Evidence of higher complexes between cucurbit[7]uril and cationic surfactants.

Abstract

The host-guest assembly of CB7 with a series of alkyl(trimethyl)ammonium (C(n)TA(+)) surfactants of different chain lengths (n=6-18) has been studied. The complexation behaviour was investigated by NMR spectroscopy, isothermal titration calorimetry and kinetics measurements. The combined results of these techniques provided evidence for the formation of 1:1 inclusion and 2:1 external complexes in the cases of C(n)TA(+) with n=12-18. The binding constants for the 1:1 complexes are independent of the alkyl chain length of the surfactant, whereas a relationship between K(2:1) and the chain length of the surfactant was found for the 2:1 complexes.

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DOI: 10.1002/chem.201103049
Evidence of Higher Complexes Between Cucurbit[7]uril and
Cationic Surfactants
M. PessÞgo,[a]J. A. Moreira,[b]and L. Garcia-Rio*[a]
Introduction
The cucurbit[n]urils (CBn, n=5–10) are a family of cyclic
host molecules comprising n glycoluril units linked by a pair
of methylene groups.[1–4]The two identical carbonyl-fringed
portals have a considerable negative charge density, which
facilitates the binding of metal ions and cationic organic
compounds, whereas the inner cavities are relatively hydro-
phobic and can host neutral molecules that fit within.[5–12]
Amphiphilic molecules that contain a long alkyl chain,
such as surfactants, have the possibility of covering a wide
range of hydrophobicity. We recently reported that CB7 and
cationic surfactants produce very stable 1:1 inclusion com-
plexes; their binding constants are essentially independent
of the alkyl chain and the complexation of the substrates is
mainly controlled by electrostatic effects.[13]The CBn family
has shown a high propensity for forming a variety of strong
and stable supramolecular complexes with a higher stoichi-
ometry than 1:1. Wyman and Macartney demonstrated that
CB7 can form very stable host–guest complexes (1:1 and
2:1) with dicationic (Scheme 1)[14,15]and tetracationic[16]
guests. The 1:1 complexes are formed with 1 equivalent of
CB7 positioned over the central chain. The addition of a
second equivalent of the host encapsulates one of the end
groups and results in the translocation of the first CB7 to
the other end group.
Recently, studies of the complexation between CB7 and
the cationic guests Sanguinarine[17]and Thioflavin T[18]were
reported and the formation of 1:1 and 2:1 complexes was
found. In these cases the addition of an excess of CB7 pro-
duced an inclusion complex with two host molecules in
which the positive charge of the guest interacts with the car-
bonyl oxygen atoms of the two hosts.
Tuncel and Steinke[19]studied the polymerisation of poly-
(iminohexamethylene) in the presence of CB6 (Scheme 2).
It was suggested that the CB6 could bind ammonium ions to
form inclusion and external complexes and that the external
complex may interfere in the formation of dynamic physical
cross-links.
In the study reported herein we investigated the assembly
of host–guest complexes of CB7 with a series of trimeth-
ylammonium surfactants (CnTA+ +, n=6–18). The complexes
Abstract: The host–guest assembly of
CB7withaseriesofalkyl(trime-
thyl)ammonium (CnTA+ +) surfactants
of different chain lengths (n=6–18)
has been studied. The complexation
behaviour was investigated by NMR
spectroscopy, isothermal titration calo-
rimetryandkinetics
The combined results of these techni-
measurements.
ques provided evidence for the forma-
tion of 1:1 inclusion and 2:1 external
complexes in the cases of CnTA+ +with
n=12–18. The binding constants for
the 1:1 complexes are independent of
the alkyl chain length of the surfactant,
whereas a relationship between K2:1
and the chain length of the surfactant
was found for the 2:1 complexes.
Keywords: inclusion compounds ·
kinetics · NMR spectroscopy · su-
pramolecular chemistry · surfac-
tants
[a] M. PessÞgo, Prof. L. Garcia-Rio
Departamento Qu?mica F?sica
Centro Singular de Investigaci?n en Qu?mica Biol?gica
y Materiales Moleculares (CIQUS)
Universidad de Santiago, 15782 Santiago (Spain)
E-mail: luis.garcia@usc.es
[b] Dr. J. A. Moreira
CIQA, Departamento de Qu?mica e
Farm?cia, 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/chem.201103049.
Scheme 1.
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were characterised in solution by NMR spectroscopy, iso-
thermal titration calorimetry (ITC) and kinetics measure-
ments. The results show the formation of complexes with 1:1
and 2:1 stoichiometries for surfactants with chain length n?
12. The combination of experimental techniques allowed us
to confirm that the complexes with 1:1 stoichiometry are
due to the formation of an inclusion complex between the
surfactant and CB7, whereas the second CB7 present in the
2:1 complexes forms an external complex in which both
CB7 molecules are involved in the stabilisation of the posi-
tive charge.
Experimental Section
All surfactants (CnTA+ +) were supplied by Aldrich in the highest availa-
ble purity and were used without further purification. Cucurbit[7]uril was
synthesised by using the procedure described by Nau and co-workers[20]
and the different CBn were separated by fractional crystallisation from
concentrated hydrochloric acid.
ITC experiments: Isothermal titration calorimetry (ITC) experiments
were performed on a VP-ITC instrument from MicroCal at 258 8C with
stirring at 459 rpm. The ITC experiments were performed in two differ-
ent ways: in one case, solutions of CB7 were placed in the reaction cell
and each CnTA+ +solution was added by microsyringe to the CB7 solu-
tions, and in the other experiments, the addition of reactants was re-
versed.
Competitive experiments: The absorption spectra were recorded by UV/
Vis spectroscopy in a Cary UV/Vis spectrophotometer thermostatted at
25.0?0.18 8C. A solution of trans-4-[4-(dimethylamino)styryl]-1-methylpyr-
idinium iodide (DSMI+ +), which was used as the competing guest, was
prepared in water. In all cases the DSMI+ +concentration was 1.17?
10?5m.
NMR experiments: The stock solutions were prepared in D2O (99.9%).
The surfactant–CB7 systems for NMR measurements were prepared by
mixing the appropriate volumes of stock solutions of CB7 and surfactant.
In all cases the CnTA+ +concentration (1.3 mm) was kept constant, below
the critical micellar concentration (cmc), and the CB7 concentration was
varied.
1H NMR and diffusion-ordered NMR spectroscopy (DOSY) were carried
out at 258 8C on a Varian Inova 400 spectrometer. The DOSY spectra
were acquired with the standard stimulated echo pulse sequence using
LED and bipolar gradient pulses.[21]Square-shaped pulsed gradients (G)
of 2 ms duration were applied with the power increased linearly from 2.1
to 69.7 cm?1in 20 steps. To obtain reliable results for the diffusion coeffi-
cient, the diffusion time (D) of the experiment was optimised for each
sample to a value between 50 and 80 ms. The raw data were processed by
using the MestreC program.
Saturation transfer difference (STD) and rotating frame Overhauser
effect spectroscopy (ROESY) experiments were performed on a Varian
Inova 750 spectrometer. The signals of CB7 were saturated in independ-
ent STD experiments with Gaussian-shaped pulses of 50 ms duration. For
each saturated signal, the STD experiments were repeated with satura-
tion times of 0.5, 1, 2 and 3 s.
Kinetic measurements: The reaction kinetics were monitored by UV/Vis
spectroscopy at 270 nm in a Cary UV/Vis spectrophotometer thermostat-
ted at 25.0?0.18 8C. A solution of 4-methoxybenzenesulfonyl chloride
(MBSC), which was used as a chemical probe, was prepared in acetoni-
trile. In all cases the MBSC concentration was 1.0?10?4m. Surfactant–
CB7 systems were prepared by mixing appropriate volumes of aqueous
stock solutions of CB7 and surfactant. The absorbance–time data for all
kinetic experiments were fitted to a first-order integrated rate equation.
Results and Discussion
Isothermal titration calorimetry: The ITC experiments were
performed in two different ways. In one case the CB7 solu-
tions were placed in the reaction cell and each CnTA+ +solu-
tion was added to the CB7 solutions and in the other type
of experiment the addition of reactants was reversed.
The results obtained in the titrations of surfactants with
alkyl chains of less than 12 carbon atoms are independent of
the manner in which the ITC was performed. The use of sur-
factants with alkyl chains longer than 12 carbons gave rise
to different behaviour. In these cases the effect of the order
of addition, for C16TACl as an example, is shown in
Figure 1. The binding isotherm data were fitted to the theo-
retical curves “One Set of Sites” and “Two Sets of Sites”,
supplied by Microcal in Figure 1a and b, respectively.
As can be seen in Figure 1, the results obtained from the
calorimetric measurements show a dependence on the loca-
tion of the reactants. In the cases in which CB7 is in the sy-
ringe (Figure 1a), the binding isotherms remain practically
unchanged on increasing the surfactant concentration until
near the equivalence point. However, in the case in which
CB7 is placed in the cell (Figure 1b), a gradual decrease in
the binding isotherms is observed up to near the equivalence
point, which suggests that in this region a 2:1 complex is
formed between CB7 and C16TACl. The binding constants
obtained for the 1:1 and 2:1 complexes formed between
CB7 and CnTA+ +are shown in Table 1 and Figure 2.
The value of the binding constant K1:1for C10TABr was
also confirmed by competitive experiments by using trans-4-
[4-(dimethylamino)styryl]-1-methylpyridinium
(DSMI+ +) as the competitor guest (see the Supporting Infor-
mation). The value obtained by the competitive method,
iodide
Scheme 2.
Table 1. Binding constants for 1:1 and 2:1 complexes for CnTA+ +, ob-
tained by ITC experiments.
SurfactantK1:1[10?6m?1]K2:1[10?3m?1]
C6TABr
C8TABr
C10TABr
C12TABr
C14TABr
C16TACl
C18TABr
5.5?0.5
6.4?0.6
2.6?0.1
2.0?0.3
4.3?0.2
5.5?0.2
8.5?0.5
–
–
–
1.0?0.3
4.3?0.5
15.4?3
28.3?5
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K1:1=(4.0?0.5)?106m?1, is compatible with the value ob-
tained by ITC, K1:1=(2.6?0.1)?106m?1.
It can be seen from Figure 2 that the values obtained for
the 1:1 complexes are independent of the length of the alkyl
chain of the surfactant, whereas the values for the 2:1 com-
plexes show a relationship exists between K2:1and the chain
length of the surfactants.
Cabaleiro-Lago[22]et al. studied the host–guest interaction
between b-cyclodextrin (b-CD) and CnTA+ +and they found
evidence for the formation of a 2:1 inclusion complex in the
case of C16TA+ +. In the case of b-CD, a relationship exists
between the binding constants and the chain length of the
surfactants. As mentioned above, the magnitude of K2:1is
also related to the length of the alkyl chain of the surfac-
tants, which suggests the formation of 2:1 inclusion com-
plexes between CB7 and CnTA+ +with n?12 (Scheme 3).
However, additional experiments would be required to es-
tablish the possible structure of the 2:1 complex.
Diffusion
CnTA+ +with CB7 was investigated in detail by performing
1H NMR and DOSY experiments in which the concentration
of CnTA+ +was kept constant (below the cmc) and the CB7
concentration was varied. The two components, CB7 and
CnTA+ +, gave rise to peaks that do not overlap, which makes
it possible to distinguish individual signals from CB7 and
the surfactant. This situation facilitates the evaluation of the
NMR Measurements: Thecomplexation of
Figure 1. a) Titration of CB7 (1.76 mm) with 1.459 mL of C16TACl
(0.13 mm) at 258 8C. Top: Calorimetric traces (heat flow against time) with
the “OneSites” model: Chi2/DoF=9791; N=(0.857?0.00126) sites; K=
((2.65?106)?(1.22?105)) m?1; DH=(?1.023?104?27.12) calmol?1; DS=
?4.92 calmol?1deg?1. Bottom: Binding isotherms (obtained by integrat-
ing the peaks of the upper curve) versus molar ratio. b) Titration of
C16TACl (0.9 mm) with 1.459 mL of CB7 (0.06 mm) at 258 8C with the
“TwoSites” model: Chi2/DoF=1.455?104; N1=(0.900?0) sites; K1=
((1.52?104)?(2.66?103)) m?1;
13.9 calmol?1deg?1; N2=(0.906?0.00309) sites; K2=(5.45?106?0) m?1;
DH2=(?9494?42.2) calmol?1; DS2=?1.02 calmol?1deg?1. Top: Calori-
metric traces (heat flow against time). Bottom: Binding isotherms (ob-
tained by integrating the peaks of the upper curve) versus molar ratio.
DH1=(?1559?293) calmol?1;
DS1=
Figure 2. Binding constants for 1:1 (*) and 2:1 (*) complexes, obtained
by calorimetric measurements for each surfactant.
Scheme 3.
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data from the self-diffusion experiments. Quantitative analy-
sis of the intensity of a relevant echo peak in the diffusion
spectrum provides the corresponding translational diffusion
coefficient of the corresponding molecule. This was achieved
by non-linear fitting of the signal intensity to the Stejskal–
Tanner Equation (1)[23]in which I is the measured signal in-
tensity, I0is the signal intensity at the lowest gradient pulse
power, g is the magnetogyric ratio of the observed nucleus
and the rest of the parameters are defined above. In all the
experiments, the decay of the signal intensity gave good fits
to Equation (1), which shows that they represent a single
self-diffusion coefficient. A typical plot of intensity decay
versus g2G2d2(D?d/3) and the non-linear fit to Equation (1)
is shown in Figure 3.
I ¼ I0exp½?Dg2d2ðD ? d=3Þ?
ð1Þ
All the peaks corresponding to CB7 were analysed and
similar results were obtained. In the case of CnTA+ +, the
peak arising from the methyl protons of the head group was
used as a reference. The association between CnTA+ +and
CB7 was studied by varying the concentration of CB7 for a
constant concentration of surfactant below the cmc.
The self-diffusion coefficients (Dobs) for C8TA+ +and CB7
as a function of the concentration of CB7 are shown in
Figure 4. The experimental data can be split into two differ-
ent regions. First, as the concentration of CB7 increases the
self-diffusion coefficients of the surfactant decrease due to
the formation of an inclusion complex with CB7 until the
maximum concentration of the complex is reached (Fig-
ure 4,I). After this point (Figure 4,II), the self-diffusion of
the surfactant remains constant because no more complexes
are formed. On the other hand, in the case of CB7, the self-
diffusion coefficients are almost constant from the beginning
with only a slight increase observed, which could be attribut-
ed to the increase in free CB7. From the experimental data
one can observe a small difference between the self-diffu-
sion coefficients of CB7 and the complex. This suggests that
CB7 and the complex are of a similar size, which indicates
that the majority of the surfactant molecule is inside the
CB7 cavity and only a small portion, such as the head
group, sticks out.
To study the experimental data in more detail, and from a
quantitative point of view, a model for the formation of a
1:1 complex allows us to derive Equation (2) for the ob-
served self-diffusion (see the Supporting Information).
DS;obs¼DS;fþ K1:1DCB7?S½CB7?
1 þ K1:1½CB7?
ð2Þ
A non-linear least-squares fit was performed to determine
the unknown values for different variables. All variables
were fitted simultaneously to both sets of experimental data
for self-diffusion coefficients of CB7 and the surfactant.
To fit the experimental data it is necessary to know the
values of the binding constants between CB7 and the surfac-
tant. These values were determined by calorimetric meas-
urements. Global fits were performed on the assumption
that only 1:1 complexes are formed between CB7 and the
surfactant. The model for self-diffusion coefficients for the
1:1 complex can be used to obtain the values for the un-
known variables DS,f, DCB7,fand DCB7-S. One of the limita-
tions of this technique is the relative magnitude of the self-
diffusion coefficients of the species present in the systems;
whereas the coefficients of the surfactant and CB7 differ sig-
nificantly, the self-diffusion coefficients for CB7 and the
complex are similar. The fitting of CnTA+ +(n=6, 8 and 10)
was performed with the values of Ds,fand K1:1locked. The
results obtained are summarised in Table 2.
Similar behaviour was found for CnTA+ +with n=6–10,
whereas in the case of n=12 and 14, a different pattern was
observed. In these cases (Figure 5), after the initial decrease
in the self-diffusion coefficients at the beginning of the
curve, the diffusion does not reach a constant value. A
slight, but perceptible decrease is observed and this slope in-
dicates the formation of a 2:1 complex.
Figure 3. Representative echo decays of C8TABr in the absence (*) and
in the presence of 1 mm CB7 (*). The data are fitted to an exponential
function (solid lines).
Figure 4. Self-diffusion coefficients of C8TABr (*) and CB7(*) with in-
creasing concentrations of CB7 and at [C8TABr]=1.3?10?3m. The solid
line shows the fit to the self-diffusion coefficient model for the 1:1 com-
plex.
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The experimental data were fitted to the model on the as-
sumption of 1:1 complexation. As can be seen from
Figure 5, it is evident that the model (solid line) fails to re-
produce the experimental behaviour.
The model predicts a levelling off of the self-diffusion co-
efficients of the surfactant at high CB7 concentrations and
this deviation is not due to scatter in the data. The decrease
is monotonic and perceptible. The formation of a second
complex with a self-diffusion coefficient less than that of the
1:1 complex explains the experimental behaviour. A model
that takes into account the formation of two complexes, 1:1
and 2:1, was used to reproduce the experimental data
[Eq. (3), see the Supporting Information].
DS;obs¼DS;fþK1:1DCB7?S½CB7? þ K1:1K2:1DðCB7Þ2?S½CB7?2
1 þ K1:1½CB7? þ K1:1K2:1½CB7?2
ð3Þ
The results obtained for the case of C12TA+ +were fitted
by using both the models described in the Supporting Infor-
mation. A comparison of the results for the 1:1 and 2:1 fit-
ting procedure clearly shows that the model including a 2:1
complex yields better agreement with the experimental
data. For the initial decrease, both models reproduce the ex-
perimental data, but the second slope at higher CB7 concen-
trations can only be reproduced if the formation of a 2:1
complex is considered. The experimental data were fitted to
these models by using the values of the binding constants
for the 1:1 and 2:1 complexes obtained previously. The
model self-diffusion coefficients for the 1:1 and 2:1 com-
plexes were used to obtain the values of the unknown varia-
bles DS,f, DCB7,f, DCB7-Sand D(CB7)2?S. The results obtained are
summarised in Table 3.
In the cases of C16TACl and C18TABr, diffusion studies
were not possible due to the formation of molecular aggre-
gates between these surfactants and CB7. The high molecu-
lar weight of these aggregates changed the relaxation times
and the protons in the complex and free species were signifi-
cantly different. This change causes peak-broadening in the
1H NMR spectra, which resulted in spectra with a great deal
of noise thus preventing accurate analysis.
1H NMR measurements: Systematic NMR studies provided
valuable information on the stoichiometries and structures
of the complexes. In the1H NMR spectra of the CB7 host–
guest complexes, the complexation-induced changes in the
chemical shifts (Dd=dbound?dfree) of the proton resonances
of the guest molecule are very informative as to the average
location of the guest with respect to the CB7 cavity. Upfield
shifts (Dd<0 ppm) are observed for protons located within
the hydrophobic cavity, whereas the deshielding due to the
polar carbonyl groups results in downfield shifts (Dd>
0 ppm) in the resonances of the guest protons in the proxim-
ity of the carbonyl oxygen atoms.[1,3,4,24]
The
C6TABr in the presence of increasing equivalents of CB7
are shown in Figure 6. As can be seen from Figures 6 and S3
1H chemical shifts of the N+ +(Me)3 signals of the
(see the Supporting Information), the
change on gradually increasing the concentration of CB7 up
1H NMR spectra
to equimolar quantities; the chemical shift of the N+ +(CH3)3
group of the surfactant moves upfield. Changes in the spec-
tra are no longer observed at higher CB7 concentrations.
The data in Figure 6 show a good fit (solid line) between
Table 2. Self-diffusion coefficients for a 1:1 complex.
SurfactantDs,f[106cm2s?1]DCB7–S[106cm2s?1]
C6TABr
C8TABr
C10TABr
6.8?0.2
6.35?0.1
5.68?0.04
2.9?0.3
2.6?0.3
2.9?0.1
Figure 5. Self-diffusion coefficients for [C12TABr]=1.3?10?3m with in-
creasing concentration of CB7. The lines show the fits to the model with
a 1:1 complex (solid line) and to the model including a 2:1 complex
(dotted line).
Table 3. Diffusion coefficients for 1:1 and 2:1 complexes for CnTA+ +with
n=12–16.
SurfactantDs,f[106cm2s?1]DCB7–S[106cm2s?1]D(CB7)2–S[106cm2s?1]
C12TABr
C14TABr
C16TACl
C18TABr
5.5?0.1
5.4?0.1
–
–
2.9?0.2
2.7?0.9
–
–
2.2?0.7
2.4?0.9
–
–
Figure 6.1H NMR chemical shifts of the signals of the N+ +(Me)3group of
C6TABr (1.3 mm) as a function of the concentration of CB7 at 258 8C.
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Equation (4) (mathematical[25]model based on a 1:1 host–
guest complex) and the experimental points.
Dd ¼Dd1:1K1:1½CB7?
1 þ K1:1½CB7?
ð4Þ
The effect of complexation on the spectrum of C12TABr
can be seen in Figures 7 and S4 (see the Supporting Infor-
mation). In contrast to the effect observed for surfactants
with shorter alkyl chains (n?10), the
CnTA+ +with n=12 and 14 change at concentrations of CB7
above equimolar quantities.
The experimental data were fitted to Equation (4) and it
is clear that the model based on a 1:1 host–guest complex
does not reproduce the experimental behaviour. To repro-
duce the experimental data, as in the diffusion experiments
(CnTA+ +with n=12 and 14), a mathematical[25]model based
on multiple equilibria (dashed line) was employed [Eq. (5)].
1H NMR spectra of
Dd ¼Dd1:1K1:1½CB7? þ Dd2:1K1:1K2:1½CB7?2
1 þ K1:1½CB7? þ K1:1K2:1½CB7?2
ð5Þ
The observed changes in the
factants after the addition of an excess of CB7 are in good
agreement with the results obtained in the DOSY and ITC
experiments. It is evident that an interaction exists between
the 1:1 complex and a second molecule of CB7 for CnTA+ +
with n?12.
In the free state, CB7 has a symmetry plane and this
makes the protons of the portals equivalent, which in turn
leads to a1H NMR spectrum with two doublets and one sin-
glet. It can be seen from Figure S3 (see the Supporting In-
formation) that the signals corresponding to the protons of
the portals in the CB7 bound state appear as four doublets
and this is consistent with the plane of symmetry in CB7
being broken. This behaviour is also observed in the case of
C8TA+ +.
1H NMR spectra of the sur-
It is known that the length (L) of a fully extended alkyl
chain CnH2n+ +1is approximated by Equation (6).[26]
L ¼ 1:5 þ 1:265ðn?1Þð6Þ
On substituting the height of the pumpkin-shaped CB7
macrocycle,[3]9.1 ?, into this equation, n=7 is obtained as a
rough estimate of the number of carbon atoms in the ali-
phatic chain, in an all-trans conformation, that can be ac-
commodated in CB7. Therefore most of the hydrocarbon
chain of the surfactant can fit inside the CB7 cavity and
only the head group and a small portion of the alkyl chain
of the longest surfactants are exposed to the bulk water.
The hexyl and octyl chains of C6TA+ +and C8TA+ +in an ex-
tended conformation fit adequately into the cavity of CB7
in terms of length. In the complexation of these surfactants
with CB7, the hydrophobic interactions between the host
and guest are maximised by full encapsulation of the alkyl
chains within the host cavity and the strong ion–dipole inter-
actions between the trimethylammonium group and the
portal are maintained, a situation that could result in the
loss of symmetry of the host.
The CB7-induced chemical shifts (Dd) for CnTA+ +with
n=6 and 14 for two different molar ratios are summarised
in Table 4.
The1H NMR spectra of the CB7–CnTA+ +(n=6–14) com-
plexes show significant changes in the chemical shifts of the
aliphatic protons upon complexation. The methylene pro-
tons in the middle part of the alkyl chains located inside the
cavity experience a large upfield shift. The upfield shifts of
the terminal methyl protons gradually decrease on going
from C6TA+ +to C8TA+ +and, finally, a small downfield shift
is observed for CnTA+ +with n?10 (Table 4).
The protons of the head group show a very small up- or
downfield shift, which suggests that the trimethylammonium
groups are close to the portal of CB7.
In the cases of CnTA+ +with n?10, significant changes
were observed in the chemical shifts up to the equivalence
point and then remained constant after the addition of a
large excess of CB7. This behaviour indicates the formation
of only 1:1 complexes between CnTA+ +(n=6–10) and CB7.
Analysis of the chemical shift displacement of the head
group of the surfactant of the initial 1:1 complex formation
Figure 7.1H NMR chemical shifts of the signals of the N+ +(Me)3group of
C12TABr (1.3 mm) as a function of the concentration of CB7 at 258 8C.
Lines show the fits to models for a 1:1 complex (solid line) and multiple
equilibria (dashed line).
Table 4. Induced chemical shifts (Dd, ppm) of the
of the head group (N+ +Me3), methylene (C1) and terminal methyl protons
(Ct) for molar ratios of 1 and 3.
1H NMR resonances
Surfactant
Dd [ppm] Molar ratio of 1
N+ +Me3
C1
Dd [ppm] Molar ratio of 3
N+ +Me3
C1
Ct
Ct
C6TABr
C8TABr
C10TABr
C12TABr
C14TABr
?0.03
0.02
?0.02
?0.09
?0.07
?0.58
?0.43
?0.49
?0.55
?0.56
?0.69
?0.46
0.05
0.04
0.04
?0.03
0.02
?0.02
?0.12
?0.11
?0.58
?0.43
?0.49
?0.58
?0.57
?0.68
?0.43
0.05
0.01
0.03
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shows small upfield shifts of ?0.09 (C12TA+ +) and ?0.07 ppm
(C14TA+ +). After the addition of excess CB7, an increase in
the upfield shifts to ?0.12 (C12TA+ +) and ?0.11 ppm
(C14TA+ +) was observed. However, in the case of the termi-
nal methyl protons (Ct), downfield chemical shifts of
0.04 ppm were initially observed for both surfactants and, as
the concentration of the host increases, these downfield
chemical shifts decrease. This behaviour suggests the exis-
tence of an interaction between the 1:1 complex and a
second molecule of CB7.
As mentioned previously, seven carbon atoms can be ac-
commodated in the cavity of CB7 if the alkyl chain of the
surfactant is in an all-trans conformation. As can be seen
from Figure 8, the terminal methyl protons of C8TA+ +expe-
rience a large upfield shift and a small downfield shift is ob-
served in the case of C10TA+ +. This difference suggests the
possibility that the alkyl chain of C8TA+ +folds back into the
cavity of CB7.
A combination of the results obtained in the ITC and
NMR experiments for CnTA+ +with n?12 has allowed us to
propose the existence of an interaction between the 1:1
complex and a second molecule of CB7. However, the possi-
ble 2:1 complex structure proposed in Scheme 3 is incom-
patible with the chemical shifts observed for Ct. If such a 2:1
inclusion complex is formed between CB7 and CnTA+ +with
n?12, an upfield shift of the terminal methyl protons
should be observed and the magnitude of this upfield shift
should be close to that observed in the cases of CnTA+ +with
n=6 and 8. It is evident that the structure proposed in
Scheme 3 is not consistent with the observed
shifts. There is, however, another possible structure for the
2:1 complex in which both CB7 molecules complex the head
group of the surfactant (Scheme 4).
1H chemical
Structural characterisation of the 2:1 complex by kinetic
measurements: To define as clearly as possible the structure
of the 2:1 complex, we employed kinetic measurements and
NMR techniques, such as1H ROESY and saturation transfer
difference (STD) spectroscopy. To study the mixed CnTA+ +
and CB7 systems, the hydrolysis of methoxybenzenesulfonyl
chloride (MBSC) was used as a chemical probe. The solvoly-
sis of MBSC shows that the reaction is highly susceptible to
changes in the polarity of the medium. These systems were
studied by carrying out experiments in which the surfactant
concentration was kept constant and the CB7 concentration
was varied. It was assumed that the solvolysis of MBSC
takes place in two well-differentiated environments (see the
Supporting Information): water and the CB7 cavity. The ki-
netics of the hydrolysis is presented in Equation (7) in which
kwand kCB7are the rate constants in water and in the CB7
cavity and KCB7is equilibrium constant of CB7.
kobs¼kwþ kCB7KCB7½CB7?f
1 þ KCB7½CB7?f
ð7Þ
As an example, the results obtained for C16TACl in the
presence of CB7 are shown in Figure 9. The experimental
data were fitted to the model in which we assume that the
second molecule of CB7 includes within the cavity the alkyl
chain that is exposed to water in the 1:1 complex (dashed
line). As can be seen from Figure 9, it is evident that this
model does not reproduce the experimental behaviour.
One possible assumption we can make is that in the 2:1
complex both molecules of CB7 complex the head group of
Figure 8.1H NMR chemical shifts of the signals of C1(*) and Ct(&) of
surfactants for 1 (white) and 3 (black) molar ratios.
Scheme 4.
Figure 9. Influence of CB7 concentration on the observed rate constant
for the solvolysis of MBSC in the presence of [C16TACl]=2.1?10?4m.
Lines show the fits to models for a 2:1 complex with both molecules of
CB7 including the alkyl chain of the surfactant (solid line) and with both
molecules of CB7 complexing the head group of the surfactant (dashed
line).
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the surfactant; one of the hosts includes within its cavity the
alkyl chain of the surfactant and the other host would have
an empty cavity with the possibility of forming an inclusion
complex with the chemical probe. A model that takes into
account such a structure for the 2:1 complex was used to re-
produce the experimental results. The results obtained in
the case of C16TACl, fitted by using a model that takes into
account this possible structure (solid line), are shown in
Figure 9. It is clear that the model that predicts the simulta-
neous formation of internal and external complexes between
CB7 and CnTA+ +(n?12) provides a better agreement with
the experimental data.
1H ROESY: To obtain more structural information on the
2:1 complex we performed ROESY measurements. This
technique is especially useful in the characterisation of inter-
molecular interactions, yielding signals from protons that
are close to each other in space even if they are not bonded.
The ROESY experiments therefore yield cross-peaks caused
by through-space dipolar interactions between nuclei and
the observed signal intensity is proportional to the distance
between the nuclei. The ROESY experiments were per-
formed on a sample containing equimolar quantities of
C12TABr and CB7 and another with a large excess of CB7.
An intermolecular ROE cross-peak between the trimethy-
lammonium protons of the surfactant and the methylene
protons of CB7 can be seen in Figure 10 (left). However, it
can be seen that this signal is not present in Figure 10
(right). Takinginto account
these results, we can conclude
that in the 1:1 complex the pos-
itivelychargedammonium
group interacts with one of the
carbonyl-fringed portals. How-
ever, thespectrum of the
sample with a large excess of
CB7 does not contain a signal
due to this interaction.
If in the 2:1 complex the
second molecule of CB7 in-
cludes within the cavity the
alkyl chain that is exposed to
water in the 1:1 complex, one
should observe an increase in
the ROE signal intensity due to
the decrease in the distance be-
tween the head group of the
surfactant and the methylene
protons of the host. The disap-
pearance of this signal can be
explained on the basis of an in-
crease in the distance between
thetrimethylammoniumpro-
tons and the methylene protons
of CB7. This assumption allows
us to suppose that both mole-
cules of CB7 complex with the
head group of the surfactant. The approach of a second CB7
molecule induces the CB7 of the 1:1 complex to move along
the alkyl chain to minimise the repulsions between the por-
tals of the hosts, which results in an increase in the distance
between the head group and the portal of the first host
(Scheme 4).
STD experiments: In an effort to confirm the proposed
structural model represented in Scheme 4 for the 2:1 com-
plexes formed between CB7 and CnTA+ +(n=12 and 14), we
carried out NMR measurements by using the STD techni-
que, which allows the detection and identification of the
region of the guest that is in contact with the host.[27]
The1H NMR spectrum of a sample of 1.3 mm of C12TABr
and 4.5 mm of CB7 recorded at 58 8C is shown in Figure 11
(bottom). The STD spectrum of the same sample when the
signals of CB7 are saturated is shown in Figure 11 (top). Sig-
nals due to the surfactant can be observed in the STD spec-
trum with saturated CB7 signals and this proves the exis-
tence of interactions between the host and the guest.
To obtain accurate information, the dependence of the
STD NMR signal intensity on the duration of saturation was
studied and, from these data, it was possible to construct
STD growth curves. The STD growth curves of the STD sig-
nals when the portal protons of CB7 are saturated are
shown in Figure 12; the intramolecular interactions show in-
tense STD and the intermolecular interaction that is most
relevant is STDC2,8. This indicates that the portal protons Ha
Figure 10.1H ROESY spectra of CB7–C12TABr in D2O. Left: [C12TABr]=1.3 mm and [CB7]=1.3 mm. Right:
[C12TABr]=1.3 mm and [CB7]=4.5 mm.
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of CB7 interact with the protons on C-2 and C-8 of the sur-
factant (Scheme 5).
On the basis of the kinetics,
measurements, we believe that in the 2:1 complex both mol-
ecules of CB7 complex the head group of the surfactant, as
shown in Scheme 4. Because both hosts complex with the
surfactant head group, the approach of a second CB7 mole-
cule causes the CB7 of the 1:1 complex to move along the
alkyl chain to minimise the repulsions between the portals
1H NMR, ROESY and STD
of the hosts. This situation is consistent with the continuous
upfield shift observed for the head group and the decrease
in the downfield shift observed for the terminal carbon pro-
tons, which in the 2:1 complex should be closer to the CB7
portal or less exposed to water.
Results published on the complexation of CB7 with the
monocationic guests Thioflavin T18and Sanguinarine[17]
show the formation of 2:1 complexes, each of which are
formed as an inclusion complex with two CB7 molecules,
with the positive charge of the guest interacting with the
oxygen atoms of the two hosts.
The approach of a second host towards the head group of
the surfactant, to minimise the repulsive forces between the
portal oxygen atoms of the different hosts, leads the host to
form an inclusion complex with the surfactant by moving
along the alkyl chain. The intensity of the repulsive forces
decreases as the hydrocarbon chain of the surfactant moves.
In this way the hydrophobic character of the surfactant has
a significant influence on the magnitude of K2:1.
Conclusion
The results obtained in this study allow us to conclude that
CB7 molecules can form 2:1 complexes with CnTA+ +surfac-
tants. Taken together, the results of the kinetics,
ROESY and STD investigations indicate that in the forma-
tion of the 2:1 complexes, both hosts complex the trimethy-
lammonium group of the surfactant. The binding constants
for the 1:1 complexes are independent of the length of the
alkyl chain of the surfactant, whereas in the 2:1 complexes
there is a relationship between K2:1and the chain length of
the surfactant.
1H NMR,
Acknowledgements
Financial support from the Ministerio de Ciencia y Tecnologia (Project
CBQ2011-22436) and the Xunta de Galicia (PGIDIT10-PXIB209113PR
and 2007/085). M.P. acknowledges the Fundażo para a CiÞncia e Tecno-
logia (FCT) (Portugal) for a Ph.D. grant (Grant SFRH/BD/60911/2009).
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(4.5 mm) recorded at 58 8C. Top: STD spectrum recorded at 58 8C in which
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Figure 12. Normalised intensities of the STD spectrum of CB7 and
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3–6. Bottom: CB7 signals: (&) Hband (*) Hc.
Scheme 5.
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Received: September 28, 2011
Revised: February 22, 2012
Published online: May 13, 2012
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