Solvent-induced helical assembly and reversible chiroptical switching of chiral cyclic-dipeptide-functionalized naphthalenediimides

Article abstract of DOI:10.1002/chem.201303123

Understanding the roles of various parameters in orchestrating the preferential chiral molecular organization in supramolecular self-assembly processes is of great significance in designing novel molecular functional systems. Cyclic dipeptide (CDP) chiral auxiliary-functionalized naphthalenediimides (NCDPs 1-6) have been prepared and their chiral self-assembly properties have been investigated. Detailed photophysical and circular dichroism (CD) studies have unveiled the crucial role of the solvent in the chiral aggregation of these NCDPs. NCDPs 1-3 form supramolecular helical assemblies and exhibit remarkable chiroptical switching behaviour (M- to P-type) depending on the solvent composition of HFIP and DMSO. The strong influence of solvent composition on the supramolecular chirality of NCDPs has been further corroborated by concentration and solid-state thin-film CD studies. The chiroptical switching between supramolecular aggregates of opposite helicity (M and P) has been found to be reversible, and can be achieved through cycles of solvent removal and redissolution in solvent mixtures of specific composition. The control molecular systems (NCDPs 4-6), with an achiral or D-isomer second amino acid in the CDP auxiliary, did not show chiral aggregation properties. The substantial roles of hydrogen bonding and π-π interactions in the assembly of the NCDPs have been validated through nuclear magnetic resonance (NMR), photophysical, and computational studies. Quantum chemical calculations at the ab initio, semiempirical, and density functional theory levels have been performed on model systems to understand the stabilities of the right (P-) and left (M-) handed helical supramolecular assemblies and the nature of the intermolecular interactions. This study emphasizes the role of CDP chiral auxiliaries on the solvent-induced helical assembly and reversible chiroptical switching of naphthalenediimides.

Full text of DOI:10.1002/chem.201303123

FULL PAPER
DOI: 10.1002/chem.201303123
Solvent-Induced Helical Assembly and Reversible Chiroptical Switching of
Chiral Cyclic-Dipeptide-Functionalized Naphthalenediimides
Shivaprasad Manchineella,[a] V. Prathyusha,[b] U. Deva Priyakumar,*[b] and
T. Govindaraju*[a]
Abstract: Understanding the roles of
various parameters in orchestrating the
preferential chiral molecular organiza-
tion in supramolecular self-assembly
processes is of great significance in de-
signing novel molecular functional sys-
tems. Cyclic dipeptide (CDP) chiral
auxiliary-functionalized naphthalene-
diimides (NCDPs 1–6) have been pre-
pared and their chiral self-assembly
properties have been investigated. De-
tailed photophysical and circular di-
chroism (CD) studies have unveiled
the crucial role of the solvent in the
chiral aggregation of these NCDPs.
NCDPs 1–3 form supramolecular heli-
cal assemblies and exhibit remarkable
chiroptical switching behaviour (M- to
P-type) depending on the solvent com-
position of HFIP and DMSO. The
strong influence of solvent composition
on the supramolecular chirality of
NCDPs has been further corroborated
by concentration and solid-state thin-
film CD studies. The chiroptical switch-
ing between supramolecular aggregates
of opposite helicity (M and P) has
been found to be reversible, and can be
achieved through cycles of solvent re-
moval and redissolution in solvent mix-
tures of specific composition. The con-
trol molecular systems (NCDPs 4–6),
with an achiral or d-isomer second
amino acid in the CDP auxiliary, did
not show chiral aggregation properties.
The substantial roles of hydrogen
bonding and p–p interactions in the as-
sembly of the NCDPs have been vali-
dated through nuclear magnetic reso-
nance (NMR), photophysical, and com-
putational studies. Quantum chemical
calculations at the ab initio, semiempir-
ical, and density functional theory
levels have been performed on model
systems to understand the stabilities of
the right (P-) and left (M-) handed
heliACTHNUTRGENUGcN al supramolecular assemblies and
the nature of the intermolecular inter-
actions. This study emphasizes the role
of CDP chiral auxiliaries on the sol-
vent-induced helical assembly and re-
versible chiroptical switching of naph-
thalenediimides.
Keywords: chiroptical switching
circular dichroism · cyclic dipep-
tides · naphthalenediimides · self-
assembly · supramolecular chirality
·
AHCTUNGTRENNUNG
Introduction
nature of such materials and the ease with which their struc-
tural and functional properties may be tuned compared to
covalent polymers.[3] The characteristic feature of such
supramolecular polymers is the assembly of p-conjugated
and aromatic monomer units with stabilization through hy-
drogen bonding and p-stacking interactions. Induction of
helical chirality in supramolecular polymers through struc-
tural variations at the molecular self-assembly level is chal-
lenging due to the interplay of multiple noncovalent interac-
tions. In general, the noncovalent synthesis of supramolec-
ular polymers can be modulated through external stimuli ca-
pable of influencing the mode of molecular self-assembly. In
this context, previous literature reports suggest that helical
handedness in a self-assembly system can be achieved by
employing similar external stimuli and chiral auxiliaries.[4]
External stimuli such as temperature, light, solvent, and ad-
ditives have been successfully used to control the chiral
handedness of synthetic oligomers and polymers.[5–8] Some
of the successful reports on chiral modulation in noncova-
lent systems have dealt with solvent-modulated supramolec-
ular chirality of merocyanines, squarine dyes, and benzene-
tricarboxylic acid derivatives.[9–11]
Helical chirality is ubiquitous in biological systems, as seen
in DNA and proteins.[1] The helical conformations adopted
by synthetic oligomers and polymers are pertinent to various
applications, such as chiral recognition, asymmetric catalysis,
chiral separation, and chiroptical switching.[2] In recent
times, helical chirality in supramolecular polymers has at-
tracted considerable interest due to the intrinsic dynamic
[a] S. Manchineella, Dr. T. Govindaraju
Bioorganic Chemistry Laboratory, New Chemistry Unit
Jawaharlal Nehru Centre for Advanced Scientific Research
Jakkur, Bangalore 560064 (India)
Fax : (+91)80-2208-2627
E-mail: tgraju@jncasr.ac.in
[b] V. Prathyusha, Dr. U. D. Priyakumar
Centre for Computational Natural Sciences and Bioinformatics
International Institute of Information Technology
Hyderabad 500032 (India)
E-mail: deva@iiit.ac.in
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201303123: Synthetic procedures
and characterization of NCDP 1–6, experimental details, UV/Vis ab-
sorption, emission, and CD data, theoretical calculations, and models
of NCDPs.
Naphthalenediimide (NDI), the bis-imide derivative of
1,4,5,8-naphthalenetetracarboxylic dianhydride (NDA), is an
Chem. Eur. J. 2013, 19, 16615 – 16624
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
16615

extremely useful molecular platform with applications rang-
ing from organic electronics to biomedicine.[12] The possibili-
ty of selective imide functionalization, high p-acidity, planar-
ity conducive to strong p–p interactions, and ease of pro-
Results and Discussion
We synthesized CDPs [cyclo(l-Lys-l-Tyr), cyclo(l-Lys-l-
Phe), cyclo(l-Lys-l-Leu), cyclo(l-Lys-Gly), cyclo(l-Lys-d-
Tyr), and cyclo(l-Lys-d-Phe)] from the corresponding linear
dipeptides, retaining l-lysine as one of the amino acids and
varying the second amino acid to obtain a-substituents with
the required stereochemistry (Figure 1).[24a] These CDP aux-
iliaries were condensed with NDA through the e-amine
group of lysine to obtain NCDPs 1–6, respectively, in good
to excellent yields (Schemes S1–S6 in the Supporting Infor-
mation). All of the NCDPs were characterized by NMR
spectroscopy, elemental analysis, and mass spectrometry. Ini-
ACHTUNGTRENNUNGcessability of these systems in solution has led to increased
demand for the design of novel NDI-based supramolecular
systems. Imide substituents studied have included alkyl
chains, aromatic rings, amino acids, dipeptides, and a combi-
nation of alkyl chains and amino acids.[13–21] Our recent work
demonstrated the potential of a biomimetic strategy based
on amino acid- and peptide-functionalized NDIs for design-
ing 0D, 1D, and 2D molecular materials with interesting
structural and functional properties.[12e,20,21] The functional
relevance of these biomimetic molecular materials varied
from attolitre containers for miniaturized biological assays
to organic electronics to self-cleaning functional molecular
materials.[12e,20] Furthermore, the amino acid- and dipeptide-
functionalized NDIs emphasized the significance of the
chiral centre of the amino acid directly attached to the
imide nitrogen in controlling the supramolecular helical
chirality of the derived self-assembled structures.[21] Subse-
quently, the chiroptical properties of these systems revealed
significant chiral transcription, amplification, and retentive
helical memory with probable implications for the origin of
homochirality in Nature.[1c]
Cyclic dipeptides (CDPs) are the smallest possible cyclic
forms of peptides and are known for their unique structural
properties and diverse biological functions.[22] By virtue of
their structural rigidity, propensity for strong intermolecular
hydrogen bonding, molecular recognition, and resistance to-
wards proteolytic enzymes, CDPs constitute good supra-
molecular synthons for the preparation of soft organogels,
hydrogels, and well-defined nanoarchitectures for various
applications.[23–25] We envisaged an inclusive molecular
design based on NDI with CDP chiral auxiliaries as mono-
mers for the noncovalent synthesis of helical supramolecular
polymers. The NDI-CDP (NCDP) conjugates serve as
model systems to evaluate the role of chiral centres on the
imide substituents located several atoms away from the
imide nitrogen in inducing specific helical assemblies of
NDI. This study complements our earlier work, in which the
chiral centre of the first amino acid directly attached as the
imide substituent through the a-amino group was found to
determine the outcome of the helical assembly of NDIs.[20,21]
The NCDP molecular platform has also assisted our under-
standing of the influence of a-substituents and the corre-
sponding chiral centres in CDP auxiliaries. Herein, we
report novel symmetrical NCDPs (1–6) as new molecular
platforms to engineer NDI chiral assembly through aromatic
(NDI) and hydrogen-bonding (CDP) interactions. Further-
more, this study emphasizes the significance of chiral auxil-
iaries and the decisive role played by solvent composition in
modulating the helical supramolecular self-assembly of such
systems.
Figure 1. Top: Molecular structures of naphthalenediimides with different
CDP auxiliaries (NCDPs 1–6). Bottom: Model of monomer NCDP 1 and
its M-helical and P-helical organization in HFIP and DMSO/HFIP, re-
spectively.
16616
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 16615 – 16624

Chiroptical Switching in Naphthalenediimide-Based Biomimetics
FULL PAPER
tially, we chose NCDP 1 with l-tyrosine as the second
amino acid of the CDP auxiliary for our detailed study
owing to the characteristic self-assembling properties of l-
tyrosine when present in polymer chains and the strong in-
termolecular interactions among cyclo(l-Tyr-l-Lys) deriva-
tives.[25] The molecular interactions and chiral aggregation
properties of NCDP 1 were studied by UV/Vis absorption
and CD spectroscopic measurements in 1,1,1,3,3,3-hexafluo-
increasing the concentration of the solution to 100 mm, indi-
cating M-helical (left-handed) assembly of NCDP 1 (Fig-
ure 2b). Negative Cotton signals were consistently observed
for all concentrations of the solution (100–500 mm), indicat-
ing no interference with the chiral aggregation due to con-
centration effects. Furthermore, it should be noted that the
CD spectra on the molar ellipticity scale (data not shown)
showed similar CD signal intensity, which clearly demon-
strated that the chiroptical switching was independent of
concentration. The observed M-helical bias of NCDP 1 may
be ascribed to the aggregation of molecules (ꢀ100 mm) and
preferential stabilization of one of the helical forms (M-
type) by HFIP. It is presumed that in HFIP the M-helical as-
sembly is the thermodynamically preferred arrangement of
NCDP 1. Semiempirical quantum chemical and density
functional theory calculations on model structures were
used to examine the relative stabilities of M- and P-helical
assemblies, as discussed later.
Furthermore, we studied the effect of DMSO/HFIP sol-
vent composition on the chiral aggregation of NCDP 1. CD
spectra of NCDP 1 (500 mm) were recorded as a function of
increasing volume fraction of DMSO (v/v) in HFIP. There
was no change in the negative Cotton signal upon increasing
the volume fraction of DMSO up to 10% (v/v) in HFIP. Sur-
prisingly, however, the negative Cotton signal was trans-
formed completely to a bisignate positive Cotton signal at
volume fractions of DMSO>10% in HFIP, indicating a re-
versal of chiral assembly from M- to P-helicity (right-
handed). At 15% DMSO in HFIP (15:85, v/v), NCDP 1 ex-
hibited maximum CD signal in-
ACHTUNGTRENNUNGroisopropanol (HFIP), dimethyl sulfoxide (DMSO), and
mixtures thereof. Specifically, HFIP is known to stabilize
helical conformations in peptides through various mecha-
nisms.[26]
The high solvent polarity, hydrogen-bond accepting prop-
erties, and localized hydrophobic solvating effects of methyl
groups in DMSO are thought to facilitate solvatophobic in-
teractions, thereby inducing aggregation in binary solvent
mixtures through diverse mechanisms.[27] NCDP 1 (100 mm)
in HFIP showed absorption peaks in the region 300–400 nm,
a characteristic band I absorption for NDI. The correspond-
ing emission spectrum showed weak fluorescence character-
istic of amino acid-functionalized NDIs.[20,21] NCDP 1 exhib-
ited aggregation-induced self-assembly with increasing
volume fraction of DMSO (0–30%) in HFIP. A strong hy-
pochromic effect and a slight hypsochromic shift were ob-
served for the NDI absorption band (300–400 nm) (Fig-
ure 2a). CD studies were performed to gain insight into the
chiroptical properties of NCDP 1. In HFIP at lower concen-
trations (<100 mm), NCDP 1 did not show CD signals. How-
ever, a monosignate negative CD signal was obtained upon
tensity, with a red-shift in lmax
(CD signal position), suggesting
extended and more stable P-
helical assembly as opposed to
the initially formed M-helical
assembly in pure HFIP (Fig-
ure 2c). CD studies of NCDP
1 performed in DMSO alone
and in HFIP containing co-sol-
vents not isostructural with
DMSO under similar conditions
did not show any chiroptical
switching properties (Figures S1
and S6 in the Supporting Infor-
mation). Thus, DMSO in HFIP
is responsible for the observed
M- to P-helical inversion in the
chiral supramolecular assembly
of NCDP 1. We also carried out
CD measurements on NCDP
1 at 50 mm in both HFIP and
DMSO/HFIP (15:85, v/v) using
Figure 2. a) UV/Vis absorption spectra of NCDP 1 (100 mm) in HFIP with increasing volume fractions of
DMSO under ambient conditions, b) CD spectra of NCDP 1 in HFIP at increasing concentrations from 50 mm
to 500 mm, c) CD spectra of NCDP 1 (500 mm) in HFIP with increasing volume fractions of DMSO, d) CD
spectra of NCDP 1 in DMSO/HFIP (15:85, v/v) at concentrations from 50 mm to 500 mm; DMSO: dimethyl
sulfoxide; HFIP: 1,1,1,3,3,3-hexafluoropropan-2-ol. Arrow in c) indicates the chiroptical switching from M- to
P-helical assembly.
10 mm path length cuvettes to
rule out any absence of CD sig-
nals at low concentrations due
to insufficient sensitivity when
1 mm path length cuvettes were
Chem. Eur. J. 2013, 19, 16615 – 16624
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
16617

U. Deva Priyakumar, T. Govindaraju et al.
used. This CD study using 10 mm path length cuvettes did
not show any noteworthy additional signals, emphasizing the
significance of the minimum monomer concentration re-
quired for aggregation of NCDP 1 (Figure S5 in the Sup-
porting Information). To rule out linear dichroism (LD)-in-
duced artefacts in the observed helical assembly and chirop-
tical switching properties of NCDP 1, LD spectra were re-
corded under similar experimental conditions and showed
no significant signals (Figure S8 in the Supporting Informa-
tion). The observed chiroptical switching from monosignate
M-helical (in HFIP) to bisignate P-helical handedness in the
NCDP 1 assembly may be attributed to strong excitonic in-
teractions and preferential helical stabilization of this
system in DMSO/HFIP (15:85, v/v). It is proposed that the
DMSO molecules locally reorganize the HFIP solvent clus-
À
ters around the NCDP. The methyl groups ( CH3) of
DMSO can preferentially solvate NCDP 1 to induce a hydro-
phobic effect, which subsequently drives the inversion of the
M-helical to the thermodynamically more stable P-helical
assembly of NCDP 1 in DMSO/HFIP. Concentration-depen-
dent CD spectra were recorded in DMSO/HFIP (15:85, v/v)
to study the effect of monomer concentration on the ob-
served chiroptical switching of the helical assembly of
NCDP 1. The CD spectra of NCDP 1 from 100 to 500 mm in
Figure 3. Dynamic light-scattering (DLS) studies of NCDP 1 at 500 mm
(self-assembled chiral aggregates) in a) HFIP (37 nm), b) 5% DMSO in
HFIP (210 nm), c) 11% DMSO in HFIP (269 nm), and d) 15% DMSO
in HFIP (531 nm). Observed hydrodynamic size distributions are given in
parentheses.
DMSO/HFIP (15:85, v/v) showed
a
bisignate positive
nate CD signal, whereas the filtered solution did not show
any CD signal, as the centrifugation and filtration process
had removed the chiral aggregates (Figure S7 in the Sup-
porting Information). This study corroborated the observed
chirality and its origin through intermolecular self-assembly
of monomeric NCDP supramolecular synthons in solution.
Quantum chemical calculations were carried out to fur-
ther understand the magnitude of intermolecular interac-
tions in all of the NCDP molecules (1–6) in their M- and P-
helical supramolecular assembly states. Four dimer models
were constructed for the P- and M-helices for NCDPs 1–6
from their respective monomers. The differences between
the respective models lie in the conformational arrangement
of the monomer units. Since these molecules have long
linear side chains, several conformations are possible, of
which four straightforward possibilities were considered.
The interaction energies for all the models of the NCDP
1 molecule were calculated at the semiempirical PM7 and
density functional M06/6-31+G* levels of theory. The re-
sults obtained at these two levels of theory were in reason-
Cotton signal (P-helical bias) regardless of the concentration
(Figure 2d). This further emphasized the crucial role of the
DMSO/HFIP (15:85, v/v) solvent composition in stabilizing
the thermodynamically more stable P-helical assembly of
NCDP 1. Next, variable-temperature CD studies were car-
ried out to probe the effect of temperature on the chiropti-
cal switching and stability of the P-helical assembly. CD
spectra recorded for NCDP 1 (500 mm) in DMSO/HFIP
(15:85, v/v) between 25 and 608C showed no significant
changes in the sign or intensity of the CD signal during the
heating and cooling cycles. Thus, variable-temperature CD
study ruled out any influence of temperature on the ob-
served chiroptical switching and asserted the stability of
chiral aggregates at higher temperatures (data not shown).
The stability of P-helical aggregates of NCDP 1 can be at-
tributed to strong intermolecular aromatic p–p interactions
À
between the NDI cores supported by N H···O hydrogen
bonding between peripheral CDP auxiliaries.
Dynamic light-scattering (DLS) studies were carried out
to obtain direct evidence for the self-assembly of NCDP
1 in solution. DLS data for NCDP 1 at 500 mm in solution
showed the presence of aggregates, and the aggregate size
was found to vary with solvent composition (Figure 3). The
hydrodynamic sizes of the aggregates of NCDP 1 were
found to be 37 nm in HFIP, and 210, 269, and 531 nm in 5%
DMSO, 11% DMSO, and 15% DMSO in HFIP, respective-
ly. Furthermore, the observed chirality could be unequivo-
cally attributed to self-assembled NCDP 1 (500 mm) aggre-
gates in solution by recording CD spectra in DMSO/HFIP
(15:85, v/v) before and after centrifugation and filtration of
the solution through a 0.45 mm filter. The CD spectrum re-
corded from the as-prepared sample showed a strong bisig-
AHCTUNGTREGaNNNU ble agreement with each other (Table 1). The semiempiri-
cal PM7 method has been shown to reasonably capture non-
bonded interactions involving both electrostatic and disper-
sion interactions.[28] The interaction energies for NCDP 2
were also calculated at both the PM7 and M06 levels, and
were again found to be mutually consistent (data not
shown). Based on this, the other molecules were modelled
at the computationally less expensive PM7 level of theory.
The optimized geometries of the most stable M- and P-heli-
cal dimers for NCDP 1 are depicted in Figure 4. Molecular
models for the P- and M-helical supramolecular motifs for
NCDP 1 are shown in Figure 1. The interaction energies cor-
responding to the formation of such dimers were found to
16618
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 16615 – 16624

Chiroptical Switching in Naphthalenediimide-Based Biomimetics
FULL PAPER
Table 1. Relative energies (kcalmolÀ1) of the P- and M-helical models of
NCDP 1 dimers along with the interaction energies calculated at the
PM7 (Ia) and M06/6-31+G* (Ib) levels of theory.[a]
ute to the overall stability of the supramolecular assembly.
The intermolecular hydrogen bonding between the amide
groups of the constituent monomers of the corresponding
dimers was also verified by calculating second-order pertur-
bative interaction energies by means of natural bond orbital
(NBO) analysis at the ab initio HF level using the 6-31+G*
basis set. The interaction energies of the four amide groups
are given in Table S7 (see the Supporting Information).
From the data, it can be noted that there is strong intermo-
lecular hydrogen bonding between the amide groups of the
monomers. Explicit calculations involving the solvent mole-
cules are not practical to examine the role of the solvent in
the M- to P-helical transition.
However, based on the computational results and experi-
mental observations, possible determinants of the chiroptical
switching may be proposed, as discussed below. The twist
angles (helical twist between the two monomer units) calcu-
lated for the helical models were found to range between 35
and 408. The hydrogen bond distances between the amide
groups at either side of the monomer units were found to lie
in the range 1.75–1.95 ꢁ. P- and M-helical models of the
supramolecular assembly consisting of 24 monomer units
are presented in Figure 1. In these models, 12 monomers per
turn were included, with a distance of 3 ꢁ between any two
adjacent molecules.
Model Relative energy Interaction energy (Ia) Interaction energy (Ib)
I-P
0.0 (0.0)
À67.4
À52.0
À41.5
À35.4
À54.7
À49.2
À35.0
À27.2
À63.4
À45.8
À21.6
À21.1
À38.2
À30.2
À18.1
À9.3
II-P
III-P
IV-P
I-M
15.5 (17.6)
25.9 (41.8)
32.0 (42.4)
12.7 (25.2)
18.3 (33.3)
II-M
III-M 32.5 (45.3)
IV-M 40.3 (54.2)
[a] Relative energy values in parentheses correspond to calculations car-
ried out at the M06/6-31+G* level. Ia: Interaction energies calculated
using the energies of the optimized dimers and those of the optimized
monomer at the PM7 level. Ib: Interaction energies calculated using the
single-point energy of the optimized dimers and the single-point energy
of the optimized monomer at the M06/6-31+G* level (optimization at
the PM7 level). I to IV represent the dimers formed from four different
conformations considered for NCDP 1 (see Computational Details sec-
tion) in P- (right-handed) and M- (left-handed) helical arrangements, re-
spectively.
Next, we probed the effect of the a-substituent
À
À
À
(R= CH2C6H5, CH2CHACHTNUTRGNE(NUG CH3)2, H) in the CDP auxiliary
on the assembly properties of NCDPs. UV/Vis absorption
studies of NCDPs 2–4 revealed aggregation characteristics
similar to those of NCDP 1. With increasing volume fraction
of DMSO in HFIP, NCDPs 2–4 (100 mm) showed decreases
in absorbance and hypsochromic shifts in the region 300–
400 nm (Figures S9 and S10(a) in the Supporting Informa-
tion). NCDPs 2 and 3 (500 mm) showed monosignate nega-
tive CD signals in the region 300–400 nm in pure HFIP (M-
helical assembly). Similarly to NCDP 1, NCDPs 2 and 3
both showed chiroptical switching from a monosignate M-
helical Cotton signal to a bisignate P-helical Cotton signal
on increasing the volume fraction of DMSO in HFIP
(Figure 5). Notably, the solvent compositions (DMSO/HFIP,
v/v) giving the maximum positive Cotton signals were spe-
cifically different for NCDPs 1–3 (15:85, 30:70, and 40:60,
respectively) (Figure 2c, Figure 5). This variation in the sol-
vent composition of DMSO/HFIP may be necessary to
attain balanced polarity, hydrophobicity, and hydrogen-
bonding interactions to trigger chiroptical switching from
M- to P-helical assemblies of NCDPs 1–3 with different a-
substituents. In general, these results suggest that the chiral
assembly and chiroptical switching of NCDPs 1–3 is inde-
pendent of the nature of the bulky a-substituent (R) on the
second amino acid in the CDP auxiliary.
Figure 4. Optimized structures of a) P-helical dimer (I-P) and b) M-heli-
cal dimer (I-M) of NCDP 1.
be more favourable for the P-helices compared to the M-
helices. Interestingly, the CD intensity of a P-helix at
a given concentration of NCDP 1 in DMSO/HFIP was
found to be higher than that of an M-helix of NCDP 1 in
HFIP, indicating a higher stability of the former. Both the
P- and M-helices of NCDP 1 dimer involve hydrogen-bond-
ing interactions between the CDP amide groups. The hy-
droxyl groups of the tyrosine moieties in NCDP 1 are un-
likely to form hydrogen bonds between them as the distance
between the oxygen atoms of the two monomer units is
about 4 ꢁ. It should be noted that the P-helical models
were found to be thermodynamically more stable than the
M-helical assemblies. The stacking energy for the basic
naphthalenediimide stacked dimers was calculated to be
20 kcalmolÀ1 at the M06/6-31+G* level of theory. Compari-
son of the interaction energies given in Table 1 indicates
that the hydrogen-bonding interactions significantly contrib-
The remarkable chiroptical switching phenomenon further
encouraged us to investigate the effect of the chirality of the
second amino acid in the CDP auxiliaries. Initially, we ex-
amined the effect of an achiral amino acid (Gly) on the
chiral assembly and solvent-dependent chiroptical switching
property. NCDP 4 with cyclo(l-Lys-Gly) served as an effec-
Chem. Eur. J. 2013, 19, 16615 – 16624
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
16619

U. Deva Priyakumar, T. Govindaraju et al.
termolecular p–p stacking of the NDI chromophores and
hydrogen-bonding between the CDP units of NCDP, as evi-
denced by a downfield shift of the CDP amide proton sig-
nals accompanied by an upfield shift of the NDI chromo-
phore proton signals with increasing concentration (Fig-
ure S13 in the Supporting Information).[29]
Surprisingly, flat CD signals were observed for NCDP 4 at
all possible concentrations and solvent combinations of
DMSO/HFIP, indicating an absence of chiral bias or switch-
ing property in its supramolecular assembly (Figure S14 in
the Supporting Information). The absence of chiral bias and
chiroptical switching in NCDP 4 may be attributed to the
perfectly symmetrical nature of the resultant assembly. The
absence of a bulky a-substituent (R) and the chiral centre
on the second amino acid of the CDP auxiliary lead to insig-
nificant interconversion energy between the M- and P-heli-
cal assemblies. These results clearly emphasize the crucial
role of the chiral centre as well as the bulky a-substituent
on the second amino acid of the CDP auxiliary with regard
to the solvent-induced preferential helical bias and chiropti-
cal switching behaviour of NCDP supramolecular assem-
blies.
The origins of this distinct behaviour of NCPD 4 com-
pared to the other three NCDPs (1–3) discussed above were
examined by further quantum chemical calculations. The
average interaction energies for the four P- and M-type heli-
cal dimer models of the six NCDP molecules are represent-
ed in Figure 6. From the data, it is observed that for NCDPs
Figure 5. CD spectra of a) NCDP 2 and b) NCDP 3 in HFIP with increas-
ing volume fractions of DMSO at 500 mm. Grey arrows indicate the chi-
roptical switching from M- to P-helical assemblies.
tive control to study the transfer of chiral information from
a distant chiral centre on l-lysine to the NDI core as well as
to understand the influence of the second chiral centre on
the observed assembly properties of NCDPs 1–3. In contrast
to all the other NCDPs studied, NCDP 4 exhibited mirror-
image fluorescence emission in the region 380–450 nm in
HFIP (Figure S10(b) in the Supporting Information). The
monomeric emission band (380–450 nm) of NCDP 4 de-
creased with increasing volume fraction of DMSO in HFIP
and subsequently a new emission band at around 540 nm
was observed due to excimer-like aggregation.[24a] At a sol-
vent composition of DMSO/HFIP (20:80, v/v), complete
quenching of the monomeric emission band was observed,
accompanied by a colour change of the solution from violet
(monomeric emission) to yellow (excimer-like emission)
under UV light. To study the intermolecular hydrogen bond-
ing (CDP auxiliary) in NCDP 4, variable-temperature
1H NMR spectra were recorded. NCDP 4 showed upfield
shifts of the CDP amide signals at d=8.18 and 7.98 ppm to
d=7.91 and 7.72 ppm, respectively, on increasing the tem-
perature from 25 to 808C, which confirmed the hydrogen-
bonding network in its assembled structure (Figure S11 in
the Supporting Information). Similar upfield shifts of the
amide signals from d=8.05 and 8.01 ppm to d=7.78 and
7.67 ppm on increasing the temperature from 25 to 808C
were observed for NCDP 1 (Figure S12 in the Supporting
Figure 6. Average interaction energies for the P- and M-helical dimers
for all six molecules (NCDPs 1–6) calculated at the PM7 level of theory.
2 and 3, the P-helical dimer is thermodynamically more
stable than the M-helical dimer as in the case of NCDP 1.
The structures of the most stable P- and M-helical dimers at
the PM7 level of theory, along with the hydrogen bonds be-
tween the amide groups, are depicted in Figure S17 (see the
Supporting Information). The twist angles and the hydro-
gen-bonding distances between the cyclic dipeptide moieties
calculated for the other models were found to be similar to
those obtained for NCDP 1. Interaction energy calculations
on the dimers of NCDP 4 indicated comparable stabilities
for both the P- and M-forms (Figure 6). Visual inspection of
the modelled structures indicates that the P- and M-forms
of the supramolecular assembly of NCDP 4 are very similar
(Figure S17). Hence, molecules of NCDP 4 are likely to be
1
Information). Concentration-dependent H NMR spectra of
NCDP 1 in [D6]DMSO revealed the presence of strong in-
16620
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 16615 – 16624

Chiroptical Switching in Naphthalenediimide-Based Biomimetics
FULL PAPER
arranged almost equally in both forms, resulting in no CD
signal, as observed experimentally. The interaction energies
for all eight models for NCDPs 2, 3, and 4 are given in
detail in Tables S1–S6 (see the Supporting Information).
The intermolecular hydrogen-bonding interaction energies
for the most stable dimers of the above molecules are given
in Table S7 (see the Supporting Information).
spectrum of NCDP 1 (500 mm in HFIP) was recorded and
the solvent was removed in vacuo. The residue was redis-
solved in DMSO/HFIP (15:85, v/v) and the CD spectrum
was recorded to complete the first cycle. For the next cycle,
the mixed solvent (DMSO/HFIP) was removed in vacuo,
the residue was redissolved in HFIP, and the CD spectrum
was recorded. This procedure was followed over further
cycles and the full data is shown in Figure 7a. This study
We further investigated the effect of a change in chirality
of the second amino acid in the CDP auxiliary on the sol-
vent-dependent chiral assembly and chiroptical switching of
the NCDP aggregates. NCDPs 5 and 6 (epimers of NCDP
1 and 2) with d-Tyr and d-Phe, respectively, at 100 mm exhib-
ited a decrease in the absorbance intensity and a slight hyp-
sochromic shift with increasing volume fraction (v/v) of
DMSO in HFIP due to solvent-induced aggregation (Fig-
ure S15 in the Supporting Information). The CD spectra of
NCDPs 5 and 6 at 500 mm in HFIP showed flat CD signals
in the region 300–400 nm, indicating no specific helical bias
in their molecular assemblies. NCDPs 5 and 6 did not show
any significant spectral changes upon increasing the volume
fraction of DMSO (v/v) in HFIP, except that the flat CD sig-
nals in HFIP gradually became weak negative CD signals
(Figure S16 in the Supporting Information). The average in-
teraction energies for NCDPs 5 and 6 are given in Figure 6,
from which it is apparent that the M-helical dimer was mar-
ginally more stable than the P-helical dimer in both cases.
The helical angles and hydrogen-bonding distances were in
similar ranges to those of the other molecules. Energy-mini-
mized models for the M- and P-helical dimers of NCDPs 5
and 6 are given in Figure S17. Intermolecular hydrogen-
bonding interaction energies for the amides of the two
monoACHTUNGTRENNUNGmers (Table S7) are indicative of strong bonding be-
tween them, leading to dimers, in addition to p-stacking in-
teractions. NCDPs 5 and 6 with d-amino acids in the second
positions of their CDP auxiliaries did not display significant
CD signals due to mismatched chiral centres on the two
amino acids of the CDP auxiliary, resulting in irregular ag-
gregation. Thus, NCDPs 4–6 with no significant CD features
in HFIP did not exhibit chiroptical switching in the mixed
solvent (DMSO/HFIP). This confirmed that the a-substitu-
ent (R) and the chirality of the amino acid play essential
roles in the solvent-induced helical chirality and chiroptical
switching of the supramolecular assemblies of the NCDPs.
Therefore, the observed chiral aggregation of NCDPs 1–3 in
HFIP is due to the clustering and stabilization of M-type
helical assemblies, which is influenced by the a-substituent
and the chirality (l) of the amino acids in the CDP auxiliary.
The chiroptical switching behaviour of NCDPs 1–3 in
DMSO/HFIP can be attributed to an effective local contri-
bution of DMSO through the hydrophobic effect of its
methyl groups and possible hydrogen bonding as an accep-
Figure 7. Solution and drop-cast thin-film CD spectra of NCDP 1. a) CD
intensity plotted against each cycle of study for NCDP 1 at 500 mm in
^
^
HFIP ( l=380 nm) and DMSO/HFIP (15:85, v/v; l=385 nm), b) CD
spectra of NCDP 1 at 500 mm in solution (i: HFIP, ii: DMSO/HFIP
(15:85, v/v)) and drop-cast thin films (iii: from HFIP, iv: from DMSO/
HFIP (15:85, v/v)).
clearly demonstrated the reversibility of the solvent-induced
chiroptical switching, as reflected by the retention of the
CD features for NCDP 1 in HFIP (M-helicity) and DMSO/
HFIP (P-helicity) even after three cycles of solvent removal
and redissolution (Figure 7a). In addition, CD spectra were
recorded from thin films of NCDP 1 to further confirm the
observed solvent-induced reversible chiroptical switching.
Thin films were prepared by drop-casting NCDP 1 from so-
AHCTUNGTREGlNNUN utions in HFIP and DMSO/HFIP (15:85, v/v) onto quartz
substrates. The CD spectra of the thin films showed flat sig-
nals indicating no chiral bias in the solid state, which further
emphasized the crucial role of the solvent in the helical as-
sembly and reversible chiroptical switching of the NCDPs
(Figure 7b).
The intriguing solvent (DMSO/HFIP)-induced chiroptical
switching of self-assembled chiral aggregates of NCDPs
prompted us to further generalize this effect in other solvent
ACHTUNGTRENNUNGtor in reorganizing the HFIP clusters around the NCDP as-
sembly, among other bulk effects of the mixed solvent.[30]
Next, we investigated the reversibility of the chiroptical
switching property of NCDP 1 between M- and P-type heli-
cal assemblies by carrying out CD studies in HFIP and
DMSO/HFIP (15:85, v/v) in cycles. Specifically, the CD
Chem. Eur. J. 2013, 19, 16615 – 16624
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
16621

U. Deva Priyakumar, T. Govindaraju et al.
systems. Addition of solvents such as chloroform, dichloro-
methane, or 1-methyl-2-pyrrolidone failed to induce chirop-
tical switching of the M-helical aggregates of NCDP 1 in
HFIP. Next, we examined isostructural (ketone and alcohol)
solvents such as acetone, 2-pentanone, 3-pentanone, cyclo-
pentanone, and cyclohexanone, as they possess variable
linear or cyclic alkyl substituents on the C=O functionality
(Table 2), as well as 2-propanol (isopropanol). The CD spec-
of DMSO, the P-helical complexes were formed. It is pro-
posed that hydrogen-bond dynamics and hydrophobic ef-
fects within the supramolecular complex and with the sol-
vent play major roles in this chiral reversal. Based on quan-
tum chemical/DFT calculations and spectroscopic studies, it
has been proposed that the helix-stabilizing effect of specific
compositions of HFIP in peptides can be attributed to a clus-
tering and coating effect, entropic and enthalpic factors, and
variations in the kinetics of conformational changes.[26] It is
reasonable to postulate that similar effects are operative in
the initial stabilization of the M-helical assemblies of
NCDPs 1–3. It is possible that the amide groups (both C=O
Table 2. Molecular structures of various solvents that induce chiral
switching of M-helical aggregates of NCDP 1 (500 mm) in HFIP and %
volume fractions of each solvent in HFIP to achieve maximum positive
Cotton signal upon chiral inversion.
À
and N H) of NCDP in the less stable M-helix may form in-
Solvent
Solvent
structure
% Volume fraction of co-solvent in HFIP
(at maximum inversion)
termolecular hydrogen bonds, both with each other and with
the solvent cluster. In such a scenario, the energy difference
between the M- and P-helices will be compensated by the
hydrogen bonding with the solvent, as well as by entropic
and enthalpic factors. In the mixed solvent, the DMSO mol-
ecules reorganize the solvent cluster of HFIP through hy-
drogen bonding and localized hydrophobic effects, which
drive the switching from the initial M-type to the thermody-
namically more stable P-type helical assembly. Chiral rever-
sal is not observed in 5 and 6 since the energy differences
between the two states are calculated to be not so significant
(Figure 6). In these two cases, the marginally more stable
M-helical form is observed experimentally. Recently, Faul
et al.[4f] showed a similar effect in a symmetrical sugar-based
perylenediimide derivative, whereby a P-helical model was
thermodynamically more stable than the M-helix.
dimethyl sulf-
oxide
15
25
acetone
2-pentanone
3-pentanone
cyclopentanone
25
25
25
cyclohexanone
isopropanol
30
35
tra of NCDP 1 (500 mm) in HFIP with varying volume frac-
tions of the above mentioned solvents were recorded. Re-
markably, all of these solvents showed chiroptical switching
similar to that seen in the DMSO/HFIP system (Figures S2–
S4 in the Supporting Information). Interestingly, the volume
fractions required to obtain the maximum positive Cotton
signal upon chiral inversion varied with each solvent combi-
nation (25% acetone, 25% 2-pentanone, 25% 3-pentanone,
25% cyclopentanone, 30% cyclohexanone, and 35% isopro-
panol in HFIP). These results also revealed that the solvent
composition required to induce the maximum chiral inver-
sion was the same for all of the ketones (except cyclohexa-
none), that is, 25% in HFIP. Notably, isopropanol, the non-
fluorinated isostructural analogue of HFIP, exhibited a com-
pletely opposite effect by inducing chiroptical switching of
the M-helical assembly of NCDP 1 in HFIP to the thermo-
dynamically more stable P-helical assembly. This result may
have broader implications in understanding the distinct role
of fluorinated solvents compared to their non-fluorinated
analogues. Overall, the above CD data are in agreement
with the changes observed for NCDP 1 in DMSO/HFIP and
show the generality of the chiroptical switching phenomena
in HFIP containing solvents isostructural to DMSO (Fig-
Conclusion
In summary, symmetrical naphthalenediimides with CDP
chiral auxiliaries (NCDPs) have been designed and studied
to orchestrate preferential supramolecular helical assembly.
The contributions of intermolecular aromatic p-stacking and
hydrogen-bonding interactions have been established by var-
ious experimental studies and quantum chemical calcula-
tions. The solvent-dependent helical supramolecular assem-
bly and chiroptical switching (M- to P-type) of NCDP as-
semblies have been validated through a series of concentra-
tion-, solvent-, and temperature-dependent CD studies.
NCDPs 1–3 formed M-helical assemblies in HFIP, which un-
derwent chiral inversion to form thermodynamically more
stable P-helical assemblies in DMSO/HFIP mixtures. Fur-
ther CD studies revealed the significance of the a-substitu-
ent and the corresponding chirality of the peripheral amino
acid in the CDP auxiliary with regard to solvent-induced
helical assembly and the chiroptical switching properties of
the NCDPs. The characteristic chiroptical switching of the
helical assembly of NCDP is reversible and the system can
be reversibly transformed between M- and P-helices by
cycles of solvent removal and redissolution. Overall, the re-
markable helical assembly characteristics of the NCDPs re-
ported herein demonstrate the crucial role of the CDP
chiral auxiliary. We hope that the present study might in-
ACHTUNGTRENNUNG
namically more stable in the case of NCDPs 1–3, M-helical
supramolecular complexes were observed in the CD spec-
troscopic studies in HFIP. However, with gradual addition
16622
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 16615 – 16624

Chiroptical Switching in Naphthalenediimide-Based Biomimetics
FULL PAPER
spire the development of novel chiral auxiliaries to master
the art of preferential helical assembly of designed supra-
molecular synthons so as to obtain smart self-assembled sys-
tems and materials, as well as for chiroptical applications.
Further studies aimed at probing the roles of external stimu-
li in controlling the chiral molecular self-assembly are un-
derway in our laboratory.
[1] a) J. D. Watson, F. H. C. Crick, Nature 1953, 171, 737–738; b) L.
Pauling, R. B. Corey, H. R. Branson, Proc. Natl. Acad. Sci. USA
1951, 37, 205–211; c) J. E. Hein, D. G. Blackmond, Acc. Chem. Res.
2012, 45, 2045–2054.
[2] a) E. Yashima, K. Maeda, H. Iida, Y. Furusho, K. Nagai, Chem. Rev.
2009, 109, 6102–6211; b) B. L. Feringa, R. A. van Delden, N. Kou-
mura, E. M. Geertsema, Chem. Rev. 2000, 100, 1789–1816; c) J. W.
Canary, Chem. Soc. Rev. 2009, 38, 747–756.
[3] a) A. E. Rowan, R. J. M. Nolte, Angew. Chem. 1998, 110, 65–71;
Angew. Chem. Int. Ed. 1998, 37, 63–68; b) J. L. Serrano, T. Sierra,
Coord. Chem. Rev. 2003, 242, 73–85; c) M. A. Mateos-Timoneda,
M. Crego-Calama, D. N. Reinhoudt, Chem. Soc. Rev. 2004, 33, 363–
372; d) Y. Wang, J. Xu, Y. Wang, H. Chen, Chem. Soc. Rev. 2013, 42,
2930–2962.
[4] a) H. Engelkamp, S. Middelbeek, R. J. M. Nolte, Science 1999, 284,
785–788; b) H. Nakashima, M. Fujiki, J. R. Koe, M. Motonaga, J.
Am. Chem. Soc. 2001, 123, 1963–1969; c) A. Brizard, C. Aimꢂ, T.
Labrot, I. Huc, D. Berthier, F. Artzner, B. Desbat, R. Oda, J. Am.
Chem. Soc. 2007, 129, 3754–3762; d) J. Cui, A. Liu, Y. Guan, J.
Zhang, Z. Shen, X. Wan, Langmuir 2010, 26, 3615–3622; e) Y. W.
Huang, J. C. Hu, W. F. Kuang, Z. X. Wei, C. F. J. Faul, Chem.
Commun. 2011, 47, 5554–5556; f) J. C. Hu, W. F. Kuang, K. Deng,
W. J. Zou, Y. W. Huang, Z. X. Wei, C. F. J. Faul, Adv. Funct. Mater.
2012, 22, 4149–4158.
Experimental Section
General: Amino acids and coupling reagents were obtained from Nova-
biochem; other chemicals, solvents, and analytical grade reagents were
obtained from Sigma–Aldrich and were used as purchased without any
further purification. Elemental analysis was carried out on a Thermo Sci-
entific FLASH 2000 organic element analyzer. 1H and 13C NMR spectra
were acquired on a Bruker AV-400 spectrometer with chemical shifts re-
ported in parts per million (in CDCl3/[D6]DMSO/D2O, with tetramethyl-
silane as internal standard). Mass spectra were obtained on a Bruker Ul-
traflex II MALDI-TOF spectrometer. UV/Vis spectra and fluorescence
spectra were recorded on a Perkin–Elmer Lambda 900 spectrophotome-
ter and a Perkin–Elmer LS 55 spectrophotometer, respectively, using
1 mm quartz cuvettes at ambient temperature. Solution and thin-film cir-
cular dichroism (CD) and linear dichroism (LD) measurements were per-
formed on a JASCO J-815 spectropolarimeter under N2 atmosphere
using 1 mm path length quartz cuvettes unless otherwise mentioned and
the values are quoted in molar ellipticity, q (degcm2 dmolÀ1). Dynamic
light-scattering (DLS) measurements were carried out on a NanoZS anal-
[5] a) M. Fujiki, J. Am. Chem. Soc. 2000, 122, 3336–3343; b) M. Fujiki,
J. R. Koe, M. Motonaga, H. Nakashima, K. Terao, A. Teramato, J.
Am. Chem. Soc. 2001, 123, 6253–6261; c) A. P. H. J. Schenning, M.
Fransen, E. W. Meijer, Macromol. Rapid Commun. 2002, 23, 265–
270.
ACHTUNGTRENNUNGyser (Malvern, UK) under ambient conditions.
[6] S. Mayer, G. Maxein, R. Zentel, Macromolecules 1998, 31, 8522–
8525.
Computational details: The monomers for all six models under study
(NCDPs 1–6) were modelled using the GaussView 05 program.[31] The P-
and M-helical dimers were modelled from the initial monomer structure.
The P-helical dimers were modelled by placing the second monomer at
a distance of 3 ꢁ from the first monomer and then rotating the second
monomer in the anticlockwise direction by 308. The twist angle of 308
was chosen on the basis of the M06/6–31+G* optimization of the dimer
of naphthalenediimide. Similarly, the M-helical dimer was also modelled
in the same way by rotating the second monomer in the clockwise direc-
tion. The monomer and the two resultant dimers were then optimized at
the PM7 level of theory using the MOPAC 2012 program.[32] Based on
test calculations, we considered up to four different conformations for
each molecule under study. Furthermore, the optimized monomer and
the dimers of NCDPs 1 and 2 were further subjected to single-point
energy calculations at the M06 level[33] of theory using the 6–31+G*
basis set and the Gaussian 09 program.[34] The interaction energies were
calculated as the differences between the energies of the dimers and the
monomers. The donor–acceptor interactions between the individual mon-
omers resulting in the formation of the dimers were analysed for all of
the NCDP molecules under study using natural bond orbital (NBO) anal-
ysis carried out at the ab initio HF level of theory using the 6–31+G*
basis set. The NBO analysis was carried out using the NBO program
3.1[35] included in the G09 suite of programs.
[7] a) M. M. Green, C. Khatri, N. C. Peterson, J. Am. Chem. Soc. 1993,
115, 4941–4942; b) E. Yashima, K. Maeda, O. Sato, J. Am. Chem.
Soc. 2001, 123, 8159–8160; c) K. Sakajiri, T. Sugisaki, K. Moriya, S.
Kutsumizu, Org. Biomol. Chem. 2009, 7, 3757–3762.
[8] a) H. Goto, E. Yashima, Y. Okamoto, Chirality 2000, 12, 396–399;
b) T. Yamada, Y. Nagata, M. Suginome, Chem. Commun. 2010, 46,
4914–4916; c) Y. Nagata, T. Nishikawa, M. Suginome, Chem.
Commun. 2012, 48, 11193–11195; d) T. Qi, V. Maurizot, H. Noguchi,
T. Charoenraks, B. Kauffmann, M. Takafuji, H. Ihara, I. Huc, Chem.
Commun. 2012, 48, 6337–6339.
[9] A. Lohr, M. Lysetska, F. Wꢃrthner, Angew. Chem. 2005, 117, 5199–
5202; Angew. Chem. Int. Ed. 2005, 44, 5071–5074.
[10] K. Jyothish, M. Hariharan, D. Ramaiah, Chem. Eur. J. 2007, 13,
5944–5951.
[11] S. Cantekin, Y. Nakano, J. C. Everts, P. van der Schoot, E. W. Meijer,
A. R. A. Palmans, Chem. Commun. 2012, 48, 3803–3805.
[12] a) V. M. Guelev, M. T. Harting, R. S. Lokey, B. L. Iverson, Chem.
Biol. 2000, 7, 1–8; b) S. Guha, S. Saha, J. Am. Chem. Soc. 2010, 132,
17674–17677; c) G. G. Holman, M. Zewail-Foote, A. R. Smith,
K. A. Johnson, B. L. Iverson, Nat. Chem. 2011, 3, 875–881; d) G. W.
Collie, R. Promontorio, S. M. Hampel, M. Micco, S. Neidle, G. N.
Parkinson, J. Am. Chem. Soc. 2012, 134, 2723–2731; e) M. B. Avi-
nash, T. Govindaraju, Adv. Funct. Mater. 2011, 21, 3875–3882.
[13] a) S. Alp, S. Erten, C. Karapire, B. Koz, A. O. Doroshenko, S. Icli, J.
Photochem. Photobiol. A 2000, 135, 103–110; b) B. Erten, Y. Poso-
khov, S. Alp, S. Icli, Dyes Pigm. 2005, 64, 171–178.
Acknowledgements
[14] a) P. Pengo, G. D. Pantos, S. Otto, J. K. M. Sanders, J. Org. Chem.
2006, 71, 7063–7066; b) H. Shao, J. Seifert, N. C. Romano, M. Gao,
J. J. Helmus, C. P. Jaroniec, D. A. Modarelli, J. R. Parquette, Angew.
Chem. 2010, 122, 7854–7857; Angew. Chem. Int. Ed. 2010, 49, 7688–
7691.
[15] a) H. Shao, T. Nguyen, N. C. Romano, D. A. Modarelli, J. R. Par-
quette, J. Am. Chem. Soc. 2009, 131, 16374–16376; b) H. Shao, J. R.
Parquette, Chem. Commun. 2010, 46, 4285–4287; c) H. Shao, M.
Gao, S. H. Kim, C. P. Jaroniec, J. R. Parquette, Chem. Eur. J. 2011,
17, 12882–12885.
We thank Prof. C. N. R. Rao, FRS for constant support, JNCASR, De-
partment of Biotechnology (DBT)-Innovative Young Biotechnologist
Award (IYBA) and the Department of Science and Technology (DST),
India, for financial support. We also thank the CSIR, New Delhi, for
awarding a senior research fellowship to SM and the DST for awarding
an Inspire fellowship to VP.
Chem. Eur. J. 2013, 19, 16615 – 16624
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
16623

U. Deva Priyakumar, T. Govindaraju et al.
[16] W. S. Horne, N. Ashkenasy, M. R. Ghadiri, Chem. Eur. J. 2005, 11,
1137–1144.
[17] a) T. D. M. Bell, S. Yap, C. H. Jani, S. V. Bhosale, J. Hofkens, F. C.
De Schryver, S. J. Langford, K. P. Ghiggino, Chem. Asian J. 2009, 4,
1542–1550; b) M. M. Durban, P. D. Kazarinoff, C. K. Luscombe,
Macromolecules 2010, 43, 6348–6352.
[18] a) M. R. Molla, A. Das, S. Ghosh, Chem. Commun. 2011, 47, 8934–
8936; b) M. R. Molla, S. Ghosh, Chem. Eur. J. 2012, 18, 1290–1294.
[19] M. B. Avinash, T. Govindaraju, Adv. Mater. 2012, 24, 3905–3922.
[20] a) M. B. Avinash, T. Govindaraju, Nanoscale 2011, 3, 2536–2543;
b) M. B. Avinash, E. Verheggen, C. Schmuck, T. Govindaraju,
Angew. Chem. 2012, 124, 10470–10474; Angew. Chem. Int. Ed. 2012,
51, 10324–10328; c) M. B. Avinash, T. Govindaraju, J. Phys. Chem.
Lett. 2013, 4, 583–588.
[27] a) A. J. M. Kerrow, E. Buncel, P. M. Kazmaier, Can. J. Chem. 1995,
73, 1605–1615; b) B. R. Gayathri, J. R. Mannekutla, S. R. Inamdar,
J. Mol. Struct. 2008, 889, 383–393.
[28] J. J. Stewart, J. Mol. Model. 2013, 19, 1–32.
[29] In variable-temperature 1H NMR spectra of NCDP 1, the signal of
the peripheral phenolic protons showed an upfield shift from d=
9.11 ppm to d=8.84 ppm due to hydrogen bonding with solvent
molecules. Intermolecular hydrogen bonding is ruled out as the dis-
tance between the hydrogen-bonding acceptor sites will be >4.0 ꢁ,
as revealed by theoretical calculations and the energy-minimized as-
sembled structure.
[30] G. A. Hembury, V. V. Borovkov, Y. Inoue, Chem. Rev. 2008, 108, 1–
73.
[31] R. Dennington, T. Keith, J. Millam, Semichem Inc., Shawnee Mis-
sion KS, GaussView Version 5, 2009.
[32] J. J. P. Stewart, Stewart Computational Chemistry, Colorado Springs,
CO, USA, MOPAC2012, 2012, 151.
[21] M. Pandeeswar, M. B. Avinash, T. Govindaraju, Chem. Eur. J. 2012,
18, 4818–4822.
[22] a) J. C. MacDonald, G. M. Whitesides, Chem. Rev. 1994, 94, 2383–
2420; b) C. Prasad, Peptides 1995, 16, 151–164; c) K. R. C. Prakash,
Y. Tang, A. P. Kozikowski, J. L. Flippen-Anderson, S. M. Knoblach,
A. I. Faden, Bioorg. Med. Chem. 2002, 10, 3043–3048; d) M. B. Mar-
tins, I. Carvalho, Tetrahedron 2007, 63, 9923–9932.
[23] a) K. Hanabusa, Y. Matsumoto, T. Miki, T. Koyama, H. Shirai, J.
Chem. Soc. Chem. Commun. 1994, 1401–1402; b) R. J. Bergeron, O.
Phanstiel, G. W. Yao, S. Milstein, W. R. Weimar, J. Am. Chem. Soc.
1994, 116, 8479–8484.
[24] a) S. Manchineella, T. Govindaraju, RSC Adv. 2012, 2, 5539–5545;
b) T. Govindaraju, M. Pandeeswar, K. Jayaramulu, G. Jaipuria, H. S.
Atreya, Supramol. Chem. 2011, 23, 487–492; c) T. Govindaraju, Su-
pramol. Chem. 2011, 23, 759–767.
[25] a) T. J. Measey, K. B. Smith, S. M. Decatur, L. M. Zhao, G. L. Yang,
R. S. Stenner, J. Am. Chem. Soc. 2009, 131, 18218–18219; b) Z. Xie,
A. Zhang, L. Ye, Z. Feng, Soft Matter 2009, 5, 1474–1482.
[26] a) D. P. Hong, M. Hoshino, R. Kuboi, Y. Goto, J. Am. Chem. Soc.
1999, 121, 8427–8433; b) N. H. Andersen, R. B. Dyer, R. M. Fesin-
meyer, F. Gai, Z. H. Liu, J. W. Neidigh, H. Tong, J. Am. Chem. Soc.
1999, 121, 9879–9880; c) A. Jha, S. Narayan, J. B. Udgaonkar, G.
Krishnamoorthy, Biophys. J. 2012, 103, 797–806.
[33] Y. Zhao, D. G. Truhlar, Theor. Chem. Acc. 2008, 120, 215–241.
[34] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A.
Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A.
Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F.
Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M.
Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima,
Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr.,
J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N.
Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghava-
chari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N.
Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C.
Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J.
Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Mo-
rokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannen-
berg, S. Dapprich, A. D. Daniels, ꢄ. Farkas, J. B. Foresman, J. V.
Ortiz, J. Cioslowski, D. J. Fox, Gaussian 09, Revision C.01, Gaussian,
Inc., Wallingford CT, 2009.
[35] F. L. Weinhold, C. R. Lendis, Valency and Bonding: A Natural Bond
Orbital Donor–Acceptor Perspective, Cambridge University Press,
Cambridge, 2005.
Received: August 7, 2013
Published online: November 4, 2013
16624
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 16615 – 16624