10–10 m / s, 5 mM).
2
Addition of slightly more diphosphate monomer (e.g., 0.7 equivalents) leads to production
of a more complicated spectrum (Figure S14) attributed to a species of intermediate sequence. We
see decreasing intensity in peaks corresponding to the supramolecular polymer (A) around 7.3
n
ppm (H ) and the OH peak at 13.7 ppm. At the same time, a new species is produced represented
c
by H peaks around 7.4 and 7.5 ppm as well as two OH peaks emerging at 14.3 and 14.6 ppm.
c
These observations indicate that the encapsulated phosphate-phosphate dimers are in different
16
ACS Paragon Plus Environment

Page 17 of 43
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
chemical environments at this intermediate molar ratio. The sequences associated with this
intermediate likely sit between those of the supramolecular homopolymer (A) and copolymer
n
(AB)n.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
In order to achieve the correct mole ratio to produce the alternating copolymer (AB) , we
n
added 1.0 equivalent of phenylene diphosphate. Clear cyanostar-based peaks characteristic of the
2
:2 linkage chemistry, (A), were observed (Figure 4b, bottom). Again, the diffusion coefficient
2
(
1.2 ± 0.1 × 10–10 m / s) based on peaks in the aromatic region was much smaller than that of the
2:2 complex (3.7 ± 0.1 × 10–10 m / s), corresponding to a species that is 27-fold larger. The OH
peak at 14.6 ppm confirms the phosphate-phosphate dimers are encapsulated inside the cyanostar
dimers. The hydrogen-bonded OH protons of the uncomplexed phosphate-phosphate dimers
2
1
71
cannot be identified from the H NMR spectra. This finding is consistent with previous studies
–
involving complexation of dihydrogen phosphate H PO dimers and trimers with tBuCS.
2
4
Diagnostic of the structure of the alternating copolymer, we see the phenylene monomer’s
symmetry is broken and gives rise to two peaks of equal intensity at 6.5 and 6.4 ppm. (Figure S18).
3
1
We also see two peaks in the P NMR spectra (Figure S20). Consistently, we only see one
resonance from the homopolymer (A) . The two different chemical environments coincide with
n
the crystal packing structure of the alternating copolymer (AB) (Figure 3).
n
1
1
Structural evidence for the alternating copolymer is provided from the H- H NOESY
correlations. First, we observe a crosspeak from the phenylene ring of the diphosphate monomer
+
(
Figure 5, H , H ) to the protons (H ) on the TBA counter cations indicative of the ion-pairing
1
2

interactions expected for the unencapsulated phosphate-phosphate dimers. These ion-pair
interactions must be reasonably long lived to generate NOE crosspeaks. This cross peak is not seen
1
1
in the homopolymer (A) . Correlation peaks in the H- H NOESY plot (Figure S30) between the
n
17
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 18 of 43
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
protons inside macrocycles cavity (H , H ) and on the phenylene diphosphate (OH, H , H ) also
a
d
1
2
support formation of the cyanostar-stabilized phosphate dimer. All these results are consistent with
the two different forms of the phosphate-phosphate dimers in the alternating copolymer. If instead
a random or statistical sequence was present, e.g., AABABBBA, we would expect a larger number
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
of H NMR peaks associated with the greater variety of chemical environments. As we only see
two major peaks for the phenyl ring of the phenylene diphosphate in a 1:1 ratio, an alternating
copolymer is supported.
1
1
Figure 5. Partial H- H NOESY spectra of the alternating copolymer shows correlations between
+
TBA cation and the phenylene diphosphate monomers. ([OTgCS] = 5 mM, CD Cl , 298 K, 500
2
2
MHz).
18
ACS Paragon Plus Environment

Page 19 of 43
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
To the best of our knowledge, this is the first time that stoichiometry has been shown to
control the sequence of supramolecular polymers. We can plot the species variation as a function
of stoichiometry using the signatures assigned to the homopolymer (A) and alternating copolymer
n
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
AB) (Figure 4c). For this speciation plot, we used a combination of the OH peaks and the
n
aromatic peaks in the 7.0-7.6 ppm region to determine relative peak intensities (Figure S14). We
also include the intermediate species by using the OH peak at 14.3. In the speciation curve (Figure
4
c), we see the supramolecular homopolymer (A) dominates at 2:1 stoichiometry (0.5 equivalents)
n
and the alternating copolymer (AB) dominates at the 1:1 stoichiometry (1.0 equivalent).
n
In order to understand the concentration-dependence for the stoichiometry-controlled
supramolecular polymerization, we repeated the titrations at lower ([OTgCS] = 0.5 mM) and
higher ([OTgCS] = 50 mM) concentrations (Figure S16 and S17). We see the distribution of
species largely remains the same with increasing concentration.
Concentration-driven Supramolecular Polymerization
Increasing the concentration of monomers is known to drive supramolecular
n
polymerization. Consistently, diffusion NMR studies show the size of the both (A) and (AB)n
polymers show a 21-fold and 87-fold volume change from 1 mM to 50 mM, respectively (Figure
6
a). For the phenylene diphosphate alone, however, diffusion coefficients show a small decrease
indicating a 2.6-fold volume change consistent with a previous study for the dodecylene
diphosphonate.52 These results suggest that cyanostar-stabilized anion-anion dimers are
responsible for the driving force of supramolecular polymerization. We also see the diffusion
coefficients for the (AB) copolymer becomes larger than (A) at concentrations above 50 mM.
n
n
This result is consistent with increased ion pairing helping to stabilize the uncomplexed phosphate-
19
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 20 of 43
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
phosphate dimers at higher concentrations. We also see from these results that the diffusion
coefficient of the OTgCS macrocycle decreases over this concentration range. This behavior is
indicative of self-association facilitated by π-π interactions between the faces of OTgCS
macrocycles. Variable concentration studies followed by NMR spectroscopy show that this
macrocycle aggregates more than the parent cyanostar consistent with the role of glycol chains in
stabilizing self-associated stacks of shape persistent macrocycles (Figure S9).87-88
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 6. (a) Changes of diffusion coefficients of the phenylene diphosphate, OTgCS, and
OTgCS with 0.5 equiv. and 1.0 equiv. of phenylene diphosphate with increasing concentration.
(b) Specific viscosity of the homopolymer and the alternating copolymer versus concentration
change in mg / mL (dichloromethane, 298 K, 600 MHz).
20
ACS Paragon Plus Environment

Page 21 of 43
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
To further verify the concentration-driven polymerization, we conducted specific viscosity
measurements (Figure 6b). The double-logarithmic plots of specific viscosity versus concentration
for supramolecular polymers (A) and (AB) display slopes of 1.30 and 1.39, respectively. We see
n
n
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
the alternating copolymer shows a slightly larger slope than the homopolymer suggesting the
8
9
alternating copolymer is more likely to be physically entangled. A turning point in these plots
are sometimes observed and then assigned to the critical polymerization concentration (CPC).90
The absence of such a point over the concentration range examined here suggests that (A) and
n
(
AB) are already above the CPC for both polymers. This type of behavior has been seen
n
previously in supramolecular polymers that were promoted by rigid monomers.17,45
Stoichiometry-controlled Adhesion Properties of the Supramolecular Polymers
Structure-property relationships can be established by correlating the different
supramolecular polymer sequences, (A) and (AB) to their adhesive properties. In contrast to the
n
n
supramolecular polymer based on the parent macrocycle tBuCS, we did not observe precipitation
when using OTgCS thereby allowing for further study of its bulk properties. The supramolecular
polymers derived from OTgCS are sticky and viscous at high concentration. Inspired by this
7
3
observation and other supramolecular polymer adhesives, we hypothesized that the OTgCS-
based supramolecular polymers could be used as adhesive materials. Specifically, for binding
hydrophilic surfaces together (Figure 7a), such as glass, on account of OH•••O hydrogen bonding
from surface hydroxyls (SiOH) to the ether oxygens in the triethylene glycol chains of the OTgCS
macrocycle (Figure 7b).74,78
21
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 22 of 43
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
Each supramolecular polymer was used to coat glass slides with a 2.5 × 2.5 cm overlap
area and the resulting slides were used to support weights for initial adhesion testing (Figure 7c).
We observed that the OTgCS macrocycle alone is capable of supporting a 10-lb weight (Figure
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
7
c, left). This behavior is attributed to the self-aggregation of OTgCS macrocycles seen in the
1
variable concentration studies monitored by diffusion NMR (Figure 6a) and H NMR spectroscopy
(
Figure S9). Assuming the π-stacking between OTgCS macrocycles dominate the self-assembly,
the triethylene glycol chains are free to interact with the hydrophilic surface through hydrogen
bonding. Pull-off (Figure 8a) and lap-shear (Figure S35) adhesion tests were performed to quantify
the adhesion strength of OTgCS (Table 1). The OTgCS macrocycle shows strong pull-off tensile
strength of 3.6 ± 0.4 MPa and shear strength of 1.6 ± 0.6 MPa. For comparison, the tBuCS
macrocycle did not display any adhesive properties, which supports the significant role of the
triethylene glycol chains in adhesion.
22
ACS Paragon Plus Environment

Page 23 of 43
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 7. (a) Schematic procedure of preparing adhesive samples using glass slides. (b)
Representation of the hydrogen bonding interaction between hydrophilic glass surface and the
triethylene glycol chains from OTgCS macrocycles on the polymer. (c) Photographs showing
adhesion behavior of OTgCS, the 2:2 complex of OTgCS and phenyl monophosphate, and the
supramolecular homopolymer of (A) using the phenylene diphosphate, respectively. Adhesive
n
sample loading is 10 mg, and loading area is 2.5 × 2.5 cm2.
23
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 24 of 43
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
For the small-molecule 2:2 complex between the OTgCS macrocycle and phenyl
monophosphate, we observed very weak adhesion that only supported a 1-lb weight (Figure 7c,
middle), with a pull-off adhesion strength of 0.5 ± 0.2 MPa, and shear strength of 0.2 ± 0.1 MPa
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(Table 1). The weaker adhesion strength is consistent with loss of macrocycle self-association
upon complexation. This change from associated state to a complex has been seen with a related
6
9
tricarbozole macrocycle that displays a high degree of self-association. Thus, while the hydrogen
bonding between the surface and the glycol chains is important for strong adhesion when using
the OTgCS macrocycles, addition of the custom-designed organophosphate anions to drive
formation of 2:2 complexes is insufficient to create an adhesive material.
Table 1. Quantitative adhesion strength of supramolecular polymers, control monomers, 2:2
complex, commercial glues and other supramolecular polymer adhesives. a
Pull-off strength
MPa)
Lap-shear strength
(MPa)
Sample
(
OTgCS
3.6 ± 0.4
0.5 ± 0.2
4.2 ± 0.4
0.9 ± 0.2
2.4 ± 0.3
5 ~ 9
1.6 ± 0.6
0.2 ± 0.1
2.0 ± 0.5
0.4 ± 0.2
1.1 ± 0.2
2:2 complex
(
A)n
AB)n
C)n
(
(
–
––
Superglue
–
––
White glue
0.4
Hydrogen bonding driven
–
––
4
.2
b
SPs
Metal-coordination
–
––
2
.5
c
SPs
24
ACS Paragon Plus Environment

Page 25 of 43
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
a
2 b
Sample loading of tested materials is about 10 mg, loading area is 2.5 × 2.5 cm . Hydrogen
bonding driven supramolecular polymer using triply benzo-21-crown-7-substituted 1,3,5-
benzenetricarboxamides.74 c Metal-coordination driven supramolecular polymer based on iron
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
coordinated poly(thioctic acid diisopropenylbenzene).78
Strong adhesion is expected from the supramolecular polymers where the 2:2 linkages are
now covalently linked together. Consistently, we see the supramolecular homopolymer (A)n
supports a 10-lb weight (Figure 7c, right), with a pull-off strength of 4.2 ± 0.4 MPa (Figure 8b).
This adhesion strength is comparable to supramolecular adhesive made using
74
benzenetricarboxmide triply substituted with benzo-21-crown-7 (4.2 MPa), and which relies on
hydrogen bonding linkages. By doing a single lap-shear test, we see the supramolecular
homopolymer shows a shear strength (2.0 ± 0.5 MPa), which is comparable to a metal coordination
driven supramolecular copolymer based on poly(thioctic acid diisopropenylbenzene) (2.5 MPa).78
It is clear from this performance that anion-driven supramolecular polymers display adhesion
properties that match supramolecular polymers supported by more traditional linkage chemistries.
Nevertheless, it is counterintuitive that the strong adhesion arises from linkage chemistry involving
two like charges. These linkages are expected to repel each other and inhibit, instead of enhance,
adhesion. The fact that this expectation is not fulfilled is remarkable and underscores the role of
cyanostar recognition in helping reshape the terms of conventional wisdom.
In the case of the alternating copolymer (AB) , exactly half of the cyanostar-stabilized
n
linkages are replaced by cation-stabilized linkages such that every other phosphate-phosphate
dianion (2–) is stabilized by four proximal cations (4+). This system falls squarely in the realms
of our conventional wisdom where the attraction between opposite charges is expected to
25
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 26 of 43
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
contribute to significant stabilization in the solid state. Furthermore, solids typically support closer
contacts and lower dielectric constants than solutions. From Coulomb’s law, therefore, this ionic
bonding is expected to be substantial. It is not clear a priori, therefore, if the bulk samples of the
homopolymer (A) or the copolymer (AB) would have stronger adhesion.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
n
n
Figure 8. (a) Representation of the pull-off strength test for adhesive samples. (b) Pull-off strength
of OTgCS, the 2:2 complex between OTgCS and phenyl monophosphate, the supramolecular
homopolymer (A) , and the copolymer (AB) using the phenylene diphosphate. (c) Representation
n
n
26
ACS Paragon Plus Environment

Page 27 of 43
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
of tunable supramolecular polymer adhesives made from a two-pot mix into either the superglue
grade homopolymer or white glue grade copolymer.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
A much weaker adhesion strength was observed for the alternating supramolecular
copolymer (AB) than the homopolymer (A) . A pull-off strength of 0.9 ± 0.2 MPa and a shear
n
n
strength is 0.4 ± 0.2 MPa were observed (Figure 8b). The copolymer is only about 20% the
adhesion strength of the homopolymer. This observation strongly suggests that the linkage defined
by cyanostar-stabilized anti-electrostatic phosphate dimers are stronger than the cation-stabilized
phosphate dimers.
To provide some support for the roles of cyanostar-stabilized and cation-stabilized anion-
anion linkages, we conducted a series of control studies. To enhance the electrostatic driving force,
+
we added extra TBA salts and consistently saw increases in the adhesion strength (Figure S32) of
the alternating copolymer. To test for the role of the cyanostar in adhesion, we evaluated a neat
film of the phenylene diphosphate monomer alone. No adhesion was observed, which is attributed
to the absence of surface-active glycols. To emulate the surface interaction, we mixed the rigid
–
1
monomer with 1 equivalent of polyethylene glycol of a molecular weight (M = 2000 g mol )
w
matching two cyanostars used in homopolymer (A) . No adhesion was observed in this case either
n
(Figure S33). These results support the finding that the anion-anion linkages also benefit
substantially from cyanostar stabilization. We evaluated the adhesion strength (Table 1) of the
supramolecular polymer (C) composed of the flexible triethylene glycol bis(phenyl-p-phosphate)
n
and found it is about half that of (A) despite having the same amount of cyanostar in each case.
n
This result suggests that the compact character of the supramolecular polymer chain in (A)n
provides better support for adhesion.
27
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 28 of 43
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Reversible and Tunable Adhesion
The adhesion properties of the supramolecular homopolymer (A) are thermally reversible.
n
o
A 10-lb weight was released by external heating (~50-60 C) of the bonded glass slides for ~30 s
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(Figure S34). We observe that both faces of the debonded glass slides retain some of the
supramolecular adhesive material indicating that the debonding occurred within the adhesive
material. This heat-induced debonding can be attributed to either the loss of physical entanglement
mediated by the glycol chains on the OTgCS macrocycles and/or the dissociation of the 2:2
supramolecular linkages upon heating. The adhesion strength could be recovered by overlapping
the two slides together and storing them under vacuum for 1 hour. Presumably, the supramolecular
polymer is able to dynamically reform at the physically contacted interface. This reversible process
could be repeated for a few cycles without losing the base adhesion strength.
On account of the dynamic and stimuli-responsive characteristics of supramolecular
linkages, the reusability91-93 we showed here or interfacial self-healing properties14,94-95 are typical
features of supramolecular polymer adhesives. However, to the best of our knowledge, this is the
first report that demonstrates a supramolecular polymer with tunable adhesion strength based on
controlling the polymer sequence (Figure 8c). Specifically, the homopolymer (A) shows
n
comparable adhesion strength to commercial superglue formulations based on polycyanoacrylate
7
3
(
5~9 MPa, Table 1), while the adhesion strength of the copolymer (AB) is comparable to white
n
7
4
glue based on poly(vinyl acetate) (0.43 MPa, Table 1). Thus, we can tune the adhesion strength
of the supramolecular polymer between that of superglue and white glue simply by changing the
stoichiometric ratio of the monomers (Figure 8c). Consistently, we also see an intermediate
mixture of cyanostar with 0.75 equivalent of phenylene diphosphate shows a 2.1 ± 0.3 MPa pull-
off strength and 0.9 ± 0.2 MPa lap-shear strength. The properties stem directly from the sequence-
28
ACS Paragon Plus Environment

Page 29 of 43
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
defined structures and the strengths of the supramolecular linkage chemistries. This study provides
a new way to understand how material properties reflect structural information in the form of
anion-driven supramolecular polymer adhesives.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Conclusions
We discovered a new form of sequence control in supramolecular polymers based on
diphosphate monomers of compact size mixed with cyanostar macrocycles to drive phosphate-
phosphate dimerization. With a 2:1 stoichiometry, a supramolecular homopolymer (A) is
n
produced that is composed of phosphate-phosphate dimers inside π-stacked cyanostar macrocycles.
At a 1:1 stoichiometry, the alternating supramolecular copolymer (AB) is co-driven by cyanostar-
n
stabilized phosphate dimers and cation-stabilized phosphate dimers. The cation-stabilized dimers
emerge hierarchically from the superstructure in which the stronger primary cyanostar-stabilized
linkages liberate extra cations that are used to reinforce the secondary ionic linkage. The two types
of anion-anion dimers constitute orthogonal linkage chemistries, which are required to elicit
sequence control. This study further demonstrates the utility of anion-anion dimerization to
synthesize functional and tunable supramolecular polymers. This is the first time that these
linkages have been transformed into a polymer capable of supporting materials properties
expressed here as adhesion. The supramolecular homopolymer (A) displays strong adhesive
n
properties, whereas the alternating supramolecular copolymer (AB) has less adhesion strength.
n
Here we see expression of the remarkable idea that sum of attractive driving forces in the anion-
anion linkages overcome their repulsions when stabilized by complementary cyanostar receptors
to a greater extent than traditional ionic contacts. Thus, the adhesion strength of the supramolecular
polymers is composition-dependent, which corresponds directly to the stoichiometry- and
29
ACS Paragon Plus Environment