Hydrogen-Bonding-Regulated Supramolecular Nanostructures and Impact on Multivalent Binding

Article abstract of DOI:10.1002/anie.201812217

Herein we describe the H-bonding-regulated nanostructure, thermodynamics, and multivalent binding of two bolaamphiphiles NDI-1 and NDI-2 consisting of a hydrophobic naphthalene diimide connected to a hydrophilic wedge by a H-bonding group and a glucose mo

Full text of DOI:10.1002/anie.201812217

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Hydrogen Bonding Regulated Supramolecular Nanostructures
and Impact on Multivalent Binding
Authors: Suhrit Ghosh, Amrita Sikder, Debes Ray, and Vinod K Aswal
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201812217
Angew. Chem. 10.1002/ange.201812217
Link to VoR: http://dx.doi.org/10.1002/anie.201812217
http://dx.doi.org/10.1002/ange.201812217

10.1002/anie.201812217
Angewandte Chemie International Edition
COMMUNICATION
Hydrogen Bonding Regulated Supramolecular Nanostructures
and Impact on Multivalent Binding
Amrita Sikder[a], Debes Ray[b], Vinod K Aswal, [b] and Suhrit Ghosh*[a]
Abstract: This communication reveals H-bonding regulated
functional group display and multivalent binding with biological
targets, we have studied a few new NDI-derived unsymmetric
bola-amphiphiles (Scheme 1). NDI-1 and NDI-2 differ merely by
the H-bonding group, hydrazide and amide, respectively, while
NDI-3 lacks any H-bonding functionality. All of them contain a
glucose so that the impact of the supramolecular assembly on
multivalent binding can be studied using Lectin as the model
biological target. [11] This communication reveals the remarkable
impact of a marginal structural difference in the unimer on the
morphology, thermodynamics and multivalent binding ability of
the resulting nanostructures.
nanostructure, thermodynamics and multivalent binding of two bola-
amphiphiles (NDI-1, NDI-2) consisting of
a
hydrophobic
naphthalene-diimide (NDI), connected to a hydrophilic wedge by a
H-bonding group and a glucose moiety on its two arms. They differ
by the single H-bonding group, namely hydrazide and amide, which
triggers formation of vesicle and cylindrical micelle, respectively. H-
bonding among the rigid hydrazides in NDI-1 contributes to a major
enthalpy gain and relatively less entropy gain. For NDI-2, a relatively
less enthalpy gain is compensated by the additional entropy
originated from the conformational freedom of the open structure.
Although the extended H-bonding ensures stacking with head-to-
head orientation and multiple array of the appended glucose
moieties in both systems, adaptive cylindrical structure exhibits
superior multivalent binding with Concanavalin (ConA) than that of
the vesicle. Control amphiphile (NDI-3), lacking any H-bonding group,
assembles with random lateral orientation, producing spherical
micelle without any notable multivalent binding.
Aggregation of amphiphilic molecules [1] and macromolecules [2]
produce wide ranging nanostructures depending on the structure
of the unimer. Surface functional group display in these
Scheme 1. Structure of various NDI-amphiphiles
[3]
nanostructures endows multivalent binding with cell surface,[4]
Dynamic light scattering (DLS) of NDI-1 showed a sharp peak
with average Dh of ~160 nm while that for NDI-2 indicated much
larger aggregates (Fig 1a). Transmission electron microscopy
(TEM) images (Fig 1b, S1) showed hollow spherical structures
for NDI-1 with diameter in the range of 150-200 nm
corroborating with the DLS. UV/Vis spectra (Fig S2) of Calcein
treated NDI-1 aggregates revealed 13 % dye loading efficiency
which matches with reported values for vesicles of comparable
size.[12] Absorption normalized florescence intensity of the
entrapped Calcein was found to be significantly less (Fig S2)
compared to that of the free dye in water, which typically has
been attributed to self-quenching of the dye in the water filled
lacuna of vesicles.[13] These observations corroborate with our
previous reports[10] in supporting vesicular assembly of NDI-1. In
sharp contrast, TEM image of NDI-2 (Fig 1c, S1) showed 1D
protein,[5] DNA,[6] heparin[7] and other biological targets which
has important applications. To achieve effective and specific
multivalent binding in the complex biological milieu, it requires
precise engineering of these nanostructures by taking into
consideration of several issues such as stability, morphology,
surface functional group display and density, adaptability and so
on. In this regard, supramolecular polymers of π-systems in
water [8, 9] appear promising owing to their precise internal order,
stability, optical properties and the possibility to fine tune the
structural parameters by directional molecular interaction unlike
the immiscibility driven aggregation of classical amphiphiles. We
[10]
have recently developed
a supramolecular strategy that
enables H-bonding regulated unidirectional assembly of a bola-
shape π-amphiphile (NDI-1a, Scheme 1) and construction of
unsymmetric vesicle. The propensity of the H-bonded chain of
the hydrazides to remain shielded at the inner wall prevailed
over electrostatic and/or steric factors resulting in display of the
anionic groups at the outer surface. To test the scope of this
design for synthesis of precision nanostructures with desired
fibrils with diameter of ~ 25-30 nm and length extending over a
[14-15]
few micrometers.
Differing with both, NDI-3 formed
relatively smaller spherical particles (Fig 1d, S1) with diameter in
the range of 40-60 nm which was consistent with DLS (Fig 1a)
revealing Dh of 50-60 nm. To further elucidate the morphological
differences, small-angle neutron scattering (SANS) experiments
[16]
were performed (Fig 2).
The SANS data from NDI-1 was
[a]
[b]
Ms Amrita Sikder and Professor Dr. Suhrit Ghosh
School of Applied and Interdisciplinary Sciences, Indian Association
for the Cultivation of Science, Kolkata, India-700032
E-mail: psusg2@iacs.res.in
Dr. Debes Ray and Dr. Vinod K Aswal
Solid State Physics Division, Bhabha Atomic Research Centre,
Mumbai-400085
analyzed using a model of unilamellar vesicles (ULV). In the low-
Q region (< 0.05 Å-1), the scattering intensity decreased in a
straight line as 1/Q2 indicating presence of large vesicles. At
higher Q values (> 0.05 Å-1), there was increase in the drop of
the intensity and a minimum was observed, which depends on
the thickness of the hydrophobic component (monolayer). These
ULVs thus were characterized by the monolayer thickness (t) =
12.10.7 Å as the measurement of the radius of the vesicle (Rv)
was limited by the Qmin of the SANS instrument.
E-mail: vkaswal@barc.gov.in
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201812217
Angewandte Chemie International Edition
COMMUNICATION
clustering of the individual fibers in the dry state TEM while
SANS could probe the diameter of the single fiber. On the other
hand, NDI-3 was found to consist of spherical micelles with core
radius (Rc) = 11.80.7 Å and the polydispersity (σ) = 0.220.03.
Thermodynamic parameters associated with aggregation were
estimated (Table 1) from the isothermal titration calorimetry
[17]
(ITC).
Fig 3 shows an ITC dilution experiment of NDI-1
revealing an endothermic heat flow which saturated beyond a
certain concentration. The experiment was repeated for two
more times (Fig S4) while consistent results were obtained. The
initial heat change was assigned to the heat of dissociation while
beyond the saturation only the heat of dilution persisted.
Likewise ITC experiments were performed for NDI-2 and NDI-3
(each in triplicate) which revealed similar trends (Fig S5,
S6).The saturation concentration was considered as the critical
aggregation concentration (CAC) while the difference of heat
between the initial and final state was taken as the enthalpy of
aggregation (H). For NDI-1, concentration dependent UV/Vis
studies (Fig S7) revealed a CAC value of 0.17 mM which
corroborated with the ITC estimated value (Table 1). The free
energy (ΔG) and the entropy (ΔS) of aggregation were
estimated using these ITC data following reported procedure
(see SI for detail). H and CAC varied in the order NDI-1 > NDI-
2 > NDI-3 and NDI-1 < NDI-2 < NDI-3, respectively, which is
attributed to a relatively stronger H-bonding between hydrazides
than amides [15] and lack of H-bonding in NDI-3.
Fig 1. a) Particle size distribution of different aggregates obtained from DLS;
TEM images of nanostructures obtained from aqueous solution of b) NDI-1, c)
NDI-2 and d) NDI-3. C = 1.0 mM. Black spots in b) could be drying artifacts.
Fig 3. a) Heat release per injection of an aqueous solution of NDI-1 in ITC
dilution experiment (C=5.0 mM, T= 25 oC) and b) corresponding enthalpogram.
Fig 2. SANS plot of the scattering intensity as a function of scattering vector Q
for NDI-amphiphiles. The plots for NDI-2 and NDI-3 are vertically shifted for
clarity.
Table 1. Thermodynamic parameters (average values have been reported
from three independent ITC experiments) associated with the aggregation of
various NDI derivatives.
The absence of lower cut-offs in the data indicates that the radii
of the vesicles could be larger than what could be determined
from the present Qmin and therefore the radius of the vesicle was
kept fixed at a higher value than to a value of 2π/Qmin, i.e., ~350
Å. The inaccessibility of the SANS data at low-Q has been
addressed with the use of static light scattering (SLS) technique.
From SLS, using Guinier approximation (Fig S3), the radius of
the vesicles was found to be ~72 nm which is in close
agreement with the hydrodynamic radius Rh (~ 75 nm) obtained
from DLS.The SANS data of NDI-2 was distinctly different and
analyzed using a model of long cylinders. In the low-Q region of
the data, the scattering intensity decreased following a power
law as 1/Q indicating the formation of long cylindrical micelles.
These cylinders were characterized by the cross-sectional
radius (Rcr) = 13.20.8 Å while the measurement of their length
(L) was limited by the Qmin of the instrument. Noteworthy that the
diameter of the fibers was estimated to be 25-30 nm from TEM
image (Fig 2c). The difference can be attributed to the lateral
System
CAC (mM)
H
S
G
(kCalM-1)
(CalM-1K-1)
(kCalM-1)
NDI-1
NDI-2
ND- 3
0.15±0.02
0.29±0.03
0.4±0.05
- 3.9±0.04
-0.65±0.05
-0.4±0.04
4.4±0.1
13.2±0.1
13.9 ±0.3
-5.2±0.04
-4.8±0.05
-4.5±0.07
FT-IR spectra (Fig S8) of NDI-1 in THF showed a distinct peak
at 1702 cm-1 assigned to the CO stretching of the non-bonded
hydrazide which shifted to 1672 cm-1 in D2O and also in bulk
suggesting H-bonding. For NDI-2, the amide carbonyl stretching
peak merged with the imide carbonyl peaks of NDI and thus
quantitative analysis was not possible. However, by comparing
the spectra in THF, D2O and bulk (Fig S9), H-bonding among
the amide groups was evident in D2O. Positive ΔS values
indicated entropically favourable supramolecular assembly in all
This article is protected by copyright. All rights reserved.

10.1002/anie.201812217
Angewandte Chemie International Edition
COMMUNICATION
[18]
[8c, 19]
three systems
and attributed to the hydrophobic effect
gradual addition of NDI-1(C=0.1 mg/mL, λmax= 480 nm); d) Steck- Wallack plot
of fluorescence intensity change in FITC-ConA with NDI-1; e) Relative Ka
values for binding of ConA with various NDI derivatives (Scheme 1 or 2).
due to the release of the surrounding water molecules during
aggregation. Nevertheless, significantly higher ΔS values
estimated for NDI-2 and NDI-3 compared to NDI-1 cannot be
rationalized only by the hydrophobic effect as the π-surface
remains the same in all three systems. Possibly, 1D fibrils of
NDI-2 enjoys more conformational freedom than vesicles of NDI-
1 and therefore the former is entropically more favourable. On
the other hand, lack of any H-bonding induced restriction makes
the NDI-3 aggregates more disordered and dynamic which
contributed to the enhanced entropy. It is noteworthy that by
enthalpy-entropy compensation, the G values appear to be
comparable for all the three systems.
A model to rationalize the observed variations has been
proposed in Scheme 2. Involvement of H-bonding among the
hydrazides in the π-stacked assembly of NDI-1 ensures a fixed
uni-lateral orientation of leading to the formation of unsymmetric
vesicles. Excellent binding efficiency with ConA confirms the
display of the glucose moieties in the outer surface of the vesicle
which is consistent with our earlier report. [10] In our earlier report,
[10] it was shown that the functional group display depends on the
location of the hydrazide group as the direction of the curvature
was determined by the preference of the H-bonded chain to
remain at the inner wall of the vesicle. To verify whether a
similar control exists in the present system, NDI-4 (Scheme 2)
was studied which differs with NDI-1 merely by the location of
the hydrazide group. UV/Vis and DLS experiments (Fig S12)
confirmed aqueous aggregates of NDI-4. However, unlike NDI-1,
in this case no glycocluster effect was noticed (Fig S13). Binding
study with FITC-ConA revealed (Fig S14) negligible change in
the fluorescence intensity indicating lack of multi-valent binding.
Such sharp contrast between NDI-1 and NDI-4 ascertains that
the surface display of the sugar units is regulated solely by the
location of the hydrazide group. To further examine whether all
the glucose moieties in NDI-1 were displayed at the outer wall,
its binding affinity was compared with NDI-5 (Scheme 2), having
sugar moieties in both ends. It also showed signature of
aggregation in water as evident from UV/ Vis and DLS (Fig S15).
In this case Ka was estimated to be 1.7×103 M-1 from
fluorescence studies (Fig S16). The fact that Ka for NDI-1 is
even higher than that of NDI-5 strongly favors the hypothesis on
uni-directional orientation of NDI-1 in vesicular assembly
(Scheme 2). Slightly lower value for NDI-5 may be related to its
restricted mobility due to the presence of two hydrazide groups.
On the other hand, NDI-3, lacking any H-bonding restriction,
stacks with irregular lateral orientation leading to the micellar
structure with random distribution of the oligo-oxyethylene
wedge and the sugar groups on the surface resulting in
negligible glycocluster effect. Lack of accessibility of the ligand
due to crowding might have also inhibited efficient interaction.
Interesting is the comparison between NDI-1 and NDI-2. A mere
difference in the nature of the H-bonding group appears to make
a sea change in the morphology which can be attributed to the
difference in internal order of the molecular assembly in these
two systems which was evident from their UV/Vis spectra (Fig
S17). Firstly, the UV/Vis spectra of all three systems in water
indicated π-stacking. [23] But for NDI-2, the spectrum showed a
more prominent bathochromic shift (6 nm) and a red-shifted
We examined the impact of supramolecular structure on the
binding affinity with a lectin protein ConcanavalinA (ConA) which
specifically
binds
with
α-D-mannosyl
and
α-D-
glucosyl ligands.[11] When aqueous solutions of NDI-1 or NDI-2
were treated with ConA, the mixture instantly became turbid (Fig
4) indicating efficient glycocluster effect. In sharp contrast, a
mixture of ConA and NDI-3 did not produce much turbidy
suggesting lack of efficient binding. Optical density (at 420 nm)
as a function of time showed a sharp rise for both NDI-1 and
NDI-2 up to first 2 minutes after mixing followed by saturation
indicating fast binding. Higher optical density in case of NDI-2
than NDI-1 may suggest enhanced glycoclustering in presence
of the linear supramoleular structure. To estimate the binding
affinities, fluorescence quenching titration was performed using
fluorescein isothiocyanate tagged ConA (FITC-ConA).
Fluorescence intensity of FITC-ConA decreased by ~ 80 % upon
gradual addition of NDI-1 (Fig 4)[20] and from these data Ka was
estimated to be 3.2×103 M-1 using the Steck-Wallack plot [21] (Fig
4d) which is in the similar range with polymeric
nanostructures.[11] In sharp contrast, negligible florescence
change was noticed (Fig S10) for NDI-3 which suggested lack of
any multi-valent binding.[22] When similar experiment was
performed with NDI-2 (Fig S11), the Ka (1.35×104 M-1) was found
to be almost an order of magnitude higher than NDI-1
suggesting cylindrical structure to have even superior impact
than vesicular structure for multivalent binding.
band appeared at 387 nm indicating longitudinal displacement of
[24]
the chromophores
which possibly triggered the formation of
elongated 1D structure. In contrast for NDI-1, the distinct H-
bonding motif of the hydrazide compelled a face to face stacking
and provided the curvature for vesicular structure. Open chain
1D structure of NDI-2 is expected to be more adaptive than NDI-
1 vesicle, rendering better glycocluster effect which requires
adjustment of the conformation of the multi-valent ligand to
simultaneously binds to the four binding centers of the tetrameric
ConA.[11]
Fig 4. a) Variation of absorbance at 420 nm as a result of scattering in the
mixture of Con A and NDI-derivatives (C=1.0 mM); b) Picture of aqueous
dispersions of (i) NDI-1 (ii) NDI-1+ConA (iii) NDI-2 and (iii) and (iv) NDI-
2+ConA (C=1.0 mM); c) Change in fluorescence intensity of FITC ConA with
This article is protected by copyright. All rights reserved.

10.1002/anie.201812217
Angewandte Chemie International Edition
COMMUNICATION
[2]
For reviews on aggregation of amphiphilic polymers see: a) Y. Li, B. S
Lokitz; C. L. McCormick, Angew. Chem. Int. Ed. 2006, 45, 5792; b) T.
S. Kale, A. Klaikherd, B. Popere, S. Thayumanavan, Langmuir 2009,
25; 9660; c) J. Dua, R. K. O’Reilly, Soft Matter 2009, 5, 3544; d) O.
Onaca, R. Enea, D. W. Hughes, W. Meier, Macromol. Biosci. 2009, 9,
129; e) R. P. Brinkhuis, F. P. J. T. Rutjes, J. C. M. van Hest, Polym.
Chem. 2011, 2, 1449; f) Y. Mai, A. Eisenberg, Chem. Soc. Rev. 2012,
41, 5969.
[3]
a) A. Barnard, D. K. Smith, Angew. Chem. Int. Ed. 2012, 52, 6572; b)
C. Fasting, C. A. Schalley, M. Weber, O. Seitz, S. Hecht, B. Koksch, J.
Dernedde, C. Graf, E. W. Knapp, R. Haag, Angew. Chem. Int. Ed. 2012,
51, 10472.
[4]
[5]
T. K. Lindhorst, Top. Curr. Chem. 2002, 218, 201.
a) V. Martos, P. Castreṅo, J. Valero, J. de Mendoza, Curr. Opi. In
Chem. Bio. 2008, 12, 698; b) B. S. Sandanaraj, D. R. Vutukuri, J. M.
Simard, A. Klaikherd, R. Hong, V. M. Rotello, S. Thayumanavan. J. Am.
Chem. Soc. 2005, 127, 10693.
[6]
[7]
[8]
M. A. Kostiainen, J. G. Hardy, D. K. Smith, Angew. Chem. Int. Ed. 2005,
44, 2556.
S. M. Bromfield, E. Wilde, D. K. Smith, Chem. Soc. Rev. 2013, 42,
9184.
a) H-J. Kim, T. Kim, M. Lee, Acc. Chem. Res. 2011, 44, 72; b) S. S.
Babu, V. K. Praveen, A. Ajayaghosh, Chem. Rev. 2014, 114, 1973; c)
M.R. Molla, S. Ghosh, Phys. Chem. Chem. Phys. 2014, 16, 26672; b)
c) E. Krieg, M. M. C Bastings, P. Besenius, B. Rybtchinski, Chem. Rev.
2016, 116, 2414; d) T. Aida, E. W. Meijer, S. I. Stupp, Science 2012,
335, 813
Scheme 2. a) Schematic depiction of various nanostructures produced by
NDI-amphiphiles. While this scheme shows uni-directional orientation and
functional group display and corroborates with the experimental results, in
reality some minor deviation cannot be eliminated; b) Structure of the sugar
containing control NDI-amphiphiles.
[9]
a) L. Brunsveld, H. Zhang, M. Glasbeek, J. A. J. M. Vekemans, E. W.
Meijer, J. Am. Chem. Soc. 2000, 122, 6175; b) X. Zhang, S. Rehm, M.
M. Safont-Sempere, F. Würthner, Nat. Chem. 2009, 1, 623; c) J. P. Hill,
W. Jin, A. Kosaka, T. Fukushima, H. Ichihara, T. Shimomura, K. Ito, T.
Hashizume, N. Ishii, T. Aida, Science 2004, 304, 1481; e) J. F. Hulvat,
M. Sofos, K. Tajima, S. I. Stupp, J. Am. Chem. Soc. 2005, 127, 366; f)
N. K. Allampally, A. Florian, M. J. Mayoral, C. Rest, V. Stepanenko, G.
Fernàndez, Chem. Eur. J. 2014, 20, 10669; g) X. Lin, H. Kurata, D. D.
Prabhu, M. Yamauchi, T. Ohba, S. Yagai, Chem. Commun. 2017, 53,
168; h) M. Kumar, S. J. George, Nanoscale 2011, 3, 2130; i) H. Shao, J.
R. Parquette, Chem. Commun. 2010, 46, 4285; j) M. B. Avinash, E.
Verheggen, C. Schmuck, T. Govindaraju, Angew. Chem. Int. Ed. 2012,
51, 10324; k) S. Ghosh, D. S. Philips, A. Saeki, A. Ajayaghosh, Adv.
Mater. 2017, 29, 1605408; l) J.-H. Ryu, H.-J. Kim, Z. Huang, E. Lee, M.
Lee, Angew. Chem. Int. Ed. 2006, 45, 5304; m) E. Lee, J.-K. Kim, M.
Lee, Angew. Chem. Int. Ed. 2009, 48, 3657; n) G. Na, Y. He, Y. Kim,
M. Lee, Soft Matter, 2016, 12, 2846; o) T. Noguchi, B. Roy, D.
Yoshihara, J. Sakamoto, T. Yamamoto, S. Shinkai, Angew. Chem. Int.
Ed. 2016, 55, 5708.
Overall, we have shown that H-bonding can restrict the lateral
orientation of the unimers in the assembly of unsymmetric π-
amphiphiles and renders an excellent display of ligands. H-
bonding also affects the internal order and thus controls the
morphology, thermodynamics and adaptability of the resulting
nanostructures which strongly impact the multi-valent binding.
[25]
Cylindrical structure
Packing parameter
performs better than spherical vesicles.
dependent morphology variation and the
[26]
effect on the multivalent binding and other events have been
[27]
reported.
However, it requires a substantial structural
modification and mass change. This communication shows the
possibility to achieve the same by a minimal change in the
structure as the self-assembly is governed by directional
molecular interaction, and thus advocates its enormous potential
for precision nanostructures and complex biological function.[28]
[10] a) A. Sikder, A. Das, S. Ghosh, Angew. Chem. Int. Ed. 2015, 54, 6755;
b) A. Sikder, D. Ray, V. K. Aswal, S. Ghosh, Langmuir 2018, 34, 868.
[11] a) J. J. Lundquist, E. J. Toone, Chem. Rev. 2002, 102, 555; b) S. R. S.
Ting, G. Chen, M. H. Stenzel, Polym. Chem. 2010, 1, 1392; c) Y. Miura,
Y. Hoshino, H. Seto, Chem. Rev. 2016, 116, 1673.
[12] N. Berger, A. Sachse, J. Bender, R. Schubert, M. Brandl, Int. J. Pharm.
2001, 223, 55.
Acknowledgements
[13] E. N. Savariar, S. V. Aathimanikandan, S. Thayumanavan, J. Am.
Chem. Soc. 2006, 128, 16224.
AS thanks CSIR, India for a research fellowship. SG thanks DST,
India, for funding through the SwarnaJayanti Fellowship Project
(DST/SJF/CSA-01/2-14-15).
[14] P. Pramanik, D. Ray, V. K. Aswal, S. Ghosh, Angew. Chem. Int. Ed.
2017, 56, 3516.
[15] M. R. Molla, S. Ghosh, Chem. Mater. 2011, 23, 95.
[16] D. I. Svergun, M. H. J. Koch, Rep. Prog. Phys. 2003, 66, 1735
[17] R. Zana, Langmuir 1996, 12, 1208.
Keywords: Supramolecular assembly • H-bonding • Vesicle •
Cylindrical micelle • Multivalent binding
[18] a) J. Kang, J. Rebek, Jr., Nature 1996, 382, 239; b) C. Schmuck,
Tetrahedron 2001, 57, 3063; c) D. Görl, F. Würthner. Angew. Chem. Int.
Ed. 2016, 55, 12094; d) O. Munkhbat, M. Garzoni, K. R. Raghupathi, G.
M. Pavan, S. Thayumanavan, Langmuir 2016, 32, 2874.
[19] W. Blokzijl, J. B. F. N. Engberts, Angew. Chem. Int. Ed. 1993, 32, 1545.
[1]
a) D. F. Evans, H. Wennerstrom, The Colloidal Domain, 2nd ed.; Wiley-
VCH: New York, 1999.
This article is protected by copyright. All rights reserved.

10.1002/anie.201812217
Angewandte Chemie International Edition
COMMUNICATION
[20] a) H. Shi, L. Liu, X. Wang, J. Li, Polym. Chem. 2012, 3, 1182; b) Y.
Miura, T. Ikeda, K. Kobayashi, Biomacromolecules 2003, 4, 410; c) I.
Otsuka, T. Otsuka, H. Nakade, A. Narumi, R. Sakai, T. Satoh, H. Kaga,
T. Kakuchi, Macromolecules 2007, 40, 8930.
[26] J. N. Israelachvili, D. J. Mitchell, B. W. Ninham, J. Chem. Soc., Faraday
Trans. 2 1976, 72, 1525.
[27] a) B.-S. Kim, D.-J Hong, J. Bae, M. Lee, J. Am. Chem. Soc. 2005, 127,
16333; b) J.-H. Ryu, E. Lee, Y.-B. Lim, M. Lee, J. Am. Chem. Soc.
2007, 129, 4808; c) D. J. Welsh, P. Posocco, S. Pric, l D. K. Smith, Org.
Biomol. Chem. 2013, 11, 3177; c) Y. Geng, P. Dalhaimer, S. Cai, R.
Tsai, M. Tewari, T. Minko, D. E. Discher, Nat. Nanotechnol. 2007, 2,
249; d) W. Zhao, H. T. Ta, C. Zhang, A. K. Whittaker,
Biomacromolecules 2017, 18, 1145; e) A. C. Rodrigo, S. M. Bromfield,
E. Laurini, P. Posocco, S. Pricl, D. K. Smith, Chem. Commun. 2017,
53, 6335.
[21] T. Furuike, N. Nishi, S. Tokura, S.-I. Nishimura, Macromolecules 1995,
28, 7241.
[22] F. G. Loontiens, J. P. V. Wauwe, C. K. D. Bruyne, Carbohydr. Res.
1975, 44, 150.
[23] A. Das, S. Ghosh, Chem. Commun. 2016, 52, 6860.
[24] F. Würthner, T. E. Kaiser, C. R. Saha-Möller, Angew. Chem. Int. Ed.
2011, 50, 3376.
[25] a) Y. Geng, P. Dalhaimer, S. Cai, R. Tsai, M. Tewari, T. Minko, D. E.
Discher, Nat. Nanotechnol. 2007, 2, 249; b) X. Wang, G. Guerin, H.
Wang, Y. Wang, I. Manners, M. A. Winnik, Science 2007, 317, 644; c)
N. Petzetakis, A. P. Dove, R. K. O'Reilly, Chem. Sci. 2011, 2, 955.
[28] M. J. Webber, E. A. Appel, E. W. Meijer, R. Langer, Nature Mater. 2016,
15, 13.
This article is protected by copyright. All rights reserved.

10.1002/anie.201812217
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
Text for Table of Contents
Amrita Sikder, Debes Ray, Vinod K
Aswal and Suhrit Ghosh*
Page No. – Page No.
Hydrogen Bonding Regulated
Supramolecular Nanostructures and
Impact on Multivalent Binding
H-bonding regulated lateral orientation and internal order
in
π-stacked
assembly
of
glucose-appended
produces diverse
.
unsymmetric
bola-amphiphiles
nanostructures with distinct functional group display
which makes a strong impact on the multivalent binding
efficacy with a biological target.
This article is protected by copyright. All rights reserved.