Special Issue | October 2014 187
BARC NEWSLETTERFounder’s DaySTIMULI-RESPONSIVE CUCURBITURIL-ADORNED SUPRMOLECULAR MICELLAR ASSEMBLIES OF
CETYLPYRIDINIUM CHLORIDE
Jyotirmayee MohantyRadiation & Photochemistry Division
Abstract
The molecular recognition behavior of versatile macrocyclic receptors, cucurbiturils (CBs) have been investigated in
relation to their host-guest interaction with amphiphilic molecules, especially cationic surfactants having widespread
technological importance. Construction of novel cucurbituril (CB)-adorned supramolecular micellar assemblies
of a cationic surfactant, cetylpyridinium chloride (CPC), through noncovalent host-guest interactions has been
demonstrated. The distinct cation receptor features and cavity dimensions of the CB5 and CB7 homologues assert
that the macrocyclic hosts remain complexed with the CPC monomers and take part in the micelle formation with
a shift in cmc, a unique observation in contrast to that of classical host, b-cyclodextrin, and has been characterized
by photochemical, surface tension, conductivity, DOSY NMR and SANS measurements. The reversible response of
these soft supramolecular micellar structures to thermal-stimuli, which project their utility for on-demand smart
drug-delivery vehicles, has also been established.
Key Words: Host-guest interaction, cucurbiturils, surfactant, supramolecular-micellar assemblies, stimuli-
responsive
This Paper received the Samanta Chandra Sekhar Award 2011, at the Annual Meeting of the Odisha Bigyan Academy
Introduction
Supramolecular encapsulation of guest molecules
through macrocyclic hosts presents a convenient
pathway for modulation of molecular properties, as
it can introduce pronounced effects on the physico-
chemical properties of the included guest.1 Host-
guest interaction finds immense importance in
obtaining photostability, drug delivery, catalysis, and
sensor applications. Cucurbiturils (CBs), relatively new
addition to the repertoire of macrocyclic hosts, are
a unique class of water soluble macrocyclic receptor
molecules consisting of methylene bridged glycoluril
units (Chart 1).1,2 Structurally, the pumpkin-shaped
CBs constitute highly symmetrical hydrophobic cages
of low polarity and polarizability with two identical
dipolar portal ends comprised of carbonyl functional
groups.1,2 As a macrocyclic host, CBs have attracted
considerable attention in recent years owing to their
excellent binding abilities for varieties of guests.
Among different CBs, the homologue cucurbit[7]uril
(CB7, with 7 glycoluril units) forms stable inclusion
complexes with several guest molecules, like organic
dyes, protonated alkyl and aryl amines and cationic
dyes, via a combination of hydrophobic and ion-dipole
interactions.1-4 The lower homologue cucurbit[5]uril
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CONTENTS
188 Special Issue | October 2014
BARC NEWSLETTERFounder’s Day(CB5), having a smaller cavity size, interacts with metal
ions or forms exclusion complex with cationic organic
guests through its highly polarized carbonyl portals.2 In
this article, the supramolecular interactions of CB5 and
CB7 hosts with a cationic surfactant, cetylpyridinium
chloride, have been described in relation to the
modulation in the critical micelle concentration (cmc),
temperature-responsive tunability and their potential
applications.
concentrations, the cmc gradually increases from its
normal value of 1 mM to 1.63 mM in the presence of
2 mM CB7 (Fig.1 a-c). In contrast, the titration of NR
with CPC in the presence of CB5 (1 mM), displayed a
downward shift in the cmc (0.57mM) (Fig.1 d, e).5 The
shift in cmc of CPC in the presence of CB5/CB7 was
also confirmed by surface tension and conductivity
measurements.
Chart 1: Chemical structures of the cucurbituril hosts and CPC surfactant.
Cucurbituril-adorned Suprmolecular Micellar Assemblies
Cetylpyridinium chloride (CPC, Chart 1) belongs to
a class of frequently used cationic surfactants and
exhibits intriguing microstructural changes with
anionic additives such as hydrotropes, electrolytes, bile
salts, etc. Owing to its vast applications, we attempted
to explore its intriguing assembly features in the
presence of supramolecular host, CBs, to have control
for an on demand uptake and release.
In the photochemical approach, we employ a
fluorescent probe, Nile Red (NR), which shows
characteristic changes in its spectral properties due
to its preferential positioning in the interfacial region
of the micelle. As shown in Fig. 1, the micellization
behavior was examined in the presence of the
macrocyclic host, CB7 and CB5. With increasing CB7
Fig.1: Fluorescence titration curves of NR (~2 mM) with different concentrations of CPC in the absence and presence of CB hosts: absence of CBs (a); 1.5 mM CB7 (b); 2.0 mM CB7 (c); and 0.5 mM CB5 (d); 1 mM CB5 (e). lex = 550 nm, lmon = 660 nm.
Considering the dimensions of the CB portals (portal
diameter ~5.4 Å and ~2.4 Å for CB7 and CB5,
respectively),2 and CPC (width of pyridinium group
<5 Å and length of hydrocarbon chain ~17 Å), it is
apparent that the pyridinium group of CPC can be
accommodated within the CB7 cavity. CPC cannot
be accommodated inside the CB5 cavity, however, an
exclusion complex based on ion-dipole interactions
is possible. Earlier studies using cyclodextrin (CD)/
CB7 hosts and other surfactant molecules have
suggested that the reduction in the surfactant-
monomer concentration is the prevailing mechanism
for the upward cmc shift where the host-bound
surfactant monomers do not participate in the micelle
formation.6,7 However, a similar mechanism in the
present case cannot explain the contrasting cmc shifts
observed with the CB7 and CB5 hosts, which points to
possible participation of the CB-bound CPC monomers
in the micelle formation.
Special Issue | October 2014 189
BARC NEWSLETTERFounder’s DayThe participation of the CB hosts in the micelle
structure has also been confirmed by DOSY NMR
measurements. If the cucurbiturils remain attached to
the CPC as inclusion or exclusion (in the vicinity of the
CPC head group) complexes, the diffusion coefficients
of both the CPC protons as well as the CB7 protons
would get affected on micellization. The average
diffusion coefficient of the –CH protons of CPC in the
presence of CB5 or CB7, decreases with increasing
CPC concentrations. While the diffusion coefficient
of CB5 protons remain unchanged, CB7 protons
show a gradual decrease even beyond the cmc (Fig.
2), indicating that the CB7-CPC unit is incorporated
within the micellar assembly. However, similar studies
with b-cyclodextrin (bCD) displayed such changes after
an initial slight decrease, which was expected for its
involvement with the monomers.5
Fig.2: Plot of the diffusion coefficient values for the b-CD (a), CB7 (b) and the CB5 (c) protons with CPC concentration.
significant decrease in the surface charge on the
micelle (0.17 to 0.10). This is very much in line with
the existence of CB7 beaded CPC micelle. On the
other hand, in the CB5-CPC system, though the SANS
data indicated a significant reduction in the surface
charge, the micellar dimensions remained unchanged,
suggesting an externally embedded CB5 on the CPC
micelle. Based on the above results, the positioning of
the CB7/CB5 hosts in the CPC micelle can be visualized
as in Fig. 3. In the case of CB5, the macrocycle remains
in the periphery of the micellar structure, whereas in
the case of CB7, the CB7-CPC complex is incorporated
within the micellar structure leading to the formation
of mixed micelles. The incorporation of CB7 at the
neck of the pyridinium head group provides optimum
interaction for the negatively polarized CB portals with
the cationic charge of the pyridinium head group. In
addition a part of the alkyl chain is included in the
cavity of the macrocycle due to favorable hydrophobic
interactions. The partial encapsulation of alkyl chain of
CPC within the CB7 host can reduce the hydrophobicity
of the alkyl chain and can lead to an increase in the
cmc.5
Stimuli-responsive Tuning
The advantages of the contrasting supra-molecular cmc
shift established in CPC on using CB7 or CB5 has been
explored further to demonstrate a supramolecularly
tunable cmc, which has implications in drug transport,
binding and release strategy, etc. The effect of
increasing CB7 concentration or solution temperature
on the cmc of CPC in a solution containing 1 mM
Fig.3: Schematic representation of the distinct cucurbituril adorned micellar assemblies formed by CPC (a), in presence of CB7 (b), and CB5 (c).
Small-angle neutron scattering
(SANS) measurements on the
CB7-CPC system revealed that
the micellar structure of CPC is
prolate ellipsoidal with axes 34.3
Å (a) and 18.5 Å (b). However,
in the presence of CB7, there is
slight elongation along the major
axis from 34.3 to 35.9 Å with a
190 Special Issue | October 2014
BARC NEWSLETTERFounder’s DayCB5 has been investigated. The fluorescence titration
curves progressively shifted with the addition of CB7
or increasing temperature and the corresponding cmc
values demonstrated a tunable range from 0.57 to
1.6 mM (Fig. 4).5 The addition of CB7 or increase in
temperature at the above discussed conditions disrupts
the CB5-CPC micellar structure, which establishes a
facile host/temperature-induced release mechanism
having direct relevance in drug delivery applications.
demonstrates a continuous tunable range for the
micellization of CPC. The supramolecular modulation
of the surfactant aggregates, envisioned in the present
work is very potent and promising for pharmacological
applications and for designing tunable artificial
molecular devices or nanoreactors.
Acknowledgements
I acknowledge all my collaborators and co-authors of
our published works. I also thank the colleagues in
RPCD and CG, BARC for their constant encouragement
and support.
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Fig. 4: Micellization curve for the CB5 or CB7 adorned CPC surfactant and the proposed release mechanism for the CB5 assembly.
Conclusion
The established cucurbituril-adorned, thermo-
responsive on/off supramolecular micellar assemblies
of the cationic surfactant, CPC, is schematically shown
in figure 4. While the supramolecular additive, CB5,
exhibits an early micellization of CPC at ~0.57 mM,
the CB7 host delays the same to about 1.6 mM of
CPC. Response of these systems to external stimuli,
such as, temperature or the combination of CB5/CB7,