Solvent clathrate driven dynamic stereomutation of a supramolecular polymer with molecular pockets

Article abstract of DOI:10.1021/jacs.7b07639

Control over the helical organization of synthetic supramolecular systems is intensively pursued to manifest chirality in a wide range of applications ranging from electron spin filters to artificial enzymes. Typically, switching the helicity of supramole

Full text of DOI:10.1021/jacs.7b07639

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Article
Solvent Clathrate Driven Dynamic Stereomutation of
a Supramolecular Polymer with Molecular Pockets
Chidambar Kulkarni, Peter A. Korevaar, Karteek K. Bejagam,
Anja R.A. Palmans, E. W. Meijer, and Subi J. George
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b07639 • Publication Date (Web): 11 Sep 2017
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Solvent Clathrate Driven Dynamic Stereomutation of a
Supramolecular Polymer with Molecular Pockets
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Chidambar Kulkarni,a,c Peter A. Korevaar,a Karteek K. Bejagam,b Anja R. A. Palmans,a
E. W. Meijer,*,a and Subi J. George*,c
a. Laboratory of Macromolecular and Organic Chemistry and Institute for Complex Molecular Systems (ICMS),
Eindhoven University of Technology, PO Box 513, 5600 MB, Eindhoven, The Netherlands
b. Chemistry and Physics of Materials Unit, Jawaharlal Nehru Center for Advanced Scientific Research (JNCASR),
Jakkur, Bangaluru-560064, India
c. Supramolecular Chemistry Laboratory, New Chemistry Unit, JNCASR, Jakkur, Bangaluru-560064, India
ABSTRACT: Control over the helical organization of synthetic supramolecular systems is intensively pursued to manifest
chirality in a wide range of applications ranging from electron spin filters to artificial enzymes. Typically, switching the
helicity of supramolecular assemblies involves external stimuli or kinetic traps. However, efforts to achieve helix reversal
under thermodynamic control and understanding the phenomena at a molecular level are scarce. Here we present a
unique example of helix reversal (stereomutation) under thermodynamic control in the self-assembly of coronene bisi-
mide (CBI-35CH) which has a 3,5-dialkoxy substitution on imide phenyl groups leading to “molecular pockets” in the as-
sembly. The stereomutation was observed only if the CBI monomer possesses molecular pockets. Detailed chiroptical
studies performed in alkane solvents with different molecular structure reveal that solvent molecules intercalate or form
clathrates within the molecular pockets of CBI-35CH at low temperature (263 K), thereby triggering the stereomutation.
The interplay between helical assembly, molecular pockets and solvent molecules is further unraveled by explicit solvent
molecular dynamics simulations. Our results demonstrate how the molecular design of self-assembly building blocks can
orchestrate the organization of surrounding solvent molecules, which in turn dictates the helical organization of the re-
sulting supramolecular assembly.
Introduction:
chains and low helix reversal barrier exhibit switchable
helical behaviour. Supramolecular polymers are inherent-
ly more dynamic than covalent counterparts due to the
weak non-covalent interaction between the monomeric
units27 and are thus more suited for harnessing the dy-
namic helicity. Stereomutation has been observed in a
variety of supramolecular systems and it can be broadly
divided into two categories; i) due to stimuli such as pH,28
light,15 guests,29-31 solvents,32,33 and coassembly34 and ii)
due to kinetic traps or pathway complexity. The investiga-
tion into the latter category of systems has steeply in-
creased in the last few years. The process of self-assembly
of a monomer into more than one kind of aggregates with
at least one of them being a kinetic state has been termed
as “pathway complexity”35 and it has been observed in
Helical assemblies are ubiquitously found in nature and
have been a source of inspiration for chemists to emulate
elegant optically active architectures.1-3 The molecular
recognition and catalytic activity of bio-macromolecules
rely heavily on their three-dimensional helical structure.4,5
Synthetic helical structures can act as mimics to biologi-
cal counterpart aiding to elucidate the role of chiral or-
ganization in biological functions. In addition, the chirali-
ty of a system is pivotal in realizing new applications such
as molecular motors6 and spin-filters7,8. Thus control over
the helicity of macromolecules has been a topic of intense
study. Synthetic helical structures are typically obtained
through three approaches; i) conformationally restricted
macromolecules,9-11 ii) self-assembly of chiral mono-
mers/polymers12 and iii) induction of chirality to assem-
bled structure through chiral solvents,13,14 circularly polar-
ized light,15 and chiral auxillary16.
self-assembled
systems
such
as
oligo(p-
phenylenevinylene),36 merocyanines,37 bipyridine substi-
tuted benzene-1,3,5-tricarboxamides (BTA),38 perylene
bisimides,39 triphenylamines,40 porphyrins,41 oligo(p-
phenylene)42 and N-heterotriangulenes43 among others.
Kinetic control by mastering pathway complexity can lead
to living-supramolecular polymerization as demonstrated
by Takeuchi, Sugiyasu et al.44,45 Recently, transient helici-
Stereomutation or dynamic switching of helicity is an
important tool to control the helicity of an assembly. Co-
valent polymers such as regioregular poly(thiophene)s,17
poly(β-phenylpropyl L-aspartate),18 poly(silane)s19-22 and
poly(quinoxaline-2,3-diyl)s23-26 with pendant chiral side
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ty or fuel-driven stereomutation has also been observed
for out-of-equilibrium self-assembly.46
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The thermodynamic and/or kinetic stability of a system
depends on experimental conditions of self-assembly such
as (co)-solvent and temperature. Solvent molecules have
been shown to play a major role in the assembly
process.47-49 In addition, the observation of chiral solvents
inducing helicity into achiral assemblies14,50,51 further con-
firms the active role of solvents in the self-assembly pro-
cess. Moreover, there have been studies in which opposite
helical bias is observed under thermodynamic control by
the participation of apolar solvents (linear vs
branched)33,52 or mixture of two polar solvents32,53,54. How-
ever, systems where stereomutation under thermodynam-
ic control is directed by the molecular design of the build-
ing blocks that governs the organization of solvent mole-
cules have not been reported.
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Figure 1: a) Molecular structure of the coronene bisimides
(CBIs) involved in this study. b) Schematic representation of
the self-assembly of CBI-35CH. The phenoxy group on one of
the imides is colored magenta, highlighting the molecular
pocket that is formed in the periphery of the assembly. Only
one possible helicity is shown.
Here we present an example of a synthetic helical as-
sembly in which solvent molecule incorporation into a
molecular pocket leads to dynamic stereomutation at low
temperature, analogous to binding of guest molecules to
enzymes leading to significant conformational change,
thus modulating their activity. During the course of our
investigation on the self-assembly of coronene bisimides
(CBIs),55 we serendipitously observed the helix inversion
for CBI derivative (CBI-35CH) possessing a bis((S)-3,7-
dimethyloctyloxy)phenyl substituent on the imide posi-
tion. Due to the 3,5-position of the alkoxy chains on the
phenyl, the molecule possesses a cavity or pocket accessi-
ble to solvents. We have investigated this dynamic stere-
omutation process in detail by electronic circular dichro-
ism studies by varying the molecular structure of mono-
mer and solvent used for self-assembly to understand the
origin of helix inversion. Remarkably, the stereomutation
is completely under thermodynamic control and reversi-
ble. Based on explicit solvent molecular dynamics (MD)
simulations and experimental studies, we show that the
solvent-accessible pocket in CBI-35CH assembly is re-
sponsible for the helix inversion. Thus the present work
exemplifies the role of monomer structure and solvents in
dictating the handedness of a supramolecular assembly.
perimental section for details). The synthesis and charac-
terization of CBI-GCH and CBI-GACH has been reported
before.55
Self-assembly of CBI-35CH
The self-assembly of all the coronene bisimides has
been studied mainly through UV/vis absorption and elec-
tronic circular dichroism (CD) spectroscopy in apolar
solvents. Both CBI-35CH and CBI-35ACH are weakly-
fluorescent even in the molecularly dissolved state due to
electron transfer from the phenoxy wedge to the CBI core,
as observed in the case of CBI-GCH and CBI-GACH.55
UV/vis absorption spectrum of CBI-35CH in MCH (c =
5×10-5 M) at 288 K shows a maximum at 325 nm with
broad band between 450 to 550 nm. At higher tempera-
ture, the absorption maximum red-shifts to 332 nm with
the appearance of a shoulder and the bands at 450, 477,
and 488 nm become sharp (Figure 2a). The hypsochromic
shift in absorption maximum at low temperatures sug-
gests the H-type aggregation of CBI-35CH in MCH. The
corresponding CD spectra at 288 K shows a bisignated
Cotton effect with almost equal magnitude of the molar
circular dichroism (with ∆ε of –14.9 and +13.36 L mol–1 cm–
Results:
The molecules under study consist of a coronene bisi-
mide core with phenoxy substituents on imide positions
(Figure 1a). The phenoxy moiety with 3,5-dialkoxy substi-
tution (both chiral (CBI-35CH) and achiral (CBI-35ACH))
and 3,4,5-trialkoxy substitution (gallic moiety, both chiral
(CBI-GCH) and achiral (CBI-GACH)) have been investi-
gated. The 3,5-disubstitution creates a molecular pocket
in the resulting assemblies for the incorporation of guest
or solvent molecules (Figure 1b). CBI-35CH and CBI-
35ACH were synthesized by the imidation of coronene
dianhydride56 with the corresponding phenyl amine in
freshly distilled quinoline and both the molecules were
1
at 320 and 361 nm, respectively, Figure 2b), indicating
that the chirality of the side chains has been transferred
to the supramolecular level. The zero crossing points in
the CD spectrum (at λ = 476, 463 and 328 nm) coincide
with the maxima in the UV/vis absorption spectrum (at λ
= 478, 468 and 328 nm), indicating that the CD spectrum
originates from exciton coupling between the neighboring
CBI molecules. Since the Cotton effect has a positive cou-
plet at the longer wavelength (around 500 nm), the as-
semblies have been ascribed to (P)-type helicity. At higher
temperatures (368 K) the Cotton effect vanishes, due to
the lack of interaction between monomers leading to a
molecular dissolved state (Figure 2b). Thus, the self-
assembly of
1
thoroughly characterized using H- and 13C-NMR spec-
troscopy and MALDI-TOF mass spectrometry (see SI ex
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Figure 2: Self-assembly of CBI-35CH. a) and b) temperature-dependent UV/vis and CD spectra, respectively, of CBI-35CH
in MCH (c = 5×10–5 M). Arrows indicate spectral changes with decrease in temperature. c) Tapping mode atomic force mi-
croscopy (AFM) image of a film of CBI-35CH obtained by drop-casting a solution in MCH (c = 1×10–4 M) on a clean glass
substrate. d) Height profile analysis along the lines marked in c).
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CBI-35CH is primarily driven by the π-π stacking of the
coronene bisimides and the van der Waals interactions of
the peripheral phenoxy wedges.
parameters governing the self-assembly have been ob-
tained from non-linear regression analysis of cooling
curves and Van’t Hoff plots at various concentrations
(Figure S2) and are detailed in Supporting Information
Table S1. The melting temperature (Tm) of the assembly
changes by 10 K over an order of magnitude change in
concentration.
The CBI-35CH assemblies were visualized using tap-
ping mode atomic force microscopy (AFM) on a thin film
(obtained by drop-casting a 1×10–4 M solution in MCH) on
a freshly cleaned glass substrate. The microscopy images
display a network of fibrillar structures on a micrometer
length scale (Figure 2c). This suggests the 1-D self-
assembly of CBI-35CH. The height profile showed dimen-
sions in the range of 0-30 nm for various fibers (Figure
2d). The individual molecular dimensions are much
smaller (~0.6 nm) than those obtained upon height analy-
sis, suggesting that the fibers observed in AFM are rather
bundles of multiple individual fibers. Also, the macromo-
lecular helicity of the bundles was not discernible through
AFM studies.
After visualizing the 1-D assembly of CBI-35CH, we in-
vestigated the mechanism of supramolecular polymeriza-
tion using temperature-dependent CD studies at various
concentrations. Cooling curves obtained by monitoring
the Cotton effect at 320 nm at different cooling rates (0.5,
1 and 2 K min–1) were identical (Figure S1), indicating that
the supramolecular polymerization occurs under thermo-
dynamic control. The cooling curves showed a gradual
transition from monomers at high temperature to self-
assembled state at 283 K. The normalized cooling curves
could be well described by the isodesmic model57 of self-
assembly (Figure 3). Further, the various thermodynamic
Figure 3: Mechanism of self-assembly of CBI-35CH in MCH.
The normalized fraction of aggregates (α) as a function of
temperature, was obtained from temperature-dependent CD
cooling studies (cooling rate 2 K min–1).
Dynamic reversal of supramolecular chirality in
MCH
When the solution of CBI-35CH in MCH was cooled
below 283 K, we observed that the sign of the Cotton ef-
fect reversed (Figure 4a). Intrigued by this reversal of the
sign, the CD cooling curves were recorded till 263 K at
various concentrations. The reversal of supramolecular
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Figure 4: Stereomutation of CBI-35CH assemblies in MCH at lower temperatures. a) Cooling curves at different concentra-
tions obtained from CD studies (cooling rate = 2 K min–1). b) and c) Variable-temperature CD and UV/vis spectra respective-
ly (c = 5×10–5 M) from 283 K to 263 K (spectra are shown every 2 K). Arrow indicates spectral changes with decrease in tem-
perature. d) Time-dependent CD spectra (c=5×10–5 M) at 273 K and 268 K immediately after solution preparation and after 5
days, indicating that both the states are under thermodynamic control. All studies were performed in a 10 mm path length
cuvette.
helicity (or sign of Cotton effect) was observed at all con-
centrations (Figure 4a and Figure S3), albeit that the tem-
perature at which the CD signal crosses zero (termed as
transition temperature, T0) increased with increase in
concentration (Figure S4). A temperature versus concen-
tration pseudo-phase diagram was constructed to exam-
ine the concentration dependence of both self-assembly
and stereomutation process, as has been previously re-
ported for (D)-BTA.33 The T0-line shows a much weaker
dependence on concentration compared to the Tm-line
(Figure S5). The weak but finite concentration-
dependence of the stereomutation process suggests that
the degree of polymerization or stack length affects the
stereomutation process.
tween 283 and 263 K (Figure 4c). This clearly indicates
that inversion in supramolecular helicity is not due to
further self-assembly of CBI-35CH.58 Often, such reversal
of helicity in supramolecular systems have been attribut-
ed to kinetic processes.36 To examine that, we have rec-
orded full cooling and heating curves at three different
rates (i.e. 0.5, 1 and 2 K min-1). All the cooling and heating
curves coincide over the entire spectral range (Figure S7).
CD spectra in MCH (c = 5×10–5 M) corresponding to the
(P)-(at 273 K) and (M)-helicity (at 268 K) were identical
even after keeping solution at room temperature for 5
days (Figure 4d). This suggests that the (M)-helicity ob-
served at low temperature does not depend on the path
taken to reach it, but corresponds to another thermody-
namic state determined solely by temperature.
CD and UV/vis spectra were recorded every 2 K to ob-
serve the spectral changes as a function of temperature.
The stereomutation process is evident from the CD spec-
tra which show isodichroic points at λ = 469, 432, 329,
and 309 nm (Figure 4b). The CD spectra at 283 K and 263
K are not exact mirror images of each other, indicating
that the (M)-supramolecular helicity at 263 K is diastere-
omerically related to the (P)-helicity observed at higher
temperatures. On further decreasing the temperature to
218 K, the sign of the Cotton effect was retained and only
the magnitude increased (Figure S6). Remarkably, the
UV/vis absorption spectra do not show any change be-
Table 1: Thermodynamic parameters for the self-
assembly of CBI-35CH in MCH.
Enthalpy,
∆H
(kJ mol–1)
Entropy,
∆S
(kJ mol–1K–1)
Free energy,
∆G
(kJ mol–1)[b]
–67.77[a]
–0.146[a]
–26.45
[a] These are average values taken from Table S1 and [b] Cal-
culated at 283 K.
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Figure 5: CD studies on the stereomutation of CBI-35CH assemblies in cyclic and linear solvents. a) Cooling curves obtained
from CD studies of CBI-35CH in various cyclic solvents (c = 5×10–5 M, 2 K min–1). b) Plot of transition temperature (the tem-
perature at which the CD effect is zero while cooling from high to low temperature, obtained from Figure 5a) versus the
crystallization temperature of respective solvent (melting point). c) CD spectra of CBI-35CH in n-heptane (c = 6.5×10–5 M) at
low-temperatures. d) A schematic representation of the solvent intercalation into the molecular pocket at low temperature
leading to helicity reversal. MCH, being a cyclic solvent, fits into the pocket better compared to n-heptane for which a small
cluster of molecules is needed to completely occupy the molecular pocket.
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Solvent effect in reversal of helicity
magnitude. Further decrease in temperature resulted in
the complete inversion of supramolecular helicity with
several isodichroic points (Figure 5c), indicating the exist-
ence of only two kinds of chiral assemblies. Again mini-
mal changes were observed in the UV/vis absorption
spectra at low temperatures (Figure S13). We envisage
that, due to the linear structure of n-heptane, a finite
number of solvent molecules or a small molecular cluster
of n-heptane would be required to completely satisfy the
molecular pocket of CBI-35CH through intercalation
(Figure 5d). The process of forming a cluster of n-heptane
within the pocket of CBI-35CH requires lower tempera-
ture, also resulting in a significantly lower transition tem-
perature (~253 K) with n-heptane as the solvent.60
After confirming that the inversion in helicity does not
correspond to kinetically trapped or metastable states, we
have further studied the role of solvent to get better in-
sight into the helix inversion. CD cooling curves were
recorded in a range of cyclic solvents such as cyclohexane
(Figure S8), cis- and cis/trans-1,2-dimethylcyclohexane
mixture (Figure S9 & 10) and cis/trans-decalin mixture
(Figure S11). The inversion in helicity was observed in all
the solvents but the transition temperature is different for
each of the solvents. Surprisingly, a plot of transition
temperature versus the crystallization temperature of the
cyclic solvents59 shows a linear trend (Figure 5b, R2
=
0.96). One plausible explanation of the linear trend would
be the following; intercalation of solvent molecules into
the molecular pockets available in the phenoxy part of
CBI-35CH assembly, leading to its rigidification at low
temperatures, is a process analogous to crystallization.
The inversion of chirality was also observed in branched
solvents such as iso-octane (Figure S12). In all the cases,
no change in UV/vis absorption spectra was observed
going from (P)- to (M)-helicity.
Role of molecular structure
The conjecture that the molecular pockets in CBI-35CH
self-assembly play a dominant role in controlling the helix
reversal was examined by CD studies of similar CBI deriv-
atives with structural mutations in the gallic moiety. First
the 3,4,5-tris((S)-3,7-dimethyloctyoxy)phenyl substituted
CBI (CBI-GCH) which does not possess a molecular
pocket was studied by CD spectroscopy at low tempera-
tures. CBI-GCH was earlier observed to form (P)-type
helix in MCH in the assembled state,55 analogues to the
chiroptical behavior of CBI-35CH assembly.
In addition to cyclic and branched solvents, self-
assembly of CBI-35CH was also studied in a linear chain
alkane such as n-heptane. Unlike the cyclic solvents, no
inversion in handedness was observed for CBI-35CH in n-
heptane (c = 6.5×10–5 M) until 263 K. On decreasing the
temperature to 253 K, the Cotton effect decreased in
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Figure 7: Assembly of achiral CBI derivatives with chiral
solvent. CD spectra of CBI-35ACH and CBI-GACH in (S)-
limonene at 263 K (c = 5×10-5 M). The molecular structure of
the substitution pattern on gallic moiety are shown in the
inset of b).
till 293 K although aggregation sets in earlier (Figure S15).
On further cooling from 293 K to 263 K the induced Cot-
ton effect is observed without significant changes in the
absorption spectra (Figure S16). This clearly suggests that
once the CBI-35ACH reaches a certain extent of aggrega-
tion then the chiral solvent molecules intercalates into
the pocket of the assembly leading to induced bisignate
Cotton effect (Figure 7). Induced CD spectrum for CBI-
35ACH observed in (R)-limonene was exactly the mirror
image of that recorded in (S)-limonene (Figure S17), thus
reaffirming that the CD spectra are due to the chirality
transfer from solvent to the chromophore (CBI). On the
other hand, similar studies on CBI-GACH (with 3,4,5-
trialkoxy phenyl) showed only a very weak induced Cot-
ton effect between 305-350 nm (Figure 7). The molar el-
lipticity (∆ε) at 322 nm for CBI-35ACH and CBI-GACH in
(S)-limonene are –11.68 and –1.6 L mol–1 cm–1, respectively
(Figure 7). The difference in the extent of chiral induction
(∆ε) between the CBI-35ACH and CBI-GACH clearly in-
dicates the increased proximity of solvents with the CBI
core through the molecular pocket for the former. Thus,
the influence of molecular pocket is also reflected in the
extent of chiral induction by (S)-limonene.
Figure 6: Helical assembly of CBI derivative with no molecu-
lar pocket. Variable-temperature CD spectra of CBI-GCH in
MCH (a) and n-heptane (b) do not show stereomutation at
low temperatures (c = 5×10–5 M). Inset of a) shows the struc-
ture of gallic substitution pattern.
CD spectra of CBI-GCH in both cyclic (MCH) and linear
(n-heptane) solvents retained the (P)-helicity until 235 K
(Figure 6a and b), in contrast to the reversal observed for
CBI-35CH at such low temperatures. We envisage that,
due to the closely substituted alkyl chains in the gallic
wedge, CBI-GCH lacks a molecular pocket and thus the
approach of solvent molecules into CBI-GCH assembly
will be hindered. This further shows the important role of
the molecular pocket in dictating the reversal.
Furthermore, the role of molecular pocket was investigat-
ed by CD studies of achiral CBIs with both 3,5- and 3,4,5-
alkoxyphenyl substituents on the imide region in chiral
solvents to investigate the efficiency of chiral induction
based on molecular structures. Previously, it has been
shown that preferential solvation of a supramolecular
assembly by chiral solvents leads to chiral induction,14,50,51
thus showing that proximity of chiral solvent is important
to achieve induction of chirality. CBI-35ACH forms H-
type aggregates in MCH, similar to that observed for the
CBI-35CH (Figure S14). On cooling a solution of CBI-
35ACH in (S)-limonene from molecularly dissolved state
(~368 K) to 293 K, the UV/vis spectra show characteristics
of self-assembly. The normalized fraction of aggregates
(α) at 293 K obtained from CD and UV/vis cooling curve
are 0.04 and 0.78, respectively (Figure S15b). This indi-
cates that chiral induction does not take place
Molecular dynamics (MD) simulations
In order to gain a molecular level understanding of the
interplay between CBI assemblies and solvent molecules,
molecular dynamics simulations were carried out. Pre-
formed (M)- and (P)-stacks of size 15 were soaked in well-
equilibrated cyclohexane solvent for 5 ns. Given the small
system size and high concentration, it is difficult to ob-
serve the reversal of handedness in the MD simulation at
temperatures used in the experiments. Thus, two extreme
temperatures (250 K and 350 K) have been chosen to un-
derstand the stereomutation process. Simulations were
performed in isothermal-isobaric ensemble (NPT) for 20
ns and the last 12 ns were used for all the analysis. Addi-
tional simulation details are given in Supporting Infor-
mation.
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Figure 8: Molecular dynamics (MD) simulations on intercalation of MCH solvent molecules within molecular pocket of
CBI-35CH assemblies: a) Pictorial representation of the distance between the center of mass of chiral carbon atom on the
phenoxy wedge to the center of mass of the solvent molecule (MCH). b) The distance defined in a) was used to obtain the
pair correlation (g(r)) plotted at different temperatures. See supporting information Figure S18 for the full g(r) graph. c)
Probability distribution of CBI-35CH as a function of dihedral angle. The Scanned dihedral angle is shown in the inset. d) A
pictorial representation of the stereomutation process. At 283 K, the solvent molecules form a sheet around an assembly,
whereas at 263 K the solvents intercalate or form clathrates with assembly leading to inversion of helicity.
To quantify the occupation of solvent molecules in the
pocket of CBI-35CH, the pair correlation function (g(r))
between the center of mass of solvent molecules and the
center of mass of stereocenters on one of the arms of CBI-
35CH molecules (Figure 8a) at 250 K was compared to 350
K. At 250 K, solvent molecules can intrude deeper into the
pocket of a (M)-stack (2.85 Å) than a (P)-stack (3.3 Å),
favoring (M)-type helicity (Figure 8b and Figure S18).
However, at 350 K, the g(r) peaks at exactly the same dis-
tance for both (P)- and (M)- stacks (Figure 8b). As a re-
sult, at elevated temperatures the solvent interaction with
CBI-35CH molecules is similar for (M)- and (P)-stacks,
and the chirality present in the side chains determines the
handedness of the oligomer, favoring (P)-type helicity.
crease with decreasing temperature (Figure 8c), thus wid-
ening the pocket for approach of solvent molecules. This
again points to the increased probability of accommodat-
ing the solvent molecules at low temperature. Further,
semi-empirical (ZINDO) based computation on (P)- and
(M)-dimer obtained from MD-simulation exhibit opposite
helicity (Figure S20), which is in accordance with reversal
of supramolecular chirality observed for CBI-35CH (Fig-
ure 4b).
To corroborate the effect of solvent intercalation on the
helicity at low temperature, simulations were performed
for CBI-GCH, which lacks a molecular pocket. Pair corre-
lation function (g(r)) between the center of mass of sol-
vent molecules and center of mass of stereocenters on
one of its arm show negligible difference at two tempera-
tures (see Figure S21). This clearly indicates that even at
low temperatures the solvent molecules do not intercalate
into the assembly of CBI-GCH. The g(r) peaks at ~3 Å and
9 Å for CBI-35CH and CBI-GCH, respectively, further
reaffirming the proximal distance of solvents molecules to
assembly of CBI-35CH.
Distance distributions between the chiral centers of ad-
jacent molecules within the same helix were determined
(Figure S19). At lower temperatures, these distributions
are narrow and short, indicative of chiral centers that
strongly interact while at the same time leaving the mo-
lecular pocket wider. At high temperatures, interaction
between the chiral centers is weak and thus, the tails are
disordered resulting in decreased pocket accessibility.
Furthermore, using the dihedral angle as depicted in inset
of Figure 8c, we have quantified the dihedral angles of
four arms for (M)-stack at 250 K and (P)-stack at 350 K.
Trans-conformation of the dihedral angle (around ±180°)
refers to a wider pocket while gauche-conformation
(around ±80°) hints towards a decreased accessibility of
the pocket. It is evident that the trans-conformations in-
Discussion:
The stereomutation observed for CBI-35CH assembly at
low temperature can be attributed to the molecular pock-
et of CBI-35CH due to the following reasons; i) The stere-
omutation is observed in various cyclic alkane solvents
and the transition temperature (T0) correlates directly to
the crystallization temperature of the solvents, indicating
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Author Contributions
that a process similar to crystallization of solvents is oc-
curring. ii) CBI-GCH, which lacks a molecular pocket,
does not show stereomutation until 235 K in both linear
and cyclic alkane solvents. iii) The induction of chirality
to an assembly of achiral CBI-35ACH from solvents such
as (S)-limonene occurs only at low-temperature (<293 K).
This suggests that – similar to cyclic alkanes, (S)-
limonene molecules enter the molecular pocket at lower
temperatures, and induce chirality to the system. This is
further strengthened by the fact that for achiral CBI-
GACH, which lacks a molecular pocket, the extent of chi-
ral induction is 10 times lower compared to CBI-35ACH.
iv) Finally, explicit solvent MD simulations show that for
CBI-35CH the solvent molecules approach the pocket
much closer at low temperature. For CBI-GCH however,
MD simulations show a solvent approach as well as hand-
edness of the assembly that is invariant of the tempera-
ture. Thus, based on these results we envisage that CBI-
35CH assemblies and solvent molecules form clathrates or
inclusion complexes at low-temperature (<283 K) leading
to inversion in handedness of the assembly (Figure 8d).
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All authors have given approval to the final version of the
manuscript.
Funding Sources
The authors thank JNCASR and DST, India and the Dutch
ministry of education, culture and science (FMS Gravitation
program 024.001.035) for financial support. C. Kulkarni
thanks Marie Skłodowska-Curie (704830) post-doctoral fel-
lowship for financial support.
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ACKNOWLEDGMENT
C. Kulkarni, K. K. Bejagam and S. J. George thank Prof. S.
Balasubramanian of JNCASR for access to computational
facility and for fruitful discussions. C. Kulkarni thanks Krish-
nendu Jalani for providing coronene dianhydride starting
material and Dr. Umesh Mogera for AFM measurements.
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ASSOCIATED CONTENT
Supporting Information. Synthesis and characterization
details of CBI-35CH and CBI-35ACH, supporting figures and
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AUTHOR INFORMATION
Corresponding Author
*subi@jncasr.ac.in and e.w.meijer@tue.nl
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(58) It has been previously shown that kinetic studies are
needed to unambigiously assign inter vs intra-assembly
processess.38 However, due to the very low operating
temperature, such studies were not successful. Based on
negligible change in UV-vis spectra, we attribute the helical
transition to intra-assembly process.
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