Dictating Nanoparticle Assembly via Systems-Level Control of Molecular Multivalency

Article abstract of DOI:10.1021/jacs.9b04999

Nanoparticle assembly can be controlled by multivalent binding interactions between surface ligands, indicating that more precise control over these interactions is important to design complex nanoscale architectures. It has been well-established in natural materials that the arrangement of different molecular species in three dimensions can affect the ability of individual supramolecular units to coordinate their binding, thereby regulating the strength and specificity of their collective molecular interactions. However, in artificial systems, limited examples exist that quantitatively demonstrate how changes in nanoscale geometry can be used to rationally modulate the thermodynamics of individual molecular binding interactions. As a result, the use of nanoscale design features to regulate molecular bonding remains an underutilized design handle to control nanomaterials synthesis. Here we demonstrate a polymer-coated nanoparticle material where supramolecular bonding and nanoscale structure are used in conjunction to dictate the thermodynamics of their multivalent interactions, resulting in emergent bundling of supramolecular binding groups that would not be expected on the basis of the molecular structures alone. Additionally, we show that these emergent phenomena can controllably alter the superlattice symmetry by using the mesoscale particle arrangement to alter the thermodynamics of the supramolecular bonding behavior. The ability to rationally program molecular multivalency via a systems-level approach therefore provides a major step forward in the assembly of complex artificial structures, with implications for future designs of both nanoparticle- and supramolecular-based materials.

Full text of DOI:10.1021/jacs.9b04999

Subscriber access provided by Macquarie University
Article
Dictating Nanoparticle Assembly via Systems-
Level Control of Molecular Multivalency
Peter J Santos, Zhen Cao, Jianyuan Zhang, Alfredo Alexander-Katz, and Robert J. Macfarlane
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b04999 • Publication Date (Web): 29 Aug 2019
Downloaded from pubs.acs.org on August 29, 2019
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 10
Journal of the American Chemical Society
1
2
3
4
5
6
7
Dictating Nanoparticle Assembly via Systems-Level Control of Mo-
lecular Multivalency
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
Peter J. Santos, Zhen Cao, Jianyuan Zhang†, Alfredo Alexander-Katz, and Robert J. Macfarlane*
Department of Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cam-
bridge, Massachusetts 02139, United States
ABSTRACT: Nanoparticle assembly can be controlled by multivalent binding interactions between surface ligands, indicating that
more precise control over these interactions is important to design complex nanoscale architectures. It has been well-established in
natural materials that the arrangement of different molecular species in three dimensions can affect the ability of individual supramo-
lecular units to coordinate their binding, thereby regulating the strength and specificity of their collective molecular interactions.
However, in artificial systems, limited examples exist that quantitatively demonstrate how changes to nanoscale geometry can be
used to rationally modulate the thermodynamics of individual molecular binding interactions. As a result, the use of nanoscale design
features to regulate molecular bonding remains an underutilized design handle to control nanomaterials synthesis. Here, we demon-
strate a polymer-coated nanoparticle material where supramolecular bonding and nanoscale structure are used in conjunction to dictate
the thermodynamics of their multivalent interactions, resulting in emergent bundling of supramolecular binding groups that would
not be expected if considering the molecular structures alone. Additionally, we show that these emergent phenomena can controllably
alter superlattice symmetry by using mesoscale particle arrangement to alter the thermodynamics of supramolecular bonding behav-
ior. The ability to rationally program molecular multivalency via a systems-level approach therefore provides a major step forward
in the assembly of complex artificial structures, with implications for future designs of both nanoparticle and supramolecular-based
materials.
Introduction
the opposite direction, where large-scale organization alters the
behavior of individual building blocks (e.g. nanoscale organi-
zation affecting molecular multivalency). Methods to control
hierarchical organization via interplay between structures both
up and down multiple length scales simultaneously can be re-
ferred to as a “systems” approach to materials development.
Nanoparticle assembly is commonly regulated by multivalent
intermolecular binding events between surface ligands, where
the collective interaction of multiple surface-bound molecules
1
dictates the overall thermodynamics of interparticle bonding.
A significant amount of effort has therefore been put forth in
examining how alterations to these molecular interactions affect
nanoparticle behavior, and many strategies have been devel-
oped to control particle arrangements by finely tuning the mo-
lecular structures that guide nanoparticle assembly. However,
while the manipulation of molecular bonding has been shown
to be a powerful means to control the thermodynamics of na-
noscale assembly, it is also true that the nanoscale arrangement
of these molecular binding groups can affect the overall strength
of the bonds being formed. In other words, not only can
changes to molecular geometry alter material ordering at larger
length scales, but changes to these larger scale structures can
also cause alterations to molecular behavior. Indeed, manipu-
lating the relative positions of individual chemical moieties is a
common design principle used in nature to control the strength
and specificity of multivalent intermolecular interactions in-
cluding avidity in antibody-antigen binding, substrate selec-
tivity at the active site of catalytic enzymes, and strong yet
dynamic carbohydrate-regulated cell adhesion. While syn-
thetic materials typically try to general hierarchical ordering
from small length scales upwards (e.g. changes to molecular
motifs causing different nanoscale behaviors), these examples
in nature demonstrate that structural hierarchy can also work in
In principle, it should be possible to develop a systems-level
approach to nanoparticle assembly, where structural features at
the length scales of individual molecular bonds, nanoscale par-
ticle geometry, and mesoscale arrangement of particles serve as
2
–5
13–15
integrated design handles to control the assembly process.
For example, a systems-level approach to nanomaterials syn-
thesis could use multivalent supramolecular bonding to dictate
how nanoscale particles form into mesoscale lattices, but also
simultaneously use the nanoparticle coordination environment
within those lattices to regulate the multivalency of molecular
interactions and alter the strength of these bonds. The advantage
of such a complex materials synthesis method would be the
ability to more finely tune both particle assembly and supramo-
lecular bonding by design features both above and below the
length scales of the nanoparticle bonds themselves. In order to
realize this goal, however, it is important first to understand
how nanoscale structure affects the thermodynamics of these
multivalent interactions in a rational manner. In this work, the
hierarchical nature of a nanoparticle building block is used to
methodically modify the degree to which supramolecular
groups act collectively, and therefore control the overall inter-
action strength between nanoparticles.
6
–9
10
11
12
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 10
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
This enables a systems-level approach to materials synthesis,
where nanoscale geometry influences molecular organization,
and those design parameters in conjunction control mesoscale
architecture, affording simultaneous control of material struc-
ture across multiple length scales in a programmable manner.
Results and Discussion
We have recently demonstrated a new nanoparticle-based
building block capable of directed assembly via complementary
hydrogen bonding motifs called the Nanocomposite Tecton
1
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
(NCT). NCTs consist of rigid nanoparticle cores functional-
ized with deformable polymer chains in a dense brush architec-
ture (Figs. 1, S1-S5, S8; NCTs examined here consist of gold
nanoparticles coated in polystyrene brushes, suspended in tolu-
ene). All polymer chains on the NCTs terminate in either a dia-
minopyridine or thymine group (DAP and Thy, Scheme S1),
1
7,18
which constitute a complementary supramolecular pair.
Complementary sets of NCTs can form many DAP-Thy com-
plexes that behave as a collective nanoscale bond linking NCTs
together into large superlattices. Indeed, with appropriate ther-
mal annealing, NCTs can even form crystalline lattices with
long-range ordering.
Each nanoscale NCT-NCT bond within these lattices is a mul-
tivalent structural feature, where the multivalency number (N)
is the number of monovalent DAP-Thy complexes that act in a
coordinated manner when two adjacent NCTs form an interpar-
1
9,20
ticle bond.
As a result, the free energy driving NCT assem-
bly can be regulated by modifying NCT structure at either the
molecular or nanometer length scales; the former controls the
strength of each individual monovalent supramolecular com-
plex, while the latter regulates how many supramolecular inter-
actions constitute a multivalent NCT-NCT bond. These syn-
thetically independent design handles at different size regimes
make NCTs ideal for exploring how both nanoparticle assembly
and the multivalency of individual NCT-NCT bonds are af-
fected by changes in structure at both the chemical and nanome-
ter length scales. The ability to rationally program multivalency
as a function of nanoscale structural features is therefore the
first step in understanding and using this systems-level ap-
proach to materials design.
Initial work has demonstrated that the collective binding en-
thalpy of an NCT-NCT bond is significantly greater than an in-
Figure 1. Typically, hierarchical structuring is understood as mo-
lecular structures causing the organization of larger length scale
motifs, but these larger motifs can also influence how the smaller
length scale components of a material behave. For example, NCTs
functionalized with DAP or Thy terminated polymer chains engage
in supramolecular bonding determined by the chemical identity of
the ligands (molecular structures, bottom). The binding groups
cluster into supramolecular bundles due to differences in intermo-
lecular forces between the head groups, polymer chains, and sol-
vent molecules (supramolecular structures), and this bundling al-
lows multiple molecular groups to act multivalently. Multiple bun-
dles arranged around a nanoparticle surface (nanoscale structures)
thereby drive the formation of ordered arrays of nanoparticles
1
6
dividual DAP-Thy complex, a hallmark of a multivalent inter-
action. However, the calculated values of multivalency for these
NCT systems are surprisingly low. For example, NCTs consist-
ing of 26 nm particle cores functionalized with ~1000 polymer
chains exhibit a multivalency value of only 10. While it is pos-
sible that each multivalent NCT-NCT bond consists of only 10
DAP-Thy complexes, the high local concentration of 100s of
DAP and Thy groups between particles makes this explanation
of a low multivalency number unlikely. An alternative reason
for this low value of N could be that the total number of DAP-
Thy complexes comprising each NCT-NCT bond is signifi-
cantly greater than 10, but there exists a structural feature in
between the nanoscale shape of the NCT and the individual mo-
lecular groups that regulates the number of complexes that can
act in a coordinated, multivalent manner. More simply, each
NCT-NCT bond consists of a large number of DAP-Thy com-
plexes, but these complexes are arranged in tiny “bundles”, and
only complexes within a single bundle could be considered to
be multivalent (Fig. 1b, right panel). Prior work has demon-
strated that given an appropriate driving force, small molecule
(mesoscale structure). However, the organization of particles
within a mesoscale lattice can in turn affects the nanoscale arrange-
ment of polymer chains surrounding each particle, and these alter-
ations affect polymer chain dynamics, which thereby modulate the
thermodynamics of the bundled molecular bonds. As a result, the
structure of the entire system must be considered simultaneously to
fully understand the different levels of hierarchical organization.
ACS Paragon Plus Environment

Page 3 of 10
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
nanoparticle cores, and the transient nature of supramolecular
complexes, the bundle bond hypothesis was first examined us-
ing molecular dynamics simulations to determine the most
probable arrangement of individual DAP-Thy complexes
within a multivalent NCT-NCT bond (Fig. 2). A full atomistic
description of NCTs would be computationally prohibitive, but
a coarse-grained model with a consistent mapping of the geom-
etry, volume fraction, and interaction parameters between ex-
periments and simulations (see SI for details, Figs. S12, S20) is
sufficient to provide insight into the configuration of the multi-
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
21,22
valent NCT-NCT bond interface.
In a typical simulation where a pair of complementary NCTs is
allowed to reach equilibrium, DAP and Thy groups that are not
part of a supramolecular complex are randomly positioned at
the periphery of the particles. However, DAP-Thy complexes
that are part of a multivalent NCT-NCT bond do indeed coa-
lesce into “bundles” that dynamically change shape throughout
the simulation (Fig. 2a, Fig. S13-S15). Thus, each multivalent
NCT-NCT bond consists of multiple “bundle bonds”, where the
degree of multivalency is determined by the number of DAP-
Thy complexes that comprise a single bundle. Because the bun-
dles are only found at the interface of NCTs connected via a
multivalent NCT-NCT bond (Fig. 2b), these data not only con-
firm the presence of the bundle bonds, but also demonstrate that
it is the act of forming a nanoscale NCT-NCT bond itself that
drives supramolecular bundle formation. NCTs therefore pre-
sent a previously unexplored opportunity to systematically
study how nanoscale structure can be used to modulate molec-
ular multivalency.
Figure 2. Molecular dynamics simulations of NCT assembly. (a)
The equilibrium structure of modeled NCTs shows the presence of
bundles that emerge at the interface of two complementary NCTs.
The dots in the inset denote positions of individual supramolecular
groups at the NCT-NCT interface; the different colors denote al-
gorithmically defined bundles that dictate the degree of multiva-
lency (see SI for clustering analysis). (b) A pair distribution func-
tion (PDF) analysis of the distance between supramolecular
groups both at and away from the NCT-NCT interface. At the in-
terface, the supramolecular binding groups associate into bundles,
resulting in a distinct spike in the PDF, which corresponds with
the radius of the bundles. The absence of this peak away from the
interface confirms that it is the act of forming the nanoscale NCT-
NCT bond that drives formation of this emergent structural fea-
ture.
It is also important to note that this bundling behavior is distinct
from previous examples of spontaneous symmetry breaking in
the ligands of nanoparticles being assembled. These differences
stem from the fact that the bundles of supramolecular com-
plexes observed here are significantly smaller than the cross-
section of the overall NCT-NCT bond, and any given NCT-
NCT bond therefore consists of multiple bundles. Moreover, the
DAP-Thy connections are dynamic, and the exact sizes and
shapes of the bundles are constantly changing. As a result, the
bundling phenomenon is not entirely identical to the “patchi-
ness” observed in other systems such as those that are aniso-
23,25
tropically functionalized
or that form soft skyrmions via lig-
2
6
and rearrangement, as the overall surface of the NCT would
still be considered to be largely isotropic even with the bundling
phenomena occurring (vide infra). This distinction means that
NCTs are affecting material structuring at a level in between an
individual molecular bond and an overall nanoparticle structure.
The obvious question that therefore arises is whether design
handles at both the molecular and nanoscale can be used in con-
junction to modulate the collective size and dynamic behavior
of these bundle bonds.
ligands on the surface of nanoparticles will indeed bundle to-
2
1,22
gether.
Similarly, polymer brushes on nanoparticles have
also been shown to engage in bundling when exposed to a
strong antisolvent.23 Based on these prior observations, we hy-
pothesize that the driving force behind bundling of supramolec-
ular complexes here could be differences in the chemical poten-
tial between individual DAP and Thy groups and the surround-
ing solvent molecules. Nonpolar polymers modified with
telechelic polar moieties are known to form reverse micelles in
low polarity solvents (Fig. S11), which would be consistent
In order to properly answer this question, it is important to un-
derstand how the thermodynamics of NCT assembly change as
a function of different nanoscale structural features. In a stand-
ard multivalent bond between NCTs, the strength of each supra-
molecular complex (each monovalent binding event) is de-
scribed by the free energy equation:
2
4
with small clusters forming at the ends of the polymer brush.
If such bundling were indeed dictating the multivalency in these
NCT systems, the presence of these “bundle bonds” would
therefore represent a systems-level emergent phenomenon
where the nanoscale sizes and shapes of the NCT could be used
to regulate thermodynamics of supramolecular complexation.
ΔG
s
= ΔH
s
– TΔS
s
(1)
Because the positions of individual chain ends on an NCT can-
not be readily measured due to their small size, their poor elec-
tron density contrast with the surrounding polymer and solvent,
the presence of the significantly larger and more electron dense
where ΔG
s
, ΔH
s
, and ΔS
s
are the Gibbs free energy, enthalpy,
and entropy associated with the formation of a single DAP-Thy
complex. The strength of a multivalent “bundle bond” is there-
fore:
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 10
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. Thermodynamics of bundle bond formation are controlled via nanoscale design handles. (a) The thermodynamics of bundle bond
formation are dictated by the number of supramolecular groups that can cluster together, as well as the entropy penalty associated with
confining polymer chain motion upon forming a supramolecular complex. In the case of a smaller particle with a short polymer the number
of supramolecular bonds is limited (left). When a longer polymer is used (right) the multivalency increases, but with an added entropic
penalty. (b) Thermal melt analysis shows increases in ΔH
decrease in NCT curvature results in a higher density of supramolecular binding groups, and therefore a larger number of hydrogen bonds
can bundle together (c) NCT T decreases with increasing polymer length for all particle sizes examined (black traces), but the collective
ΔH of the bonds either increases or decreases depending on the inorganic particle core diameter (blue traces).
m m
and T with increasing nanoparticle diameter (decreased particle curvature). A
m
m
ΔG = ΔH
m
m
– TΔS
m
(2)
m s s
bundle bond (i.e. ΔH = NΔH ). However, ΔS is not equivalent
for all polymers within a bundle bond, as different polymers
will have different amounts of conformational confinement
upon the formation of a DAP-Thy complex, depending on
where they are anchored on the surface of the nanoparticle core.
As a result, expressing the value of ΔG as a function of N, ΔH ,
where ΔG
m
, ΔH
m
, and ΔS are the Gibbs free energy, enthalpy,
m
and entropy of the collective bundle. By definition, the ratio be-
tween the enthalpy values of these reactions is the value of mul-
tivalency (i.e. N = ΔH /ΔH ). More simply, the multivalency
m s
number N is the average number of groups within a given bun-
dle.
m
s
and ΔS becomes:
s
ꢁ
ΔG
m
= N(ΔH
s
) – T �∑ ΔS ꢂ
(3)
ꢀ
ꢀ
m
The most significant contribution to ΔH is expected to be the
hydrogen bonds formed between DAP-Thy pairs, as these are
by far the strongest types of interactions involved in the for-
mation of a DAP-Thy complex. Additional enthalpic contribu-
tions such as dispersion forces or polymer mixing within the
brush may also be possible, but these are expected to play a
much smaller role in dictating the thermodynamics of NCT as-
sembly due to the fact that they are significantly weaker than
the hydrogen bonding interactions (additional discussion in SI).
i
where values of ΔS are the entropy changes associated with the
different polymer linkers being tethered together via DAP-Thy
complexes. As noted above, while there may be additional con-
tributions to this simple approximation, such thermodynamic
parameters are small enough so as to not significantly affect the
conclusions drawn here, and these assumptions should hold for
systems like the NCTs that possess long ligands and directional
2
7,28
enthalpic interactions.
m
The most significant contribution to ΔS is expected to come
Based on these thermodynamic parameters, a “bundle bond”
therefore represents a collection of DAP and Thy groups where
the entropy penalty for linking any given pair of polymer chains
comprising that bundle is less than the strength of the DAP-Thy
complex that is formed. In other words, if a polymer chain has
from the reduction in polymer configurations upon forming a
DAP-Thy complex that restricts the motion of the two adjoined
polymer chains.
The value of ΔH
s
for each DAP-Thy complex within a bundle
bond can be assumed to be constant based on prior evidence in
to stretch so much to become a part of a bundle that the TΔS
i
is
1
9
simpler molecular systems. Thus, ΔH
m s
should be ΔH multi-
greater than ΔH
s
, that polymer will not be a part of that multi-
plied by the number of DAP-Thy complexes that comprise a
valent bundle.
ACS Paragon Plus Environment

Page 5 of 10
1
Journal of the American Chemical Society
This interplay between enthalpy and entropy explains why bun-
also show a corresponding decrease in N, NCTs with smaller
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
dles of DAP and Thy groups only emerge within an NCT-NCT
bond, as the enthalpy benefit of generating a supramolecular
complex is necessary to offset the entropic penalty of restricting
polymer motion; the reduced chemical potential of clustering
the polar head groups is not enough on its own to drive this be-
havior. Additionally, it indicates that changes to NCT structure
at the nanoscale should affect multivalency by altering the ex-
tent to which polymer chain conformations are restricted upon
formation of a bundle bond. Therefore, because the design of
NCTs can be easily varied, a series of well controlled experi-
ments can provide further support of the bundle bond hypothe-
sis, and provide insights into the relationship between nanoscale
structure and multivalency.
particle diameters (12 and 16 nm) exhibit values of N that in-
stead increase with increasing polymer length.
These data indicate that the number of DAP-Thy complexes that
comprise a bundle bond is actually increasing, which can be ex-
plained as a function of polymer packing density. Short poly-
mers grafted onto particles form a dense concentrated brush, but
longer polymers extend further off of the particle surface into
30,31
a semidilute brush regime.
The transition from the concen-
trated to semidilute regimes is dependent on the degree of par-
ticle curvature, with larger spheres requiring longer polymer
lengths to become semidilute. Polymer chain ends in this semi-
dilute regime can occupy a greater number of conformations,
which in turn allows a greater number of DAP groups to bind
to complementary Thy groups on adjacent particles (Fig. 3a).
However, this would also mean that, when comparing two NCT
systems with the same bundle bond size, smaller particle cores
would require greater amounts of polymer chain confinement in
order to form the bundles. These opposing thermodynamic ef-
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
For example, changing the nanoscale shape of an NCT by mod-
ifying particle core diameter is observed to increase the temper-
ature at which NCT-NCT bonds break, as well as values of N
m
and ΔH . The thermodynamics of NCTs were studied by mon-
itoring the dissociation of particles with UV-Vis spectroscopy,
and the resulting thermal transition was fit to the Van’t Hoff
equation to extrapolate relevant thermodynamics values (see
m
fects explain the contrasting trends in ΔH as a function of pol-
ymer length on small and large nanoparticle cores. The greater
surface curvature of the small cores inherently allows for more
polymer flexibility and enables the formation of larger bundle
2
9
supporting information, Figs S6, S7, S20 for further details).
The increase in T and ΔH with increasing nanoparticle core
m
m
diameter can be explained as a function of changes to particle
nanoscale curvature. When two curved surfaces approach one
another, different sets of points on the opposing surfaces are not
necessarily equidistant. Additionally, the polymer chains ex-
tending perpendicularly from the curved surface are not all ini-
tially aligned in the same direction as the NCT-NCT bond (Fig.
3a, left). As a result, polymer chains further from the NCT-NCT
bond axis need to stretch in order to form a DAP-Thy complex,
while polymers directly at the center of the bond will likely
compress in order to allow more polymer chain ends to reach
one another and form supramolecular complexes (Fig. 3a,
right).The more curved the particle surface, the greater the var-
iation in compression and stretching as a function of where the
bonds with increasing polymer length (increasing ΔH
m
and N),
but also requires greater polymer deformation to form these
bundles (larger values of ΔS
despite the larger N).
i m
, which results in a decreased T
In order to further show that the multivalent behavior observed
in NCTs is an effect of nanostructure-induced bundle bonds and
not just an increased local concentration of DAP and Thy
groups at the particle surface, NCTs were co-loaded with con-
trolled ratios of “active” polymers terminating in a supramolec-
ular binding group and “inert” polymers without any such func-
tionality (Fig. S9-S10). In conventional model systems that ex-
plain multivalency solely due to increased local concentration
of binding groups, reducing the number of active chains would
be predicted to lower the degree of multivalency. However, in
i
polymers are grafted to the surface. The values of ΔS resulting
from tethering polymer chains via a supramolecular complex
would therefore be expected to vary more as a function of lateral
distance between binders when NCT particle cores have more
curved surfaces. As a result, lowering particle curvature by in-
creasing particle diameter enables a larger number of polymer
m
the NCT system, the values of N and ΔH did not exhibit any
significant change as a function of density of DAP and Thy
groups (Fig. 4a, Figure S10). These unexpected results imply
that, above a critical fraction of active polymer chains, the local
bonding structure of an NCT-NCT connection must be con-
stant, meaning that the size and the shapes of the bundle bonds
do not change as a function of the number of “active” polymers
within the range studied. The lower melting temperatures for
the coloaded samples must therefore arise from a greater poly-
mer entropy penalty for NCT bonding, as greater deformation
would be required to maintain a constant multivalency. The im-
portance of this finding is to reiterate the initial discovery that
the act of forming a nanoscale bond results in an emergent struc-
ture (the bundle bond), where this new structural motif is the
determinant factor of the entire system’s multivalency. The data
and simulations presented above therefore indicate that the de-
gree of multivalency in an NCT-NCT bond is indeed a complex
interplay of building block structure across length scales, and
that nanoscale structure can be used to modulate bundle bond
behavior.
chains to bundle together and act multivalently. In other words,
ꢁ
ꢀ
the value of N at which ∑ ꢃꢄ overcomes ΔH
m
is higher for
ꢀ
larger diameter cores. This larger value of N correlates to larger
bundle bonds and (based on equation 3) explains the fact that
values of ΔH
totically approaching the limit corresponding to a flat surface
Fig. 3b).
m m
and T increase with particle core size, asymp-
(
Increasing the height of the polymer brush can also use na-
noscale geometric influence to modify NCT bonding thermo-
dynamics, but would be expected to have more complex effects
on multivalency and bundle bond formation. As polymer length
increases, the number of conformations (and thus entropy) of
each polymer chain should also increase. This means that teth-
ering two longer polymer chains together should result in a
larger entropy penalty, indicating that the value of N at which
ΣTΔS
i
exceeds ΔH
m
should decrease, resulting in lower T
m
. Ex-
Nevertheless, because each bundle bond still consists of multi-
ple individual supramolecular complexes, it is also important to
consider the effects of altering the molecular composition of the
system. While this can be achieved via chemical alterations to
periments demonstrate that T
m
does indeed decrease with in-
creasing polymer length for all systems studied (Fig. 3c). How-
ever, while NCTs with larger particle diameters (26, 36, 50 nm)
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 10
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 DAP or Thy complexes (as has been examined in previous
molecular models ), it is also possible to modify the overall
32
structure and chemical behavior of an NCT via alterations to the
solvent environment. Individual hydrogen bonding interactions
typically weaken in more polar solvents, which would be ex-
3
3
s
pected to reduce the value of ΔH . However, the chemical po-
tential between DAP and Thy groups and their local environ-
ment would also decrease when increasing solvent polarity, re-
ducing the driving force for forming the bundles, which could
2
4
lead to larger bundle bonds and greater multivalency.
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
Variable temperature NMR experiments performed on small
molecule DAP and Thy analogues demonstrate that adding a
more polar solvent (1,1,2,2-tetrachloroethane, TCE) does in-
deed decrease ΔH
s
for individual DAP-Thy complexes. This
enthalpy change reaches a minimum value at ~20% TCE, due
34,35
to preferential solvation
complex (Fig. S18-19). However, although ΔH
increasing solvent polarity, the collective ΔH of an NCT bond
actually increases when TCE is added (Fig. 4b). Because each
individual hydrogen bond is weaker, the increase in ΔH indi-
of the moderately polar DAP-Thy
s
decreases with
m
m
cates that N must dramatically increase in the more polar sol-
vent: bundles in the more polar solvents exhibit multivalencies
up to ~250% of their value in pure toluene (N = 10 in toluene
but 25 in 20% TCE for the system in fig. 4b). Simulations con-
firm that adding TCE increases both average bundle bond size
and the rate at which DAP-Thy complexes exchange between
adjacent bundles (Fig. S16-S17). This enhanced mobility af-
fords each supramolecular group a greater number of counter-
parts on a neighboring particle with which it can complex, en-
hancing NCT multivalency (Figs. 4c, 4d). Thus, although each
individual hydrogen bond weakens with increased solvent po-
larity, the increased multivalency results in higher collective
binding strength between NCTs. As a result, the hierarchical or-
dering of an NCT-NCT bond is dictated (and can be controlled)
by a complex and integrated set of design variables across mul-
tiple size regimes. Alterations to molecular composition of the
solvent change the enthalpic driving force for bundle bond for-
mation, while alterations to NCT nanoscale structure alter its
associated entropic penalty. NCTs therefore represent a multi-
valent supramolecular system that, just like natural systems, can
only be regulated and understood by considering material struc-
ture at the molecular and nanoscale simultaneously.
Importantly, the fundamental understanding of NCT bond be-
havior from the experiments above potentially allows for the
development of new design principles for systems-level control
of assembly as a function of these integrated molecular and na-
noscale handles. Prior work has shown that NCTs with symmet-
ric particle sizes and polymer lengths form ordered, crystalline
Figure 4. NCTs exhibit a maximum multivalency, implying satu-
rated bonding behavior. (a) Decreasing the fraction of polymer
chains that have a supramolecular binding group decreases NCT
Tm, but with no significant change in ΔHm. (b) The bundling ef-
fect is hypothesized to originate from the polar supramolecular
binding groups phase segregating from the nonpolar toluene sol-
vent. Introducing a polar solvent (1,1,2,2 tetrachloroethane, TCE)
weakens individual supramolecular bonds (black data, dotted line
represents the DAP-Thy binding strength in 100% TCE), but sur-
prisingly increases the binding enthalpy for the collective NCT-
NCT interaction (blue data). (c) Molecular dynamics simulations
show that increasing solvent polarity decreases the restrictive ef-
fect on the supramolecular binding groups. This can be quantified
by measuring the mean square displacement (MSD) of the binding
groups, which is shown to increase with increasing TCE. (d) Posi-
tions of supramolecular groups at a modeled NCT-NCT interface
show smaller, less multivalent bundles in low polarity solvent
1
6
CsCl-type lattices upon thermal annealing. A crystalline lat-
tice is hypothesized to be the thermodynamically favored state
because it maximizes the number of NCT bonds that can form
and minimizes the entropic penalty associated with polymer
confinement upon binding. This implies that manipulating the
overall morphology of the “bundled” bonds could allow new
phases to be achieved, as these enthalpic and entropic factors
that determine which crystal phase is thermodynamically pre-
ferred are inherently linked to the sizes and shapes of the bun-
dles. As a result, alterations to nanoscale NCT architecture
could be used to regulate both the thermodynamics of supramo-
lecular complex formation and the mesoscale coordination en-
vironment of particles within a lattice.
(
(
blue), and larger, more diffuse bundles in higher polarity solvent
red).
ACS Paragon Plus Environment

Page 7 of 10
1
Journal of the American Chemical Society
For example, an asymmetric NCT system consisting of comple-
zation would also control the amount of nanoscale polymer re-
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
mentary large (20 nm diameter core and 12 kDa polymer) and
small (12.5 nm core and 7 kDa polymer) NCTs was found to
assemble into a lattice isostructural with Th P after thermal an-
3 4
organization needed to maintain the lattice, thereby affecting
the supramolecular bundle sizes and thus collective molecular
thermodynamics—a true “systems” approach to material design
(Figure 1).
nealing. The formation of this lattice symmetry is surprising,
since it has a lower nanoparticle valency and thus fewer in-
terparticle connections than CsCl-type lattices. It has been pos-
Adding TCE to NCT solutions during thermal annealing does
indeed favor the formation of the 4% denser CsCl lattice (Fig.
5), demonstrating that a single set of NCT building blocks can
be driven down two different assembly pathways using solely
changes to solvent composition. The significance of this result
is that the hierarchical ordering in this system cannot be prede-
termined by simply summing up the interactions of individual
molecular binding groups, or considering the larger lattices and
NCT bonds to be just a consequence of the behavior of individ-
ual molecules. Rather, these structures are indeed an example
of a systems-level design process, where the morphology at
each length scale (molecular, nano, and meso) is both an effect
and a cause of behavior at the others.
3
6,37
tulated in other nanoparticle assembly methods
that the
Th phase is favored over CsCl because it alleviates strain in
3
P
4
linkers that are sterically limited in their mobility. This strain
on the ligands induced by assembly also connects to the previ-
ously described bundling behavior, as increasing polymer strain
correlates negatively with the amount of multivalency. In tolu-
ene, the strong driving force for segregation of the DAP and
Thy groups drives the formation of small bundles (N ~10 as
shown above), which restrict the motion of the supramolecular
binding groups. Increasing the solvent polarity would be ex-
pected to increase molecular bond mobility and soften na-
noscale polymer coronae, expanding the size of the supramo-
lecular bundle bonds and increasing the multivalency of the
NCT. In more polar solvents, the higher enthalpic driving force
from the collective supramolecular interaction should be able to
overcome the entropy penalty of straining the polymers, and fa-
vor an alternate superlattice structure. To clarify, the collective
supramolecular interaction of multiple molecular binding
groups arranged around a nanoscale scaffold would result in a
mesoscale superlattice architecture, but this mesoscale organi-
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
It is important to again note that this system-derived change in
NCT coordination environment is different than prior particle
2
3,25,38
assembly schemes that use "patchy" particles
. These
methods typically control particle coordination numbers by
breaking the overall symmetry of the ligand shell around a par-
ticle. Here, the overall ligand shell surrounding the particles re-
mains largely isotropic at the nanoscale, as each NCT-NCT
bond consists of multiple emergent bundle bonds that are
smaller than the length scale of the collective NCT-NCT inter-
actions. Instead of altering the nanoscale symmetry of the par-
ticle building blocks, these bundles regulate the degree of mul-
tivalency to dictate the equilibrium lattice symmetry. The for-
mation of these two unique superlattices and the ability to drive
a single set of NCT building blocks to either crystallographic
symmetry therefore demonstrates the potential for materials de-
sign using a combination of integrated handles across multiple
size regimes.
Conclusion
In order to fully mimic the complexity of naturally occurring
materials made via directed assembly, it is imperative to under-
stand how the interactions between design features at multiple
length scales dictate material structure. The systems-level de-
sign methodology presented here represents a unique platform
for exploring the thermodynamics of multivalent behavior in a
manner that is more similar to a natural system than a simple
molecular model. While this work focuses on the first steps of
controlling material structure and molecular assembly in a sys-
tems-level approach, the modularity of the NCT design poten-
tially allows future exploration of different design handles (e.g.
polymer compositions, supramolecular binding group struc-
tures, particle shapes) to further imitate and explore many dif-
ferent types of multivalent natural systems that use nanoscale
structure to modulate their behavior and hierarchical ordering
across multiple length scales. The understanding gained from
the experiments performed here and these future investigations
is critical for multiple fields where materials require sophisti-
cated structures and interactions between features at the molec-
ular, nano-, and macroscopic length scales, including catalysis,
interface science, and biomimetics. Studying the interplay be-
tween molecular makeup and nanoscale spatial organization
therefore presents a powerful opportunity for programming hi-
erarchical ordering and material behavior beyond the limita-
tions of current reductionist design approaches.
Figure 5. Solvent composition manipulates NCT superlattice crys-
tal structure. (a) Schematic diagram showing the unit cell of a
Th P -type NCT superlattice and 8 unit cells of CsCl-Type lattices,
3 4
which occupy a similar volume. (b) Small angle x-ray scattering
measurements of NCT superlattices in toluene with 0 to 10 volume
percent 1,1,2,2 tetrachloroethane (TCE) as a cosolvent. The top
and bottom dashed patterns are simulated. Increasing TCE modu-
lates the bundle bond size, which then alters the resulting
mesoscale structure of the NCTs.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 8 of 10
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
(
6)
laRica, R. de; Fratila, R. M.; Szarpak, A.; Huskens, J.;
ASSOCIATED CONTENT
Supporting Information
Velders, A. H. Multivalent Nanoparticle Networks as Ultrasensitive
Enzyme Sensors. Angew. Chem. Int. Ed. 2011, 50 (25), 5704–5707.
https://doi.org/10.1002/anie.201008189.
Materials and Methods
Scheme S1 and S2
Figures S1-S20
Tables S1-S8
Supplementary References 1-15
NMR Spectra
(
7)
Prasad Thelu, H. V.; K. Albert, S.; Golla, M.; Krishnan, N.;
Ram, D.; Murty Srinivasula, S.; Varghese, R. Size Controllable DNA
Nanogels from the Self-Assembly of DNA Nanostructures through
Multivalent Host–Guest Interactions. Nanoscale 2018, 10 (1), 222–
2
30. https://doi.org/10.1039/C7NR06985E.
8) Fu, J.-H.; Lee, Y.-H.; He, Y.-J.; Chan, Y.-T. Facile Self-As-
(
sembly of Metallo-Supramolecular Ring-in-Ring and Spiderweb Struc-
tures Using Multivalent Terpyridine Ligands. Angew. Chem. Int. Ed.
2015, 54 (21), 6231–6235. https://doi.org/10.1002/anie.201501507.
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
AUTHOR INFORMATION
Corresponding Author
(
9)
Vial, S.; Nykypanchuk, D.; Yager, K. G.; Tkachenko, A. V.;
*
Correspondence to: rmacfarl@mit.edu.
Present Addresses
Present address: Department of Chemistry and Chemical
Gang, O. Linear Mesostructures in DNA–Nanorod Self-Assembly.
ACS Nano 2013, 7 (6), 5437–5445. https://doi.org/10.1021/nn401413b.
(
10) Deyev, S. M.; Lebedenko, E. N. Multivalency: The Hall-
mark of Antibodies Used for Optimization of Tumor Targeting by De-
sign. BioEssays 2008, 30 (9), 904–918.
https://doi.org/10.1002/bies.20805.
11) Gouin, S. G. Multivalent Inhibitors for Carbohydrate-Pro-
cessing Enzymes: Beyond the “Lock-and-Key” Concept. Chem. – Eur.
J. 2014, 20 (37), 11616–11628.
https://doi.org/10.1002/chem.201402537.
12) Pieters, R. J. Intervention with Bacterial Adhesion by Mul-
†
Biology, Rutgers, the State University of New Jersey, 123
Bevier Rd, Piscataway, New Jersey 08854, United States.
(
Author Contributions
The manuscript was written through contributions of all authors.
All authors have given approval to the final version of the manu-
script.
(
tivalent Carbohydrates. Med. Res. Rev. 2007, 27 (6), 796–816.
https://doi.org/10.1002/med.20089.
(
Kučanda, K.; Manna, D.; Kundu, P. K.; Lee, J.-W.; Král, P.; Klajn, R.
Reversible Trapping and Reaction Acceleration within Dynamically
Self-Assembling Nanoflasks. Nat. Nanotechnol. 2016, 11 (1), 82–88.
https://doi.org/10.1038/nnano.2015.256.
(14) Jones, M. R.; Macfarlane, R. J.; Prigodich, A. E.; Patel, P.
C.; Mirkin, C. A. Nanoparticle Shape Anisotropy Dictates the Collec-
tive Behavior of Surface-Bound Ligands. J. Am. Chem. Soc. 2011, 133
Funding Sources
13) Zhao, H.; Sen, S.; Udayabhaskararao, T.; Sawczyk, M.;
This material is based upon work supported in part by the U. S.
Army Research Office under grant number W911NF-18-1-0197.
This work was primarily supported by an NSF CAREER Grant,
award number CHE-1653289 and made use of the MRSEC
Shared Experimental Facilities at MIT, supported by the NSF un-
der Award DMR 14-19807. P.J.S. acknowledges support by the
NSF Graduate Research Fellowship Program under Grant
1122374. A.A.-K. acknowledges financial support from the De-
partment of Energy BES award # ER46919 for performing the
simulation work.
(
46), 18865–18869. https://doi.org/10.1021/ja206777k.
15) Walker, D. A.; Leitsch, E. K.; Nap, R. J.; Szleifer, I.; Grzyb-
(
owski, B. A. Geometric Curvature Controls the Chemical Patchiness
and Self-Assembly of Nanoparticles. Nat. Nanotechnol. 2013, 8 (9),
676–681. https://doi.org/10.1038/nnano.2013.158.
ACKNOWLEDGMENT
Special thanks to Dr. Byeongdu Lee for helpful discussions.
(
16) Zhang, J.; Santos, P. J.; Gabrys, P. A.; Lee, S.; Liu, C.;
Macfarlane, R. J. Self-Assembling Nanocomposite Tectons. J. Am.
Chem. Soc. 2016, 138 (50), 16228–16231.
https://doi.org/10.1021/jacs.6b11052.
REFERENCES
(17) Simundza, G.; Sakore, T. D.; Sobell, H. M. Base-Pairing
Configurations between Purines and Pyrimidines in the Solid State: V.
Crystal and Molecular Structure of Two 1:1 Hydrogen-Bonded Com-
plexes, 1-Methyluracil: 9-Ethyl-8-Bromo-2,6-Diaminopurine and 1-
Ethylthymine: 9-Ethyl-8-Bromo-2,6-Diaminopurine. J. Mol. Biol.
(
1)
Badjić, J. D.; Nelson, A.; Cantrill, S. J.; Turnbull, W. B.;
Stoddart, J. F. Multivalency and Cooperativity in Supramolecular
Chemistry. Acc. Chem. Res. 2005, 38 (9), 723–732.
https://doi.org/10.1021/ar040223k.
(
2)
Kuna, J. J.; Voïtchovsky, K.; Singh, C.; Jiang, H.;
1
970, 48 (2), 263–278. https://doi.org/10.1016/0022-2836(70)90160-9.
(18) Lehn, J.-M. Supramolecular Chemistry — Molecular Infor-
Mwenifumbo, S.; Ghorai, P. K.; Stevens, M. M.; Glotzer, S. C.; Stel-
lacci, F. The Effect of Nanometre-Scale Structure on Interfacial En-
mation and the Design of Supramolecular Materials. Makromol. Chem.
Macromol. Symp. 1993, 69 (1), 1–17.
https://doi.org/10.1002/masy.19930690103.
19) Mammen, M.; Choi, S.-K.; Whitesides, G. M. Polyvalent In-
ergy.
https://doi.org/10.1038/nmat2534.
3) Huang, M.; Hsu, C.-H.; Wang, J.; Mei, S.; Dong, X.; Li, Y.;
Nat.
Mater.
2009,
8
(10),
837–842.
(
(
Li, M.; Liu, H.; Zhang, W.; Aida, T.; et al. Selective Assemblies of
Giant Tetrahedra via Precisely Controlled Positional Interactions. Sci-
ence 2015, 348 (6233), 424–428. https://doi.org/10.1126/sci-
ence.aaa2421.
teractions in Biological Systems: Implications for Design and Use of
Multivalent Ligands and Inhibitors. Angew. Chem. Int. Ed. 1998, 37
(
3
20),
773(19981102)37:20<2754::AID-ANIE2754>3.0.CO;2-3.
20) Huskens, J.; Mulder, A.; Auletta, T.; Nijhuis, C. A.; Ludden,
2754–2794.
https://doi.org/10.1002/(SICI)1521-
(
4)
Xia, Y.; Nguyen, T. D.; Yang, M.; Lee, B.; Santos, A.; Pod-
(
siadlo, P.; Tang, Z.; Glotzer, S. C.; Kotov, N. A. Self-Assembly of Self-
Limiting Monodisperse Supraparticles from Polydisperse Nanoparti-
M. J. W.; Reinhoudt, D. N. A Model for Describing the Thermodynam-
ics of Multivalent Host−Guest Interactions at Interfaces. J. Am. Chem.
Soc. 2004, 126 (21), 6784–6797. https://doi.org/10.1021/ja049085k.
cles.
https://doi.org/10.1038/nnano.2011.121.
(5) Jishkariani, D.; Diroll, B. T.; Cargnello, M.; Klein, D. R.;
Nat.
Nanotechnol.
2011,
6
(9),
580.
(
21) Guo, P.; Sknepnek, R.; Olvera de la Cruz, M. Electrostatic-
Driven Ridge Formation on Nanoparticles Coated with Charged End-
Group Ligands. J. Phys. Chem. C 2011, 115 (14), 6484–6490.
https://doi.org/10.1021/jp201598k.
Hough, L. A.; Murray, C. B.; Donnio, B. Dendron-Mediated Engineer-
ing of Interparticle Separation and Self-Assembly in Dendronized Gold
Nanoparticles Superlattices. J. Am. Chem. Soc. 2015, 137 (33), 10728–
(
22) Donakowski, M. D.; Godbe, J. M.; Sknepnek, R.; Knowles,
1
0734. https://doi.org/10.1021/jacs.5b06306.
K. E.; Olvera de la Cruz, M.; Weiss, E. A. A Quantitative Description
ACS Paragon Plus Environment

Page 9 of 10
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
of the Binding Equilibria of Para-Substituted Aniline Ligands and
CdSe Quantum Dots. J. Phys. Chem. C 2010, 114 (51), 22526–22534.
https://doi.org/10.1021/jp109381r.
(32) Beijer, F. H.; Sijbesma, R. P.; Vekemans, J. A. J. M.; Meijer,
E. W.; Kooijman, H.; Spek, A. L. Hydrogen-Bonded Complexes of Di-
aminopyridines and Diaminotriazines:ꢀ Opposite Effect of Acylation on
Complex Stabilities. J. Org. Chem. 1996, 61 (18), 6371–6380.
https://doi.org/10.1021/jo960612v.
(33) Li, C.-P.; Du, M. Role of Solvents in Coordination Supra-
molecular Systems. Chem. Commun. 2011, 47 (21), 5958–5972.
https://doi.org/10.1039/C1CC10935A.
(34) Amenta, V.; Cook, J. L.; Hunter, C. A.; Low, C. M. R.;
Vinter, J. G. Influence of Solvent Polarity on Preferential Solvation of
Molecular Recognition Probes in Solvent Mixtures. J. Phys. Chem. B
2012, 116 (49), 14433–14440. https://doi.org/10.1021/jp310379h.
(35) Bagno, A.; Campulla, M.; Pirana, M.; Scorrano, G.; Stiz, S.
Preferential Solvation of Organic Species in Binary Solvent Mixtures
Probed by Intermolecular 1H NOESY NMR Spectroscopy. Chem. –
Eur. J. 1999, 5 (4), 1291–1300. https://doi.org/10.1002/(SICI)1521-
3765(19990401)5:4<1291::AID-CHEM1291>3.0.CO;2-M.
(36) Thaner, R. V.; Eryazici, I.; Macfarlane, R. J.; Brown, K. A.;
Lee, B.; Nguyen, S. T.; Mirkin, C. A. The Significance of Multivalent
Bonding Motifs and “Bond Order” in DNA-Directed Nanoparticle
Crystallization. J. Am. Chem. Soc. 2016, 138 (19), 6119–6122.
https://doi.org/10.1021/jacs.6b02479.
(
23) Choueiri, R. M.; Galati, E.; Thérien-Aubin, H.; Klinkova,
A.; Larin, E. M.; Querejeta-Fernández, A.; Han, L.; Xin, H. L.; Gang,
O.; Zhulina, E. B.; et al. Surface Patterning of Nanoparticles with Pol-
ymer
https://doi.org/10.1038/nature19089.
24) Narumi, A.; Miura, Y.; Otsuka, I.; Yamane, S.; Kitajyo, Y.;
Patches.
Nature
2016,
538
(7623),
79–83.
(
Satoh, T.; Hirao, A.; Kaneko, N.; Kaga, H.; Kakuchi, T. End-Function-
alization of Polystyrene by Malto-Oligosaccharide Generating Aggre-
gation-Tunable Polymeric Reverse Micelle. J. Polym. Sci. Part Polym.
Chem. 2006, 44 (16), 4864–4879. https://doi.org/10.1002/pola.21582.
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
(
25) Zhang, Z.; Glotzer, S. C. Self-Assembly of Patchy Particles.
Nano Lett. 2004, 4 (8), 1407–1413. https://doi.org/10.1021/nl0493500.
26) Travesset, A. Soft Skyrmions, Spontaneous Valence and Se-
(
lection Rules in Nanoparticle Superlattices. ACS Nano 2017, 11 (6),
5375–5382. https://doi.org/10.1021/acsnano.7b02219.
(27) Batista, C. A. S.; Larson, R. G.; Kotov, N. A. Nonadditivity
of Nanoparticle Interactions. Science 2015, 350 (6257), 1242477.
https://doi.org/10.1126/science.1242477.
(
28) Liepold, C.; Smith, A.; Lin, B.; de Pablo, J.; Rice, S. A. Pair
and Many-Body Interactions between Ligated Au Nanoparticles. J.
Chem. Phys. 2019, 150 (4), 044904.
https://doi.org/10.1063/1.5064545.
29) Jin, R.; Wu, G.; Li, Z.; Mirkin, C. A.; Schatz, G. C. What
(37) Wang, M. X.; Brodin, J. D.; Millan, J. A.; Seo, S. E.; Girard,
M.; Olvera de la Cruz, M.; Lee, B.; Mirkin, C. A. Altering DNA-
Programmable Colloidal Crystallization Paths by Modulating Particle
(
Repulsion.
Nano
Lett.
2017,
17
(8),
5126–5132.
Controls the Melting Properties of DNA-Linked Gold Nanoparticle As-
semblies? J. Am. Chem. Soc. 2003, 125 (6), 1643–1654.
https://doi.org/10.1021/ja021096v.
(30) Choi, J.; Dong, H.; Matyjaszewski, K.; Bockstaller, M. R.
Flexible Particle Array Structures by Controlling Polymer Graft Archi-
tecture. J. Am. Chem. Soc. 2010, 132 (36), 12537–12539.
https://doi.org/10.1021/ja105189s.
https://doi.org/10.1021/acs.nanolett.7b02502.
(38) Zhu, H.; Fan, Z.; Yu, L.; Wilson, M. A.; Nagaoka, Y.; Eg-
gert, D.; Cao, C.; Liu, Y.; Wei, Z.; Wang, X.; et al. Controlling Nano-
particle Orientations in the Self-Assembly of Patchy Quantum Dot-
Gold Heterostructural Nanocrystals. J. Am. Chem. Soc. 2019.
https://doi.org/10.1021/jacs.9b01033.
(
31) Milner, S. T.; Witten, T. A.; Cates, M. E. Theory of the
Grafted Polymer Brush. Macromolecules 1988, 21 (8), 2610–2619.
https://doi.org/10.1021/ma00186a051.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 10 of 10
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
Insert Table of Contents artwork here
ACS Paragon Plus Environment