Cucurbit[7]uril: Surfactant host-guest complexes in equilibrium with micellar aggregates

Article abstract of DOI:10.1002/cphc.201001045

In order to compare the formation of host-guest complexes between β-cyclodextrin (β-CD) or cucurbit[7]uril (CB7) and cationic surfactants we studied the hydrolysis of 4-methoxybenzenesulfonyl chloride (MBSC). The selected surfactants allowed the length of

Full text of DOI:10.1002/cphc.201001045

DOI: 10.1002/cphc.201001045
Cucurbit[7]uril: Surfactant Host–Guest Complexes in
Equilibrium with Micellar Aggregates
Marcia PessÞgo,[a, b] Nuno Basilio,[a] Jose A. Moreira,[b] and Luis Garcꢀa-Rꢀo*[a]
In order to compare the formation of host–guest complexes
between b-cyclodextrin (b-CD) or cucurbit[7]uril (CB7) and cat-
ionic surfactants we studied the hydrolysis of 4-methoxyben-
zenesulfonyl chloride (MBSC). The selected surfactants allowed
the length of the hydrocarbon chain to be varied between 6
and 18 carbon atoms. Contrary to the expected behaviour, the
values of the binding constants between CB7 and surfactants
are independent of the alkyl chain length of the surfactant. In
the case of b-CD, however, a clear dependence of the binding
constant on the hydrophobic character of the surfactant was
observed. The values obtained with CB7 are significantly
higher than those obtained with b-CD and these differences
are explained to be a consequence of electrostatic interactions
of the surfactants with the portals of CB7. It was found that a
small percentage of uncomplexed CB7 was in equilibrium with
the cationic micelles and this percentage increased on increas-
ing the hydrophobic character of the surfactant.
1. Introduction
Studies of host–guest interactions often provide fundamental
insights into supramolecular chemistry.[1,2] Cyclodextrins
(CDs)[3,4] and cucurbiturils (CBn)[5–7] are both important host
molecules that have been extensively studied and character-
ized in condensed media. Cyclodextrins are cyclic oligosaccha-
rides composed of glucose units. The best characterized forms
are a-, b- and g-CD and these consist of six, seven and eight d-
glucose units, respectively. The CD structure provides an exter-
nal hydrophilic region, where primary and secondary OH
groups are located, as well as a relatively hydrophobic cavity.
Therefore, CD hosts can form inclusion complexes with guest
molecules of appropriate size, shape and polarity.[3] In contrast
to the host–guest chemistry of a-, b- and g-CDs, which has de-
veloped steadily over the past century, the supramolecular
chemistry of cucurbit[6]uril, CB6, only began to develop in the
1980s and 1990s as a result of the pioneering work of Mock,[8]
Buschmann and co-workers[9] and Kim and co-workers.[10,11] In-
terest in the CBn family has increased dramatically in the new
millennium following the preparation of four new CBn homo-
logues (CB5, CB7, CB8 and CB10.CB5) by the research groups
of Kim and Day.[7,12,13] Cucurbiturils are pumpkin-shaped cavi-
ties composed of n glycoril units linked by a pair of methylene
groups.[6,7,10,11] The two identical carbonyl-fringed portals have
a considerable negative charge density, which facilitates the
binding of metal ions and cationic organic compounds, while
the inner cavities are relatively hydrophobic and can host neu-
tral molecules that fit within.[14–21] The cavity sizes of CB7 and
CB8 are comparable to those of b- and g-CD, respectively, and
they exhibit extraordinary host–guest properties[5,6,10,11,22–25]
that are distinctly different from those of the cyclodextrins.
Despite extensive studies on the host–guest chemistry of
CBn, little attention has been paid to the interaction of CBn
with amphiphilic molecules that contain a long alkyl chain. In
the literature there are a few previous studies on the complex-
ation of cationic[26,27] or nonionic[28] surfactants with CBn, but
none of these studies covers the postmicellar region. Mixed cy-
clodextrin–surfactant systems have been widely studied due to
their numerous applications in commercial formulations[29,30]
and the capacity of cyclodextrins to modulate the physico-
chemical properties of micellar solutions. These systems offer
the possibility to systematically study the association process,
because the properties of micellar solutions can be modulated
in a controlled manner by varying the surfactant structure. As
a consequence of the binding process some properties of the
target molecules can change dramatically [e.g. the critical mi-
celle concentration (cmc)]. The presence of CDs in solutions of
amphiphiles that form micelles or other types of self-assem-
bled aggregates introduces
a new equilibrium into the
medium and this may lead to the dissolution of the self-assem-
bled aggregates.[31,32] Inclusion complexes have been charac-
terized by a wide variety of techniques such as conduc-
tance,[33,34] speed of sound,[35,36] NMR,[33] fluorescence,[37] surfac-
tant selective electrode,[38,39] surface tension[40] and kinetic
methods[41–43] among others.
[a] M. PessÞgo, N. Basilio, Prof. L. Garcꢀa-Rꢀo
Departamento de Quꢀmica Fꢀsica y Centro Singular de Investigaciꢁn en
Quꢀmica Biolꢁgica y Materiales Moleculares
Universidad de Santiago
15782 Santiago (Spain)
Fax: (+34)981595012
E-mail: luis.garcia@usc.es
[b] M. PessÞgo, Dr. J. A. Moreira
CIQA, Departamento de Quꢀmica, Bioquꢀmica e Farmꢂcia
Faculdade de CiÞncias e Tecnologia
Universidade do Algarve
Campus das Gambelas, 8005-139 Faro (Portugal)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cphc.201001045.
1342
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemPhysChem 2011, 12, 1342 – 1350

Surfactant Host–Guest Complexes in Equilibrium with Micellar Aggregates
Herein we present a systematic study of mixed systems of
trimethylalkylammonium surfactants [(CH3)3N+CnTA, CnTA+, n=
6–18] and CB7. In studying these systems we used the hydroly-
sis of 4-methoxybenzenesulfonyl chloride (MBSC) as a chemical
probe. MBSC is a molecule the geometry and polarity of which
are suitable for complex formation with CB7. Published work
on the solvolysis of MBSC shows that the reaction is highly sus-
ceptible to changes in the polarity of the medium.[44–46]
Experimental Section
The surfactants and MBSC were supplied by Aldrich in the highest
available purity and were used without further purification. Cucur-
bit[7]uril was synthesized as described in our previous paper.[47]
Solutions of MBSC were prepared in acetonitrile due to the low
Figure 1. Influence of CB7 on the pseudo-first-order rate constant, kobs, for
the hydrolysis of MBSC at 258C.
solubility of this compound in water. The fraction of acetonitrile in
the reaction mixtures was always 1% (v/v). Surfactant–CB7 systems
were prepared by mixing appropriate volumes of stock aqueous
solutions of CB7 and the surfactant. Kinetic runs were initiated by
injection of a stock solution of MBSC into the mixed system in a
1 cm cuvette.
The reaction kinetics were monitored by UV-Vis at 270 nm (the ab-
sorption maximum of MBSC) in a Cary UV-Vis spectrophotometer
thermostated at 25.0ꢀ0.18C. In all cases the MBSC concentration
was 1.0ꢂ10ꢁ4 m. The absorbance-time data for all kinetic experi-
ments were fitted to a first-order integrated equation, and the
values of the pseudo-first-order rate constants, kobs, were reprodu-
cible to within 3%. The critical micelle concentration (cmc) of the
mixed systems was obtained kinetically and in the case of C18TACl
by calorimetric measurements. The binding constants for the inclu-
sion complex of CnTA+ with CB7 were determined by isothermal ti-
tration calorimetry using a VP-ITC instrument from MicroCal. The
binding constant calculations were performed with Origin 7.0,
which is part of the MicroCal VP-ITC software suite.
Scheme 1.
kw þ kCB7KCB7½CB7ꢂ
ð1Þ
kobs
¼
1 þ KCB7½CB7ꢂ
where KCB7 is the equilibrium binding constant of the substrate
to CB7, kCB7 is the rate constant for the reaction in the cavity of
CB7 and kw is the rate constant for hydrolysis in the aqueous
medium. Equation (1) gave an excellent fit to the experimental
data (Figure 1) from which the parameters kw =(6.44ꢀ0.01)ꢂ
2. Results and Discussion
The aim of the work described here was to study the differen-
ces in the formation of host–guest complexes between cation-
ic surfactants and b-cyclodextrin or cucurbit[7]uril. In order to
study these systems the hydrolysis of MBSC was used as a
chemical probe. The geometry and polarity of this compound
are suitable for complex formation with b-CB or CB7.
10ꢁ3 sꢁ1,
K
CB7 =(1.8ꢀ0.1)ꢂ104 mꢁ1 and
k
CB7 =(6.2ꢀ0.1)ꢂ
10ꢁ5 sꢁ1 were obtained. The kCB7 value is clearly lower than the
value obtained in bulk water but is similar to that obtained in
90% ethanol, k90%EtOH =5.99ꢂ10ꢁ5 sꢁ1.[45] This behaviour is com-
patible with that previously found for the solvolysis of substi-
tuted benzoyl chlorides in the cavity of CB7.[47]
2.1. Solvolysis of MBSC in the Presence of CB7
The influence of CB7 on the rate constant for solvolysis of
MBSC was studied. The influence of the CB7 concentration on
the observed rate constant is shown in Figure 1 and it can be
seen that the addition of CB7 to the reaction medium inhibits
the hydrolysis of MBSC. The observed inhibition is attributed
to the formation of an inclusion complex (MBSC–CB7) between
MBSC and CB7, as shown in Scheme 1.
2.2. Solvolysis of MBSC in the Presence of Cationic Micelles
The influence of surfactant concentration on the solvolytic rate
constant was studied over a wide range of surfactant concen-
trations that included the region before the cmc, where the
molecules of the surfactants are like monomers dispersed in
the solution, and the region after the cmc, where the surfac-
tant molecules are associated to form micelles. The effect of
the surfactant concentration, C18TACl as an example, on the
pseudo-first-order rate constant, kobs, for the hydrolysis of
The kinetic scheme considers that the solvolytic reaction
takes place in two well-differentiated environments: water, kw,
and the CB7 cavity, kCB7. The following rate equation can be
obtained from Scheme 1 [Eq. (1)]:
ChemPhysChem 2011, 12, 1342 – 1350
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemphyschem.org
1343

L. Garcꢀa-Rꢀo et al.
solvolysis of MBSC. Two well-differentiated environments were
considered: water and a micellar pseudophase between which
MBSC is distributed (Scheme 2).
Scheme 2.
Figure 2. Influence of C18TACl concentration on the pseudo-first-order rate
constant, kobs, for the hydrolysis of MBSC at 258C.
By considering simultaneous reactions in both bulk water
and the micellar pseudophase, the following expression can be
obtained for kobs [Eq. (2)]:
MBSC is shown in Figure 2. As can be seen, the observed rate
constant remains practically unchanged on increasing the sur-
factant concentration up to the cmc. At concentrations above
the cmc a clear decrease in kobs can be seen. At this point the
surfactant forms micellar aggregates and the substrate is incor-
porated into the micelles, a situation that explains why the
rate of the solvolytic reaction is lower than that in bulk water.
The cmc values were also determined by calorimetric meas-
urements (as an example, the determination for C18TACl is rep-
resented in Figure 3). As can be seen (Figure 3c), the minimum
in the first derivative of the integrated heat corresponds to the
C18TACl cmc value of cmcꢃ3ꢂ10ꢁ4 m and this is identical to
the value obtained kinetically, cmc=3.02ꢂ10ꢁ4 m.
kw þ kmKm½Dnꢂ
ð2Þ
kobs
¼
1 þ Km½Dnꢂ
where Km is the distribution constant of MBSC between the
water and the micellar pseudophases, [Dn] is the concentration
of micellized surfactant ([Dn]=[Surfactant]Tꢁcmc) and km is the
rate constant in the micellar pseudophase. The critical micelle
concentration values are required to fit the experimental re-
sults to Equation (2) and these values can be obtained kineti-
cally as the minimal surfactant concentration necessary to ob-
serve an appreciable change in kobs. Fitting the experimental
results to Equation (2) allowed us to obtain the parameters
listed in Table 1.
The micellar pseudophase formalism was applied to obtain
a quantitative interpretation of the experimental results for the
2.3. Solvolysis of MBSC in the
Presence of CB7–Surfactant
Mixed Systems
The effect of cationic micelles on
the solvolysis of MBSC contain-
ing CB7 was assessed by carry-
ing out experiments at a con-
stant CB7 concentration (7ꢂ
10ꢁ4 m) and varying the surfac-
tant concentration from values
clearly lower than the cmc to
values beyond the micellization
point. As an example, the results
obtained for C12TABr and C18TACl
in the presence of CB7 are
shown in Figure 4.
2.3.1. Qualitative Explanation
It can be observed from Figure 4
that the value of the rate con-
Figure 3. Titration of 158 mL of C18TACl micelles (6 mm) into 1.459 mL of water in 40 steps at 258C. a) Calorimetric
traces (heat flow against time). b) Enthalpy process versus [C18TACl] in the cell. c) First derivative of curve b calcu-
lated numerically from interpolated values.
stant, kobs, extrapolated to zero
surfactant concentration is in
1344
www.chemphyschem.org
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemPhysChem 2011, 12, 1342 – 1350

Surfactant Host–Guest Complexes in Equilibrium with Micellar Aggregates
kobs is independent of the surfactant concentration. This is be-
Table 1. Critical micelle concentrations obtained experimentally and the
parameters of Equation (2) for the hydrolysis of MBSC in the presence of
surfactant.
cause the cmc increases as the alkyl chain length decreases.
2.3.2. Binding Constants of CnTA+ to CB7 and Comparison
Surfactant
cmc [m]
k
m [sꢁ1
]
Km [mꢁ1
]
6.04ꢂ10ꢁ2
1.09ꢂ10ꢁ2
3.00ꢂ10ꢁ3
1.00ꢂ10ꢁ3
3.02ꢂ10ꢁ4
(8.7ꢀ0.1)ꢂ10ꢁ5
(1.4ꢀ0.3)ꢂ10ꢁ4
(1.3ꢀ0.7)ꢂ10ꢁ4
(1.0ꢀ0.9)ꢂ10ꢁ4
(1.6ꢀ0.4)ꢂ10ꢁ4
92ꢀ9
273ꢀ24
292ꢀ17
471ꢀ27
678ꢀ25
with b-CD
C10TABr
C12TABr
C14TABr
C16TACl
C18TACl
The binding constants between CB7 and each surfactant, Ks,
were studied by calorimetric measurements. As an example,
the results obtained in the case of C10TABr are shown in
Figure 5. The binding isotherm data were fitted to a theoretical
curve “one set of sites” supplied by MicroCal, with K, DH and
DS as adjustable parameters. The values of the binding con-
stants of CnTA+ to CB7 are listed in Table 2.
agreement with the values obtained in the absence of surfac-
tant (Figure 1). When the CB7 concentration was kept con-
stant, the value of kobs increased to a maximum as the concen-
tration of surfactant increased. This change is due to the com-
petitive formation of an inclusion complex between CB7 and
the surfactant. The formation of this complex displaces MBSC
toward the aqueous medium where the rate constant is
higher. The competitive formation of the CB7–surfactant inclu-
sion complex occurs until the concentration of surfactant mon-
omers reaches the value at which the micellization process
begins. When the micelles are formed an inhibitory effect is
observed because MBSC is incorporated into the micelles.
Therefore, the minimal surfactant concentration necessary to
observe an appreciable change in the maximum of kobs is at-
tributed to the micellization point.
It can be seen from Figure 6 that there is a relationship be-
tween Ks and the chain length of the surfactants in the com-
plexation by b-CD. The hydrophobic character of the surfac-
tants increases on increasing the alkyl chain length and thus,
the affinity to bind with b-CD also increases. Contrary to the
expected behaviour, in the case of CB7 the values of the bind-
ing constants between CB7 and surfactants, Ks, are essentially
independent of the increasing length of the hydrocarbon
chain of the surfactant. As an example, the Ks value for C14TABr
and CB7 of Ks =(2.6ꢀ0.9)ꢂ106 mꢁ1 is significantly higher than
that for b-CD,[43] Ks =(49.5ꢀ0.5)ꢂ103 mꢁ1, and this difference
can be explained by electrostatic effects. Electrostatic effects
can play a crucial role in molecular recognition events in both
aqueous and organic solutions.[48] The electrostatic potential at
the portal and within the cavity of CB7 is significantly more
As can be seen in Figure 4, as the alkyl chain length of the
surfactant decreases one can observe a limiting value at which
~
*
Figure 4. Influence of surfactant concentration on the observed rate constant for the solvolysis of MBSC in the presence of CB7. C18TACl ( ) and C12TABr ( ).
ChemPhysChem 2011, 12, 1342 – 1350
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemphyschem.org
1345

L. Garcꢀa-Rꢀo et al.
Figure 6. Values of the binding constants for each surfactant obtained by
calorimetric measurements.
2.3.3. Influence of the Presence of CB7 on the Critical Micelle
Concentration
In the presence of CB7 the maximum in the curve kobs versus
[Surfactant] is displaced to higher surfactant concentrations.
This effect is due to complexation of the surfactant monomers
with CB7 and the consequent effect on the cmc. For example,
in the case of C18TACl the addition of CB7, [CB7]=7ꢂ10ꢁ4 m,
produces an increase in the cmc from 3.02ꢂ10ꢁ4 m in the ab-
sence of CB7 to 1.14ꢂ10ꢁ3 m in the presence of 7ꢂ10ꢁ4 m of
CB7. For this surfactant the cmc values were also determined
by calorimetric measurements (Figures 3,7). As can be seen, in
the absence of CB7 (Figure 3c) the minimum of the curve cor-
responds to the value of the C18TACl cmc, cmcꢃ3ꢂ10ꢁ4 m,
and this value is identical to that obtained kinetically (cmc=
3.02ꢂ10ꢁ4 m). In the presence of CB7 (Figure 7c) the curve
shows a maximum and a minimum. The maximum is related
to the point at which the complexation capacity of CB7 is satu-
rated and the minimum indicates the minimum concentration
of surfactant at which the micellization process begins. In the
presence of CB7 calorimetric measurements gave a cmc value
of ꢃ1ꢂ10ꢁ3 m and this value is comparable to that obtained
kinetically, cmc=1.14ꢂ10ꢁ3 m.
Figure 5. Titration of 158 mL of C10TABr (2.5 mm) into 1.459 mL of CB7
(0.09 mm) in 40 steps at 258C. a) Calorimetric traces (heat flow against time).
b) Binding isotherms (obtained by integrating the peaks of the upper curve)
versus molar ratio.
negative than that for b-CD. This difference in electrostatic po-
tential has significant consequences for their recognition be-
haviour: CB7 exhibits a pronounced preference to interact with
cationic guests whereas b-CD prefers to bind to neutral or
anionic guests.[6]
CB7 has two identical carbonyl-fringed portals that have a
considerable negative charge density which facilitates the
binding of cationic organic compounds, whereas the inner cav-
ities are relatively hydrophobic and can host neutral molecules
that fit within. The ammonium group of the guest is located
just outside the portal, while the hydrocarbon chain is inside
the CB7 cavity.
2.3.4. Is there any Interaction between CB7 and Cationic
Micelles?
In the presence of CB7 at surfactant concentrations higher
than the cmc we can consider two types of interaction: CB7 is
Table 2. Compilation of kinetic parameters obtained for the solvolysis of MBSC in CB7–surfactant mixed systems.
Surfactant
cmcapp [m]
kw [sꢁ1
]
km [sꢁ1
]
Km [mꢁ1
]
kCB7 [sꢁ1
]
KCB7 [mꢁ1
]
Ks [mꢁ1
]
C6TABr
C8TABr
C10TABr
C12TABr
C14TABr
C16TACl
C18TACl
–
–
(6.44ꢀ0.01)ꢂ10ꢁ3
(6.44ꢀ0.01)ꢂ10ꢁ3
(6.44ꢀ0.01)ꢂ10ꢁ3
(6.44ꢀ0.01)ꢂ10ꢁ3
(6.44ꢀ0.01)ꢂ10ꢁ3
(6.44ꢀ0.01)ꢂ10ꢁ3
(6.44ꢀ0.01)ꢂ10ꢁ3
–
–
–
–
(7.1ꢀ0.3)ꢂ10ꢁ5
(6.5ꢀ0.1)ꢂ10ꢁ5
(9.6ꢀ0.2)ꢂ10ꢁ5
(1.3ꢀ0.3)ꢂ10ꢁ4
(9.7ꢀ0.6)ꢂ10ꢁ5
(6.5ꢀ0.3)ꢂ10ꢁ5
(9.7ꢀ0.1)ꢂ10ꢁ5
(1.6ꢀ0.3)ꢂ104
(1.8ꢀ0.1)ꢂ104
(1.8ꢀ0.1)ꢂ104
(1.8ꢀ0.3)ꢂ104
(1.8ꢀ0.1)ꢂ104
(1.8ꢀ0.1)ꢂ104
(1.6ꢀ0.2)ꢂ104
(5.5ꢀ0.5)ꢂ106
(6.4ꢀ0.4)ꢂ106
(2.7ꢀ0.1)ꢂ106
(4.2ꢀ0.3)ꢂ106
(2.6ꢀ0.9)ꢂ106
(1.9ꢀ0.2)ꢂ106
(5.2ꢀ0.4)ꢂ106
6.00ꢂ10ꢁ2
1.50ꢂ10ꢁ2
3.50ꢂ10ꢁ3
1.75ꢂ10ꢁ3
1.14ꢂ10ꢁ3
(8.0ꢀ0.3)ꢂ10ꢁ5
(6.8ꢀ0.8)ꢂ10ꢁ5
(1.4ꢀ0.5)ꢂ10ꢁ4
(2.8ꢀ0.1)ꢂ10ꢁ4
(2.9ꢀ0.6)ꢂ10ꢁ4
88ꢀ5
230ꢀ27
349ꢀ99
561ꢀ81
861ꢀ77
1346
www.chemphyschem.org
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemPhysChem 2011, 12, 1342 – 1350

Surfactant Host–Guest Complexes in Equilibrium with Micellar Aggregates
2.3.5. Quantitative Explanation
In an effort to develop a kinetic
model we considered the ab-
sence of interactions between
micelles and CB7 as well as the
existence of three simultaneous
reaction paths (Scheme 3): the
reaction of the free substrate in
the aqueous medium, the reac-
tion of the complexed substrate
with CB7 and the reaction of the
substrate associated with the mi-
celle.
This mechanistic scheme al-
lowed us to derive the following
equation for the rate constant
[Eq. (3)]:
kw þ kCB7KCB7½CB7ꢂf þ kmKm½Dnꢂ
kobs
¼
1 þ KCB7½CB7ꢂf þ Km½Dnꢂ
ð3Þ
Figure 7. Titration of 275 mL of C18TACl micelles (9 mm) with CB7 (0.7 mm) into 1.459 mL of CB7 (0.7 mm) in
92 steps at 258C. a) Calorimetric traces (heat flow against time). b) Enthalpy process versus [C18TACl] in the cell.
c) First derivative of curve b calculated numerically from interpolated values.
To solve Equation (3) it is nec-
essary to know the values of
cmcapp, which were kinetically
incorporated into the micelle and/or the host–guest complex
micellizes. To address this question, the experimental behav-
iour in the solvolysis of MBSC should be analyzed at surfactant
concentrations beyond the micellization point, in the presence
of cationic micelles and also in the CB7–surfactant mixed
system.
As an example, the influence of the surfactant concentration
in the absence and in the presence of CB7 is shown in Fig-
ure 8a,b for the case of C12TABr. If we only focus on the behav-
iour after the cmc when plotting kobs versus [Dn], it can be
seen that the results in the absence and in the presence of
CB7 are completely identical. This clearly shows the absence of
any kind of interaction between CB7 and the micelle. If an in-
teraction were established, this would change the polarity of
the medium and consequently an effect should be observed in
the solvolysis of MBSC due to its high sensitivity to the polarity
of the medium.
Scheme 3.
evaluated as the minimal surfactant concentration where an
appreciable change in kobs is observed (see Figure 4) as well as
the concentration of uncomplexed CB7, [CB7]f, for each surfac-
tant concentration.
1
In an effort to confirm this behaviour we performed H NMR
for the case of C16TA+, paying special attention to the chemical
shifts of the N(CH3)3 group of the surfactant.
From Figure S-7 (see the Supporting Information) we can
see that at high concentration of surfactant the experiments in
absence and in presence of CB7 converge to the same point.
This fact corroborates our interpretation, that is, absence of in-
teraction between CB7 and the micelle. If CB7 were located at
the stern layer of the cationic micelles, this would change the
observed chemical shifts of the ammonium group.
The concentration of uncomplexed CB7 can be obtained by
means of a simulation procedure, supposing that the complex
formed between the surfactant molecules and CB7 has a stoi-
chiometric ratio of 1:1, as found for the CB7–MBSC complex.
The complexation constants for binding of the substrate by
CB7 and for surfactant monomers by CB7 are expressed as
[Eq. (4)]:
½CB7 ꢁ MBSCꢂ
½MBSCꢂw½CB7ꢂf
½CB7 ꢁ Surfꢂ
ð4Þ
KCB7
¼
Ks ¼
½Surfꢂmon½CB7ꢂf
ChemPhysChem 2011, 12, 1342 – 1350
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemphyschem.org
1347

L. Garcꢀa-Rꢀo et al.
complexed CB7 [Eq. (8)]:
3
2
ð8Þ
ð9Þ
a½CB7ꢂf þb½CB7ꢂf þg½CB7ꢂfþ½CB7ꢂT¼ 0
where [Eqs. (9)–(11)]:
a ¼ KsKCB7
b ¼ KsKCB7ð½MBSCꢂTþ½SurfꢂTþ½CB7ꢂTÞ þ Ks þ KCB7
g ¼ KCB7ð½MBSCꢂTꢁ½CB7ꢂTÞ þ Ksð½SurfꢂTꢁ½CB7ꢂTÞ þ 1
ð10Þ
ð11Þ
In order to obtain [CB7]f we need to solve Equations (8)–(11)
by using the values Ks and KCB7 obtained previously. Solving
these equations allowed us to obtain the concentration of un-
complexed CB7 for each surfactant concentration prior to the
cmcapp. Above the cmcapp the concentration of uncomplexed
CB7 is assumed to be constant and equal to the value ob-
tained at cmcapp. The [CB7]f and [Dn] values were used to fit
the experimental kobs values to Equation (3). As an example,
Figure 4 shows the fit of kobs versus [Surfactant] in the pres-
ence of a total concentration of CB7 of [CB7]=7ꢂ10ꢁ4 m on
using the concentration of uncomplexed CB7 calculated with
Equations (8)–(11). The fitted parameters corresponding to
Equation (3) are shown in Table 2.
The values obtained for the parameters in simple micellar
systems and mixed CB7-micelle systems for the reaction in the
micellar pseudophase, km and Km, are shown in Tables 1,2. The
values of these parameters provide valuable information about
the micellar aggregate structure. Km is related to the hydropho-
bic character of the inner cavity of the micelle, whereas km
gives information about the polarity of the medium. Thus, if
there is some kind of interaction between CB7 and cationic mi-
celles, this will be reflected in the values of Km and km. As can
be seen, there is good agreement between the values of km
and Km obtained in the presence and absence of CB7, a finding
that clearly indicates the validity of the applied model.
2.3.6. Variation of Uncomplexed CB7 Concentration with the
Chain Length of the Surfactant
For each surfactant, it is possible to obtain the concentration
of uncomplexed CB7 from a calibration curve (Figure 1). On re-
writing Equation (1) and using the values of KCB7, kCB7 and kw
previously obtained, we can determine the concentration of
uncomplexed CB7 [Eq. (12)]:
Figure 8. Influence of C12TABr concentration on the observed rate constant
~
for the solvolysis of MBSC: a) in the absence of CB7 ( ), b) in the presence
of [CB7]=7ꢂ10ꢁ4 m ( ) and c) kobs versus [Dn] in absence ( ) and in pres-
~
*
*
ence ( ) of CB7.
kw ꢁ kobs
The mass balances for the total concentrations of CB7, sur-
factant and MBSC for surfactant concentrations below the
cmcapp are given by Equations (5)–(7):
½CB7ꢂf ¼
ð12Þ
KCB7ðkobs ꢁ kCB7
Þ
The values of %CB7f in equilibrium with the micellar system
and the maximum values of kobs in the plot of kobs versus the
surfactant concentration are shown in Table 3. The maximum
values of kobs are lower than the value obtained in bulk water
[kw =(6.44ꢀ0.01)ꢂ10ꢁ3 sꢁ1] and this is due to the presence of
uncomplexed CB7 at the micellization point.
½CB7ꢂT ¼ ½CB7ꢂf þ ½CB7 ꢁ MBSCꢂ þ ½CB7 ꢁ Surfꢂ
½SurfꢂT ¼ ½Surfꢂmon þ ½CB7 ꢁ Surfꢂ
ð5Þ
ð6Þ
ð7Þ
½MBSCꢂT ¼ ½MBSCꢂw þ ½CB7 ꢁ MBSCꢂ
The combination of these equations with the binding con-
stants gives a third order equation for the concentration of un-
The percentage of uncomplexed CB7 increases with the
length of the hydrocarbon chain of the surfactant (see
1348
www.chemphyschem.org
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemPhysChem 2011, 12, 1342 – 1350

Surfactant Host–Guest Complexes in Equilibrium with Micellar Aggregates
of the binding constants with CB7 are significantly higher than
Table 3. Values of [CB7]f in equilibrium with the micellar system in the
presence of different surfactants.
those for b-CD, and this is reflected in the percentage of free
CB7.
Surfactant
kobs max. [sꢁ1
]
%CB7f
C6TABr
C8TABr
C10TABr
C12TABr
C14TABr
C16TACl
C18TACl
(6.43ꢀ0.01)ꢂ10ꢁ3
(6.42ꢀ0.02)ꢂ10ꢁ3
(6.39ꢀ0.01)ꢂ10ꢁ3
(6.09ꢀ0.02)ꢂ10ꢁ3
(5.96ꢀ0.03)ꢂ10ꢁ3
(5.706ꢀ0.003)ꢂ10ꢁ3
(5.203ꢀ0.008)ꢂ10ꢁ3
0.01
0.01
0.08
0.46
0.66
1.05
1.95
3. Conclusions
The results obtained in this study allow us to conclude that for
low surfactant concentrations a CB7–surfactant complex is
formed in a competitive model by break down of the CB7–
MBSC complex. The competitive formation of the CB7–surfac-
tant complex occurs until the concentration of monomers
reaches the value at which the micellization process begins.
The values of the binding constants between CB7 and surfac-
tants are essentially independent of the increasing length of
the hydrocarbon chain of the surfactant and these values are
significantly higher than those obtained with b-CD. A small
percentage of uncomplexed CB7 exists in equilibrium with the
cationic micelles and this percentage increases with the hydro-
phobic character of the surfactants.
Figure 9). An increase in the hydrophobicity of the surfactant
gives rise to an increase in the percentage of uncomplexed
CB7. The increased hydrophobicity due to the nature of the
surfactant has no effect on its affinity to complex with CB7,
but it does increase its tendency to micellize.
Acknowledgements
This work was supported by the Ministerio de Ciencia y Tecnolo-
gꢀa (Project CTQ2008-04420/BQU) and Xunta de Galicia
(PGIDIT07-PXIB209041PR, PGIDIT10-PXIB209113PR and 2007/085).
M. PessÞgo, N. Basilio and J. A. Moreira acknowledge FCT for
Ph.D. Grant SFRH/BD/60911/2009, SFRH/BD/29218/2006 and sab-
batical grant SFRH/BSAB/737/2007, respectively.
Keywords: cyclodextrins · host–guest systems · kinetics ·
supramolecular chemistry · surfactants
[1] D. J. Cram, J. M. Cram, Science 1974, 183, 803–809.
[2] H. J. Schneider, Angew. Chem. 1991, 103, 1419–1439; Angew. Chem. Int.
Ed. Engl. 1991, 30, 1417–1436.
[3] M. L. Bender, M. Komiyama, Cyclodextrin Chemistry, Springer, Berlin,
1978.
[4] J. Szejtli, T. Osa, Cyclodextrins, Vol. 3, Elsevier, Oxford, 1996.
[5] W. L. Mock in Comprehensive Supramolecular Chemistry, Vol. 2 (Ed.: F.
Vçgtle), Elsevier, New York, 1996, pp. 477–493.
[6] J. Lagona, P. Mukhopadhyay, S. Chakrabarti, L. Isaacs, Angew. Chem.
2005, 117, 4922–4949; Angew. Chem. Int. Ed. 2005, 44, 4844–4870.
[7] J. Kim, I.-S. Jung, S.-Y. Kim, E. Lee, J.-K. Kang, S. Sakamoto, K. Yamaguchi,
J. Am. Chem. Soc. 2000, 122, 540–541.
[8] W. L. Mock, Top. Curr. Chem. 1995, 175, 1–24.
[9] R. Hoffmann, W. Knoche, C. Fenn, H.-J. Buschmann, J. Chem. Soc. Fara-
day Trans. 1994, 90, 1507–1511.
[10] J. W. Lee, S. Samal, N. Selvapalan, H.-J. Kim, K. Kim, Acc. Chem. Res.
2003, 36, 621–630.
[11] K. Kim, Chem. Soc. Rev. 2002, 31, 96–107.
Figure 9. Variation of the percentage of uncomplexed a) CB7 and b) b-CD in
equilibrium with the micellar system.
[12] A. I. Day, A. P. Arnold, R. J. Blanch, B. Snushall, J. Org. Chem. 2001, 66,
8094–8100.
[13] A. I. Day, R. J. Blanch, A. P. Arnold, S. Lorenzo, G. R. Lewis, I. Dance,
Angew. Chem. 2002, 114, 285–287; Angew. Chem. Int. Ed. 2002, 41, 275–
277.
[14] H.-J. Kim, W. S. Jeon, Y. H. Ko, K. Kim, Proc. Natl. Acad. Sci. USA 2002, 99,
5007–5011.
[15] D. Sobransingh, A. E. Kaifer, Org. Lett. 2006, 8, 3247–3250.
[16] C. Marquez, R. R. Hudgins, W. M. Nau, J. Am. Chem. Soc. 2004, 126,
5806–5816.
[17] R. Wang, L. Yuan, H. Ihmels, D. H. Macartney, Chem. Eur. J. 2007, 13,
6468–6473.
As can be seen in Figure 9, there is a higher percentage of
uncomplexed b-CD[49] than CB7 in equilibrium with the micellar
system for trimethylalkylammonium surfactants. The percent-
age of uncomplexed b-CD in the case of C18TACl is approxi-
mately 21 times higher than that of CB7. This difference can be
explained on the basis of the binding constants between the
surfactant and these hosts. As already mentioned, the values
ChemPhysChem 2011, 12, 1342 – 1350
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemphyschem.org
1349

L. Garcꢀa-Rꢀo et al.
[18] L. Yuan, R. B. Wang, D. H. Macartney, J. Org. Chem. 2007, 72, 4539–
4542.
[34] A. A. Rafati, A. Bagheri, H. Iloukhani, M. Zarinehzad, J. Mol. Liq. 2004,
116, 37–41.
[35] E. Junquera, J. Gonzalez Benito, L. Pena, E. Aicart, J. Colloid Interface Sci.
1994, 163, 355–361.
[36] G. Gonzalez-Gaitano, A. Crespo, A. Compostizo, G. Tardajos, J. Phys.
Chem. B 1997, 101, 4413–4421.
[19] R. Wang, L. Yuan, D. H. Macartney, Chem. Commun. 2006, 2908–2910.
[20] W. L. Mock, N.-Y. Shih, J. Org. Chem. 1986, 51, 4440–4446.
[21] S. Liu, C. Ruspic, P. Mukhopadhyay, S. Chakrabarti, P. Y. Zavalij, L. Isaacs,
J. Am. Chem. Soc. 2005, 127, 15959–15967.
[37] G. Patonay, M. E. Rollie, I. M. Warner, Anal. Chem. 1985, 57, 569–571.
[38] A. A. Rafati, A. Bagheri, Bull. Chem. Soc. Jpn. 2004, 77, 485–490.
[39] D. Jezequel, A. Mayaffre, P. Letellier, Can. J. Chem. 1991, 69, 1865–1871.
[40] M. S. Bakshi, J. Colloid Interface Sci. 2000, 227, 78–83.
[41] L. Garcia-Rio, P. Herves, E. Iglesias, J. R. Leis, J. C. Mejuto, J. Perez-Juste,
Recent Res. Dev. Phys. Chem. 2000, 4, 101–133.
[42] E. Iglesias, A. Fernandez, J. Chem. Soc. Perkin Trans. 2 1998, 1691–1700.
[43] L. Garcia-Rio, M. Mꢃndez, M. R. Paleo, F. J. Sardina, J. Phys. Chem. B
2007, 111, 12756–12764.
[44] R. M. Forbes, H. Maskill, J. Chem. Soc. Chem. Commun. 1991, 854–856.
[45] I. S. Koo, T. W. Bentley, G. Llewellyn, K. Yang, J. Chem. Soc. Perkin Trans. 2
1991, 1175–1179.
[46] I. S. Koo, T. W. Bentley, D. H. Kang, I. Lee, J. Chem. Soc. Perkin Trans. 2
1991, 175–179.
[22] K. Kim, H.-J. Kim in Encyclopedia of Supramolecular Chemistry (Eds.: J. L.
Atwood, J. W. Steed), Marcel Dekker, New York, 2004, pp. 390–397.
[23] K. Kim, N. Selvapalam, Y. H. Ko, K. M. Park, D. Kim, J. Kim, Chem. Soc. Rev.
2007, 36, 267–279.
[24] H.-J. Kim, J. Heo, W. S. Jeon, E. Lee, J. Kim, S. Sakamoto, K. Yamaguchi,
K. Kim, Angew. Chem. 2001, 113, 1574–1577; Angew. Chem. Int. Ed.
2001, 40, 1526–1529.
[25] Y. H. Ko, E. Kim, I. Hwang, K. Kim, Chem. Commun. 2007, 1305–1315.
[26] Y. H. Ko, H. Kim, Y. Kim, K. Kim, Angew. Chem. 2008, 120, 4174–4177;
Angew. Chem. Int. Ed. 2008, 47, 4106–4109.
[27] I. W. Wyman, D. H. Macartney, J. Org. Chem. 2009, 74, 8031–8038.
[28] H.-J. Buschmann, K. Jansen, E. Schollmeyer, J. Inclusion Phenom. Macro-
cyclic Chem. 2000, 37, 231–236.
[29] D. J. Jobe, V. C. Reinsborough, S. C. Wetmore, Langmuir 1995, 11, 2476–
2479.
[30] T. Utsuki, H. Brem, J. Pitha, T. Loftsson, T. Kristmundsdottir, B. M. Tyler, A.
Olivi, J. Controlled Release 1996, 40, 251–260.
[31] G. M. Nicolle, A. E. Merbach, Chem. Commun. 2004, 854–855.
[32] A. J. M. Valente, M. Nilsson, O. Sçdreman, J. Colloid Interface Sci. 2005,
281, 218–224.
[47] N. Basilio, L. Garcꢀa-Rꢀo, J. A. Moreira, M. PessÞgo, J. Org. Chem. 2010,
75, 848–855.
[48] B. Honig, A. Nicholls, Science 1995, 268, 1144–1149.
[49] B. Dorrego, L. Garcꢀa-Rꢀo, P. Hervꢃs, J. R. Leis, J. C. Mejuto, J. Pꢃrez-Juste,
J. Phys. Chem. B 2001, 105, 4912–4920.
[33] R. Palepu, J. E. Richardson, V. C. Reinsborough, Langmuir 1989, 5, 218–
221.
Received: December 15, 2010
Published online on April 6, 2011
1350
www.chemphyschem.org
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemPhysChem 2011, 12, 1342 – 1350