Static and dynamic behavior of 2:1 inclusion complexes of cyclodextrins and charged porphyrins in aqueous organic media

Article abstract of DOI:10.1021/ja020253n

Two heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TMe-β-CD) molecules strongly include the peripheral substituents at the 5- and 15-positions of the charged meso-tetrasubstituted porphyrins, PorSub₄ [TPPS₄ (Sub = p-C₆H

Full text of DOI:10.1021/ja020253n

Published on Web 07/26/2002
Static and Dynamic Behavior of 2:1 Inclusion Complexes of
Cyclodextrins and Charged Porphyrins in Aqueous
Organic Media
Koji Kano,*,† Ryuhei Nishiyabu,† Takuji Asada,† and Yasuhisa Kuroda‡
Contribution from the Department of Molecular Science and Technology, Faculty of
Engineering, Doshisha UniVersity, Kyotanabe, Kyoto 610-0321, Japan, and Department of
Polymer Science, Kyoto Institute of Technology, Matsugasaki, Kyoto 606-8585, Japan
Received February 20, 2002
Abstract: Two heptakis(2,3,6-tri-O-methyl)-â-cyclodextrin (TMe-â-CD) molecules strongly include the
peripheral substituents at the 5- and 15-positions of the charged meso-tetrasubstituted porphyrins, PorSub4
[TPPS4 (Sub ) p-C6H4-SO3-), TPPOC3PS (p-C6H4-O-(CH2)3-p-C6H4-SO3-), TCPP (Sub ) p-C6H4-CO2-),
and TPPOC3Py (p-C6H4-O-(CH2)3-Py+Br-), where Py+ ) N-alkylpyridinium] in aqueous ethylene glycol.
The binding constants (K1 and K2) and the rate constants (k1 and k2) for formation of the 1:1 and 2:1
complexes of TMe-â-CD and PorSub4 were determined. Both the binding constants and the rate constants
for anionic TPPS4, TCPP, and TPPOC3PS were much larger than those for cationic TPPOC3Py. The
smaller k1 and k2 values for TPPOC3Py indicate a higher barrier for penetration of a cationic guest into the
TMe-â-CD cavity. The methyl groups at the rims and the cavity wall of the host are positively polarized due
to the inductive effect of the ethereal oxygens. The positively polarized rims and interior of the host cavity
should prevent the penetration of the cationic substituent of TPPOC3Py into the TMe-â-CD cavity. The 2:1
TMe-â-CD-PorSub4 complexes are extraordinary stable in aqueous solutions, even in the case of cationic
TPPOC3Py. Formation of both 1:1 and 2:1 complexes is promoted by negative and large enthalpy changes,
suggesting a strong van der Waals interaction as the main binding force.
Introduction
nated TPPOC3A (Table 1). The K values for the 1:1 (K1) and
2:1 complexation processes (K2)
It is expected that cyclodextrin (CD) provides a microscopi-
cally apolar environment around the center of a porphyrin ring
and prevents self-aggregation of the porphyrin if the CD
molecules deeply include the substituents at the meso positions
of the porphyrin. If CDs actually show such a function, they
might act as the simplest apoprotein models. Several studies
have been carried out with interactions of water-soluble por-
phyrins and CDs. Naturally occurring porphyrins such as
deuteroporphyrin IX, hematoporphyrin IX, and coproporphyrin
III, without aryl groups at the meso positions of the porphyrins,
form very weak complexes with γ-CD, having binding constants
(K) of about 16-35 M-1 in water.1 The weak complexation of
these porphyrins is ascribed to the absence of appropriate CD-
binding sites in the porphyrins. In comparison, several synthetic
porphyrins having ionic aryl substituents at the meso positions
have been shown to form relatively stable complexes of CDs
and the porphyrins. Inclusion of the ionic aryl substituents of a
porphyrin by CD was first reported by Manka and Lawrence,2
who found the formation of a trans-type 2:1 complex of
heptakis(2,6-di-O-methyl)-â-CD (2,6-DMe-â-CD) and proto-
K1
Por + CD y
\
K2
z Por-CD
(1)
(2)
Por-CD + CD y\z CD-Por-CD
have been determined by means of absorption spectroscopy in
0.05 M succinic acid buffer at pH 5 and 60 °C to be (7.7 (
0.7) × 104 and (5.9 ( 1.1) × 104 M-1, respectively.3 The result
indicates a strong ability of the O-methylated â-CD to yield
the 2:1. Mosseri et al. studied complexation of anionic metal-
loporphyrins such as Fe(III)TPPS4 and Zn(II)TPPS4 with
â-CD.4,5 Although they reported the 4:1 complexes of â-CD
and metalloporphyrins, the stoichiometry of the complexes needs
be reconsidered.6 The complexation of an anionic porphyrin free
base with native â-CD was examined by Ribo´ et al.7 On the
(3) Dick, D. L.; Rao, T. V. S.; Suckumaran, D.; Lawrence, D. S. J. Am. Chem.
Soc. 1992, 114, 2664-2669.
(4) Mosseri, S.; Mialocq, J. C.; Perly, B.; Hambright, P. J. Phys. Chem. 1991,
95, 4659-4663.
(5) (a) Mosseri, S.; Mialocq, J. C. Radiat. Phys. Chem. 1991, 37, 653-656.
(b) Mosseri, S.; Mialocq, J. C.; Perly, B.; Hambright, P. J. Phys. Chem.
1991, 95, 2196-2203.
(6) We studied the complexation of FeIIITPPS4 with TMe-â-CD and found
the formation of the stable 1:1 and trans-type 2:1 complexes. No 4:1
complex was detected at any pH. Yamada, A.; Kano, K. Presented at the
XI International Symposium on Supramolecular Chemistry, Fukuoka, Japan,
August 2000; Abstract PA-45.
* Address correspondence to this author. E-mail: kkano@mail.
doshisha.ac.jp.
† Doshisha University.
‡ Kyoto Institute of Technology.
(1) Hirai, H.; Toshima, N.; Hayashi, S.; Fujii, Y. Chem. Lett. 1983, 643-646.
(7) Ribo´, J. M.; Farrera, J.-A.; Valero, M. L.; Virgili, A. Tetrahedron 1995,
51, 3705-3712.
(2) Manka, J. S.; Lawrence, D. S. J. Am. Chem. Soc. 1990, 112, 2440-2442.
9
10.1021/ja020253n CCC: $22.00 © 2002 American Chemical Society
J. AM. CHEM. SOC. 2002, 124, 9937-9944
9937

A R T I C L E S
Kano et al.
Table 1. Abbreviations of 5,10,15,20-Tetrasubstituted Porphyrins
center of the porphyrin to provide a microscopically apolar
environment.
Previous studies in this area are mostly qualitative and
speculative. Quantitative investigations on both static and
dynamic behavior of the complexation make it possible to
understand totally the interactions between ionic porphyrins and
CDs. The present study reveals the novel properties of TMe-
â-CD as the host for ionic porphyrins and the mechanism for
extremely strong complexation in such a host-guest system.
Experimental Section
Preparation of Porphyrins. TPPOC2Py and TPPOC3Py (Table 1)
were prepared according to the procedures described in the literature.13
TPPS4, purchased in the protonated form (Tokyo Kasei), was dissolved
in water and passed through a DOWEX HCR-W2 ion-exchange column
(Na form) to obtain the TPPS4 tetrasodium salt. Elemental analysis
indicated the formation of Na4TPPS4‚7H2O. TCPP (Table 1) in the
protonated form (Tokyo Kasei) was dissolved in water and neutralized
with equimolar NaOH. Water was evaporated, and the residue was dried
under vacuum. TPPOC3PS was synthesized as follows. A mixture of
4-(3-bromopropyl)benzenesulfonyl chloride (10 mmol), phenol (8
mmol), and K2CO3 (14.5 mmol) in 100 mL of acetone was stirred for
16 h at room temperature under Ar. The reaction mixture was filtered
to remove K2CO3, and acetone was evaporated from the filtrate. The
residue was dissolved in chloroform and washed with water saturated
with NaCl. The residue obtained after evaporation of the chloroform
was purified by silica gel column chromatography with chloroform-
hexane (3:2) to yield pure phenyl 4-(3-bromopropyl)benzenesulfonate
basis of 1H NMR data, they assumed the formation of a trans-
type 2:1 complex of â-CD and TPPS4 having a structure similar
to that of TPPOC3A. Other research groups, however, reported
the K values for complexation of TPPS4 with â-CD (440-5600
M-1) by assuming a 1:1 complex.8-10 In previous papers,11,12
we reported different behavior of CDs toward cationic and
anionic guests: anionic compounds can penetrate into the
hydrophobic CD cavities, while cationic ones cannot. As partial
confirmation of this model, we presented the apparent pKa values
of the various diprotonated porphyrins in the presence of CDs.
The pKa value of anionic TPPS4 in water (5.4) drastically
decreases upon complexation with heptakis(2,3,6-tri-O-methyl)-
â-CD (TMe-â-CD) (∆pKa ) 5.0), while the effect of â-CD is
much weaker (∆pKa ) 1.2). 1H NMR spectroscopy reveals the
formation of the trans-type 2:1 complex of TMe-â-CD and
TPPS4 in which the secondary OCH3 group sides of the CD
molecules face each other. On the other hand, cationic TMPyP
(Table 1) does not interact with either â-CD or TMe-â-CD at
all (∆pKa ) 0). Another cationic porphyrin, TAPP, shows little
tendency to bind to any CDs. On the basis of these results, the
following model is proposed:
1
(99% yield). The product was identified by H NMR and FAB-MS.
Phenyl 4-(3-bromopropyl)benzenesulfonate (11.3 mmol) was reacted
with 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (0.59 mmol) in 100
mL of DMF containing K2CO3 (39 mmol) with stirring for 3 days under
Ar. After evaporation of DMF, the residue was dissolved in dichlo-
romethane and washed with water saturated with NaCl. The dark purple
solid obtained by evaporation of dichloromethane was purified by silica
gel column chromatography with chloroform-methanol (100:1) to
obtain pure 5,10,15,20-tetrakis{4-[3-(4-phenoxysulfonylphenyl)propoxy]-
phenyl}porphyrin (32% yield). The product was identified by 1H NMR
and FAB-MS. 5,10,15,20-Tetrakis{4-[3-(4-phenoxysulfonylphenyl)-
propoxy]phenyl}porphyrin (22.5 µmol), methanol (5 mL), and 1,4-
dioxane (50 mL) were placed in a flask, and 30 mL of 10 M aqueous
NaOH was added. After being stirred at 60 °C for 48 h, the reaction
mixture was neutralized by addition of 1 M aqueous HCl and dissolved
in 400 mL of water. After the mixture was washed with chloroform,
water was evaporated under reduced pressure, and the residue was
dissolved in methanol. The inorganic salt was removed by filtration.
The solid that precipitated upon addition of acetone was collected by
filtration. Such a desalting procedure was repeated three times, and
the dark brown solid finally obtained was washed with water-acetone
(4:1), to give TPPOC3PS. Anal. Calcd for C80H66N4O16S4Na4: C, 57.62;
H, 4.71; N, 3.36. Found: C, 57.98; H, 4.43; N, 3.41.
(1) The cavities of both â-CD and TMe-â-CD are favorable
for loading anionic porphyrin guests but unfavorable for cationic
ones.
(2) â-CD forms a relatively weak complex with TPPS4.
(3) TMe-â-CD has a strong tendency to include the peripheral
aryl groups of TPPS4, and two TMe-â-CD molecules cover the
Other Materials. TMe-â-CD (Nacalai) was purchased and used as
received. â-CD (Nacalai) was washed with THF using a Soxhlet
extractor to remove the antioxidant and dried.
Spectroscopy. Absorption spectra were recorded on a Shimadzu UV-
1
2100 spectrophotometer. H NMR spectra were taken using a JEOL
JNM-A400 spectrometer (400 MHz). Sodium 3-trimethylsilyl[2,2,3,3-
2H4]propionate (TSP, Aldrich) was used as an external standard. FAB
MS spectra were recorded on a JEOL JMS-700 spectrometer.
Methods. Determination of K1 and K2 values was performed by
measuring the absorption spectral changes of a porphyrin ([Por]0 ) 2
× 10-6 or 2 × 10-5 M) as a function of CD concentration.14 Na2CO3
was used to adjust pH. Titration curves obtained by plotting the changes
(8) Sur, S. K.; Bryant, R. G. J. Phys. Chem. 1995, 99, 4900-4905.
(9) Venema, F.; Nelissen, H. F. M.; Berthault, P.; Birlirakis, N.; Rowan, A.
E.; Feiters, M. C.; Nolte, R. J. M. Chem.-Eur. J. 1998, 4, 2237-2250.
(10) Mosinger, J.; Deumie´, M.; Lang, K.; Kuba´t, P.; Wagnerova´, D. M. J.
Photochem. Photobiol. A 2000, 130, 13-20.
(11) Kano, K.; Tanaka, N.; Minamizono, H.; Kawakita, Y. Chem. Lett. 1996,
925-926.
(12) Kano, K.; Tanaka, N.; Minamizono, H. In Molecular Recognition and
Inclusion; Coleman, A. W., Ed.; Kluwer: Dordrecht, The Netherlands,
1998; pp 191-196.
(13) Schneider, H.-J.; Wang, M. J. Org. Chem. 1994, 59, 7473-7478.
9
9938 J. AM. CHEM. SOC. VOL. 124, NO. 33, 2002

2:1 Inclusion Complexes of CDs and Charged Porphyrins
A R T I C L E S
in optical densities (∆A) at four wavelengths (Q-bands) vs [CD]0 were
analyzed by a nonlinear least-squares method (damping Gauss-Newton
method) using a computer program developed by one of the authors
(Y.K.). The reproducibility of the data was checked by repeating all
experiments at least three times.
The complexation and dissociation rate constants (k1, k2, k-1, and
k-2) were determined by following ∆A after the solutions of CD and
porphyrin were rapidly mixed using a UNISOKU stopped-flow
apparatus with a multichannel photodiode array.
Por + CD yk1z Por-CD
(3)
(4)
k-1
Por-CD + CD yk2z CD-Por-CD
k-2
The data were analyzed by a nonlinear least-squares method (damping
Gauss-Newton method) using the computer program REDAP devel-
oped by Kuroda et al.15 Five time courses, obtained by altering [TMe-
â-CD]0, were fitted by a set of k1, k-1, k2, and k-2 values to heighten
the reliability of this method. The reliability of this method was checked
by another analytical method, kindly offered by Prof. R. Pasternack
(Swarthmore College), where unknown parameters are reduced to three
(k1, k-1, and k2) by assuming [Por] , [TMe-â-CD]. The agreement of
both methods was satisfactory (Supporting Information).
13C spin-lattice relaxation times (T1) were measured for TMe-â-
CD (0.1 M) and a mixture of TMe-â-CD (0.1 M) and TPPS4 (0.05 M)
in D2O under Ar using a JEOL JNM-A400 spectrometer. The
inversion-recovery pulse sequence (180°-t-90°), with a relaxation
delay at least 5 times longer than the longest T1, was employed. The
data were analyzed by curve fitting using a program loaded in the NMR
apparatus. Reproducibility was checked by repeating the experiments
at least three times. The T1 values for TPPS4 alone were measured in
DMSO-d6 because TPPS4 (0.05 M) in D2O aggregates spontaneously.
Figure 1. 1H NMR spectra of TPPS4 (1.0 × 10-3 M) in D2O at 25 °C in
the absence and in the presence of various amounts of TMe-â-CD.
Results
1
1H NMR Spectroscopy. The H NMR spectral changes of
TPPS4 (1 × 10-3 M) were measured in D2O as a function of
[TMe-â-CD]0, and the results are shown in Figure 1. TPPS4
has been known to aggregate spontaneously in aqueous solution
at high concentration and/or in the presence of inorganic salt.16
As shown in Figure 1, the signal due to the ortho protons (Ho)
of TPPS4 (1 × 10-3 M) is broadened in D2O without TMe-â-
CD, while that due to the meta protons (Hm) appears as a sharp
doublet. The broadening of Ho is ascribed to self-aggregation
of TPPS4. New 1H NMR signals appear upon addition of TMe-
â-CD, and the growth of the signals levels off at [TMe-â-CD]0
) 2 × 10-3 M. The NMR spectrum is composed of two sets of
the signals due to TPPS4 complexed with TMe-â-CD. The
assignment of each signal was achieved by measuring H-H
COSY and ROESY spectra of the TPPS4-TMe-â-CD complex
1
(Supporting Information). The H NMR spectrum also reveals
the formation of the trans-type 2:1 complex of TMe-â-CD and
TPPS4. Other types of complexes cannot explain such a simple
1H NMR spectrum.
Figure 2. 1H NMR spectra of TPPOC3PS (1.0 × 10-3 M) in D2O at 25
°C in the absence and in the presence of various amounts of TMe-â-CD.
“i” represents the protons inside the CD cavity.
(14) (a) Conners, K. A. Binding Constants. The Measurement of Molecular
Complex Stability; John Wiley & Sons: New York, 1987; Chapter 4. (b)
Kano, K.; Hasegawa, H. J. Am. Chem. Soc. 2001, 123, 10616-10627.
(15) Kuroda, Y.; Kawashima, A.; Ogoshi, H. Chem. Lett. 1996, 57-58. The
REDAP program may be obtained by request from Kuroda (e-mail:
ykuroda@ipc.kit.ac.jp).
(16) (a) Pasternack, R. F.; Huber, P. R.; Boyd, P.; Engasser, G.; Francesconi,
L.; Gibbs, E.; Fasella, P.; Venturo, G. C.; Hinds, L. deC. J. Am. Chem.
Soc. 1972, 94, 4511-4517. (b) Corsini, A.; Herrmann, O. Talanta 1986,
33, 335-339.
In the case of TPPOC3PS (Figure 2), two sets of signals due
to two phenyl rings in the free and included forms were observed
with TPPOC3PS until two equivalent amounts of TMe-â-CD
were added, though splits of the signals of Hm and Him, Ho′
and Hio′, and Hm′ and Him′ (where “i” indicates the proton
belonging to the group included in the CD cavity) were very
9
J. AM. CHEM. SOC. VOL. 124, NO. 33, 2002 9939

A R T I C L E S
Kano et al.
Table 2. Binding Constants for Complexation of Charged
Porphyrins with TMe-â-CD in Various Solvents at 25 °C
porphyrin
TPPS4
TPPS4
TPPOC3PS EG
TPPOC3PS CH3OH
TPPOC3PS DMSO
solventa
K /M-1
K /M-1
2
1
EG-H2O (3:1) (2.0 ( 1.3) × 104 (5.8 ( 1.5) × 104
EG
0
0
(8.7 ( 2.2) × 103 (9.1 ( 1.3) × 104
(2.9 ( 0.9) × 102 (2.9 ( 0.2) × 102
0
0
TCPP
EG-H2O (3:1) (1.7 ( 1.4) × 104 (2.0 ( 1.1) × 105
EG-H2O (1:1) (4.6 ( 2.4) × 104 (4.4 ( 1.6) × 105
EG-H2O (3:1) (2.3 ( 0.9) × 103 (9.4 ( 0.2) × 103
TPPOC3Py
TPPOC3Py
TPPOC3Py
EG
0
0
a The K values for complexation of TPPS4 in H2O and EG-H2O (1:1),
TPPOC3PS in H2O, EG-H2O (1:1), and EG-H2O (3:1), TCPP in H2O
and EG-H2O (1:1), and TPPOC3Py in glycerol-H2O (1:1) were not
determined because the K1K2 values were too large.
example. Regular changes with seven isosbestic points were
observed. Other porphyrin-TMe-â-CD systems show similar
spectral changes. The titration curves obtained are shown in
the inset of Figure 3, where the four titration curves plotted at
different wavelengths were fitted with a set of K1 and K2 values.
The titration curves for all systems studied here were not fitted
with an equation for 1:1 complexation but were well fitted with
the equation for 2:1 complex formation. The binding constants
obtained are summarized in Table 2. To the best of our
knowledge, only one example has been reported of the K1 and
K2 values for complexation of porphyrin with CD. Dick et al.
reported the K1 and K2 values for complexation of TPPOC3A
and 2,6-DMe-â-CD to be (7.7 ( 0.7) × 104 and (5.9 ( 1.1) ×
104 M-1, respectively, in water at pH 5.0 and 60 °C.3 The results
obtained here in EG-H2O (3:1) make possible a comparison
of the binding behavior of cationic TPPOC3Py with that of
anionic porphyrins. Both the K1 and K2 values for the anionic
porphyrins (TPPS4, TCPP, and TPPOC3PS) are much larger
than those for cationic TPPOC3Py. The binding constants for
the TPPOC3PS-TMe-â-CD complex were too large to be
determined, even in EG-H2O (3:1). Previously, we found that
cationic TMPyP and TAPP scarcely interact with TMe-â-
CD.11,12 Judging from these results, we can conclude that the
stability of cationic porphyrin-TMe-â-CD complexes is lower
than that of anionic porphyrin complexes. Comparing the results
for TPPS4 with those for TPPOC3PS, it can be concluded that
the complex of TPPC3PS having the amphiphilic peripheries
is much more stable than that of TPPS4 having more hydrophilic
peripheries. TPPOC3PS forms the trans-type 2:1 complex, even
in neat EG (dielectric constant ꢀ ) 37.7) and methanol (ꢀ )
32.63), but not in DMSO (ꢀ ) 46.6).
The complexation of TPPS4 with native â-CD in water was
also examined. Previous studies reported the binding constants
for the 1:1 complex of â-CD and TPPS4.8-10 The absorption
spectral changes of TPPS4 in water upon addition of â-CD were
measured (Supporting Information). Under the present condi-
tions ([TPPS4] ) 2 × 10-6 M), TPPS4 does not aggregate
spontaneously. At higher â-CD concentrations, deviation from
an isosbestic point was observed, clearly indicating simultaneous
formation of the 1:1 complex and a complex having a stoichi-
ometry other than 1:1. The titration curves for this system were
fit well with the equations for 2:1 complexation. The K1 and
K2 values in water (but not in aqueous EG) at 25 °C are (1.7 (
0.3) × 104 and (2.3 ( 0.4) × 103 M-1, respectively. The K1
value is considerably larger than the reported values, which have
been evaluated assuming formation of only the 1:1 complex.8-10
Figure 3. Absorption spectra of TPPOC3Py (2.0 × 10-5 M) in EG-H2O
(3:1) containing various amounts of TMe-â-CD at 25 °C. Inset: Changes
in absorbances (∆A) of TPPOC3Py (2.0 × 10-5 M) upon addition of TMe-
â-CD in EG-H2O (3:1) at 25 °C. The solid lines are the best fit to an
equation for the 1:1 and 1:2 equilibria: K1 ) 2300 ( 900 M-1, K2 ) 9400
( 200 M-1
.
small. Since no signals were observed for free TPPOC3PS
because of self-aggregation, the 1H NMR spectrum of the por-
phyrin in the presence of 2 × 10-3 M TMe-â-CD is ascribed
to the 2:1 complex. At [TMe-â-CD]0 > 2 × 10-3 M, the signals
due to the terminal phenyl rings (Ho′ and Hm′) as well as the
meta protons of the inner ones (Hm) of TPPOC3PS start to split,
again yielding two sets of clearly separated signals (Hm-Him,
Ho′-Hm′, and Hio′-Him′). Such marked splitting seems to be
due to formation of 3:1 and/or 4:1 complexes of TMe-â-CD
and TPPOC3PS. The ROESY spectrum of the 2:1 complex of
TMe-â-CD and TPPOC3PS (Supporting Information) shows the
strong cross-peaks between Hio of the guest and the protons at
the 3- (H-3) and 5-positions of the host (H-5) and Him of the
guest and H-5 of the host. The TMe-â-CD molecules of the
2:1 complex penetrate deeply to cover the center of the
porphyrin ring.
Meanwhile, the formation of only the trans-type 2:1 complex
of TMe-â-CD and TPPOC3Py was verified by means of NMR
spectroscopy (Supporting Information). Self-aggregation of this
porphyrin has been studied previously.17 Upon addition of TMe-
â-CD, the higher self-aggregates were dissociated to the
TPPOC3Py monomer by forming the trans-type 2:1 complex.
Binding Constants. The K values for complexation of all
charged porphyrins with TMe-â-CD in water were too large to
be determined. In all cases, the absorption spectral changes of
the porphyrins were saturated at 2 equiv concentration of TMe-
â-CD, indicating the formation of the extremely stable 2:1
complexes of TMe-â-CD and the porphyrins in water. We then
employed aqueous organic solvents to reduce the K values.
Under the present conditions for measuring absorption spectra,
Beer-Lambert’s law was maintained with all porphyrins used
in aqueous organic solvents without CD, even in pure water.
Therefore, self-aggregation of the porphyrins need not be
considered. The absorption spectral changes of TPPOC3Py in
75% (v/v) ethylene glycol (EG)-25% H2O (EG-H2O (3:1))
upon addition of TMe-â-CD are shown in Figure 3 as a typical
(17) Kano, K.; Fukuda, K.; Wakami, H.; Nishiyabu, R.; Pasternack, R. F. J.
Am. Chem. Soc. 2000, 122, 7494-7502.
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2:1 Inclusion Complexes of CDs and Charged Porphyrins
A R T I C L E S
Figure 4. Change in rotational freedom of the peripheral substituents of TPPOC3Py upon complexation with TMe-â-CD.
Table 3. Rate Constants for Formation and Dissociation of 1:1 and 2:1 Complexes of TMe-â-CD and Charged Porphyrins in Aqueous EG
at 25 °C
porphyrin
solvent
k1/M-1 s-1
k-1/s-1
k2/M-1 s-1
k-2/s-1
TPPS4
EG-H2O (3:1)
EG-H2O (3:1)
EG-H2O (1:1)
EG-H2O (3:1)
EG-H2O (1:1)
(3.0 ( 0.9) × 104
(1.8 ( 0.1) × 105
(1.3 ( 0.1) × 104
(8.7 ( 0.2) × 103
(1.1 ( 0.1) × 104
4.6 ( 0.1
(5.3 ( 0.4) × 104
(3.9 ( 0.1) × 104
(3.6 ( 0.1) × 103
(1.9 ( 0.1) × 103
(3.7 ( 0.1) × 103
0.43 ( 0.01
TPPOC3PS
TPPOC3Py
TPPOC3Py
TPPOC2Py
0.24 ( 0.01
0.41 ( 0.01
3.9 ( 0.1
(4.8 ( 0.3) × 10-3
(2.6 ( 0.1) × 10-2
0.16 ( 0.01
0.35 ( 0.01
(3.2 ( 0.5) × 10-2
Table 4. Thermodynamic Parameters for Complexation of TPPS4 and TPPOC3Py with CDs
1:1 complex
2:1 complex
system
solvent
∆H°/kJ mol-1
∆S°/J mol-1 K-1
∆H°/kJ mol-1
∆S°/J mol-1 K-1
TPPS4/TMe-â-CD
EG-H2O (3:1)
H2O
EG
EG-H2O (1:1)
EG-H2O (3:1)
DMSO-H2O (1:1)
-61 ( 9
10 ( 4
-40 ( 4
-72 ( 9
-44 ( 2
-77 ( 4
-121 ( 29
119 ( 13
-46 ( 4
-5 ( 1
-37 ( 2
-35 ( 6
-25 ( 2
-42 ( 4
-62 ( 12
48 ( 3
TPPS4/â-CD
TPPOC3PS/TMe-â-CD
TPPOC3Py/TMe-â-CD
TPPOC3Py/TMe-â-CD
TPPOC3Py/TMe-â-CD
-50 ( 12
-152 ( 32
-86 ( 6
-31 ( 5
-9 ( 20
-9 ( 7
-171 ( 12
-39 ( 13
No complex was formed in EG-H2O (1:1). The ability of â-CD
to form a complex with TPPS4 is much weaker than that of
TMe-â-CD.
large enthalpy changes (∆H°) promote the 1:1 and 2:1 com-
plexation, while the negative entropy changes (∆S°) suppress
the complexation. A large entropy loss was observed, especially
for 1:1 complex formation. Essentially the same patterns were
obtained for the case of TPPOC3Py. The thermodynamic
parameters for the complexation of TPPOC3Py with TMe-â-
CD in EG-H2O (1:1) are studied here for comparison. The first
step, formation of the 1:1 complex, is associated with negative
and large ∆H° and ∆S°, while ∆S° dramatically increases in
the second complexation, formation of the 2:1 complex.
Rotational motion of three peripheral substituents seems to be
seriously restricted when a TMe-â-CD molecule includes a
p-C6H4-O-(CH2)3-Py+ group (Figure 4), yielding a negative and
large ∆S°. Meanwhile, the second complexation, formation of
the 2:1 complex, does not lead to a major reduction in the
motional freedom of the 1:1 CD-porphyrin complex. This
might be the reason for the negative but small ∆S° in the second
step. Essentially the same discussion can be applied for the other
systems, except for TPPS4-â-CD. Thermodynamic patterns for
complexation of TPPS4 with native â-CD in water are com-
pletely different from those with TMe-â-CD. The first com-
plexation of TPPS4 with â-CD is promoted by the positive and
large ∆S°. Here ∆H° is positive. The second step of complex-
ation is also dominated by the entropy term. There are several
examples of CD complex formation which are accompanied by
positive ∆S° values.18,19 Dehydration from host and/or guest
upon complexation has been assumed as a main reason for the
positive ∆S°.18,20 Since both primary and secondary OH groups
of â-CD are solvated by water, extensive dehydration from both
rims of the â-CD cavity should occur when a peripheral
substituent of the guest penetrates into the CD cavity. Dehydra-
Kinetics. To further probe the basis for a cavity of CD being
favorable for loading an anionic guest but unfavorable for a
cationic one, rate constants for the forward and backward
processes (eqs 3 and 4) were determined. The time courses of
the optical density changes (∆A) of a porphyrin after mixing
with various amounts of TMe-â-CD were fitted by a set of k1,
k-1, k2, and k-2 values (Supporting Information). The results
are listed in Table 3. The k1 values for the anionic porphyrins
(TPPS4 and TPPOC3PS) are much larger than those for the
cationic ones (TPPOC3Py and TPPOC2Py) under similar
solvent conditions. This result verifies our previous conclusion
that the CD cavity is more favorable for loading an anionic
guest than a cationic one.11,12 Comparison of the data obtained
for TPPOC3Py with those for TPPOC3PS is the best way to
determine the difference in complexation between cationic and
anionic porphyrins. The k1 value for TPPOC3PS in EG-H2O
(3:1) is ca. 20 times larger than that for TPPOC3Py, while the
k-1 value for TPPOC3PS is ca. 16 times smaller than that for
TPPOC3Py. Therefore, the stability constant for the 1:1 complex
of TPPOC3PS is over 300 times larger than that for TPPOC3Py
in EG-H2O (3:1). The K1 and K2 values evaluated from the
rate constants are in agreement with those obtained from the
spectral titrations, within the range of the experimental error.
Thermodynamics. Thermodynamic parameters provide fur-
ther insight into the charge discrimination for complexation by
CDs. The thermodynamic parameters for the present systems
were determined from the van’t Hoff plots (Supporting Informa-
tion). The results are listed in Table 4. In the complexation of
TPPS4 with TMe-â-CD in EG-H2O (3:1), the negative and
(18) Rekharsky, M. V.; Inoue, Y. Chem. ReV. 1998, 98, 1875-1917.
9
J. AM. CHEM. SOC. VOL. 124, NO. 33, 2002 9941

A R T I C L E S
Kano et al.
Figure 5. 13C NMR spectra of TMe-â-CD (0.1 M) in D2O at 25 °C in the
absence and in the presence of various amounts of TPPS4. “C-n” denotes
the 13C nucleus of TMe-â-CD at the n-position.
Figure 6. Complexation-induced chemical shift changes (∆δ ) δfree
-
δ
obs) of the 13C nuclei of (a) TMe-â-CD and (b) â-CD complexed with
TPPS4 in D2O: (a) [TPPS4]0/[TMe-â-CD]0 ) 0.05 M/0.1 M; (b) [TPPS4]0/
[â-CD]0 ) 0.08 M/0.01 M.
tion also occurs from the charged guest. Therefore, it is quite
reasonable to assume that a positive ∆S° is ascribed to the
increase in freedom of the system due to desolvation from both
â-CD and TPPS4 upon complexation. Of course, dehydration
from both host and guest also occurs in complexation of TMe-
â-CD. Strong van der Waals interactions between guest and
TMe-â-CD seem to hide the contribution of dehydration to the
thermodynamic parameters.
aqueous solution, per-O-methylated CDs such as TMe-R- and
TMe-â-CDs are more flexible than native CDs such as R- and
â-CDs because of the absence of intramolecular hydrogen
bonds.21 Therefore, per-O-methylated CDs change their con-
formations upon inclusion of guests (induced-fit-type complex-
ation).21 It has been known that the signals due to C-1 and C-4
of TMe-â-CD shift most markedly upon inclusion of a guest.22
In complexation with TPPS4, TMe-â-CD changes its conforma-
tion to optimize the intermolecular interactions. Complexation-
induced chemical shift changes (CIS, ∆δ) of native â-CD are
shown in Figure 6, together with those of TMe-â-CD. All 13C
signals of â-CD are scarcely affected by TPPS4, suggesting that
the structure of â-CD is hardly altered upon complexation with
TPPS4. The structure of â-CD is stabilized by the intramolecular
hydrogen bonding between the secondary OH groups at the
2-positions and at the 3-positions of adjacent glucopyranose
units.23
13C NMR Spectroscopy and 13C Spin-Lattice Relaxation
Times. To study the dynamic behavior of complexation of the
2:1 complex of TMe-â-CD and TPPS4, 13C NMR spectra and
13C spin-lattice relaxation times (T1) were measured. The 13
C
NMR spectral changes of TMe-â-CD (0.1 M) were taken in
D2O as a function of [TPPS4]0, and the results are shown in Fi-
1
gure 5. Each signal was assigned by H-13C COSY and CO-
LOC (correlation spectroscopy via long-range coupling spec-
trum). At [TPPS4]0 < 0.05 M ([TMe-â-CD]0/[TPPS4]0 < 2.0),
13C signals due to bound and free TMe-â-CD were detected
independently. At [TPPS4]0 ) 0.05 M ([TMe-â-CD]0/[TPPS4]0
) 2.0), all signals were ascribed to the 2:1 complex of TMe-
â-CD and TPPS4. The signals due to the 13C nuclei at the 1-
and 4-positions (C-1 and C-4, respectively) markedly shift to
lower magnetic fields upon complexation with TPPS4. In
The T1 values of the 13C nuclei of TMe-â-CD were de-
termined by an inversion-recovery method. The inversion-
recovery pattern (Supporting Information) was analyzed to
obtain a T1 value for each 13C nucleus. The results are listed in
(21) (a) Harata, K.; Uekama, K.; Otagiri, M.; Hirayama, F. J. Inclusion Phenom.
1984, 2, 583-594. (b) Harata, K.; Uekama, K.; Otagiri, M.; Hirayama, F.
Bull. Chem. Soc. Jpn. 1987, 60, 497-502. (c) Harata, K.; Tsuda, K.;
Uekama, K.; Otagiri, M.; Hirayama, F. J. Inclusion Phenom. 1988, 6, 135-
142. (d) Kano, K.; Ishimura, T.; Negi, S. J. Inclusion Phenom. Mol.
Recognit. 1995, 22, 285-298. (e) Black, D. R.; Parker, C. G.; Zimmerman,
S. S.; Lee, M. L. J. Comput. Chem. 1996, 17, 931-939. (f) Botsi, A.;
Perly, B.; Hadjoudis, E. J. Chem. Soc., Perkin Trans. 2 1997, 89-94.
(22) Botsi, A.; Yannakopoulou, K.; Perly, B.; Hadjoudis, E. J. Org. Chem. 1995,
60, 4017-4023.
(23) (a) Saenger, W. Angew. Chem. 1980, 92, 343-361. (b) Chacko, K. K.;
Saenger, W. J. Am. Chem. Soc. 1981, 103, 1708-1715. (c) Steiner, T,;
Mason, S. A.; Saenger, W. J. Am. Chem. Soc. 1990, 112, 6184-6190. (d)
Harata, K. Chem. Lett. 1984, 641-644.
(19) (a) Lewis, E. A.; Hansen, L. D. J. Chem. Soc., Perkin Trans. 2 1973, 2081-
2085. (b) Halle´n, D.; Scho¨n, A.; Shehatta, I.; Wadso¨, I. J. Chem. Soc.,
Faraday Trans. 1992, 88, 2859-2863. (c) Inoue, Y.; Hakushi, T.; Liu, Y.;
Tong, L.-H.; Shen, B.-J.; Jin, D.-S. J. Am. Chem. Soc. 1993, 115, 475-
481. (d) Inoue, Y.; Liu, Y.; Tong, L.-H.; Shen, B.-J.; Jin, D.-S. J. Am.
Chem. Soc. 1993, 115, 10637-10644. (e) Ru¨diger, V.; Eliseev, A.; Simova,
S.; Schneider, H.-J.; Blandamer, M. J.; Cullis, P. M.; Meyer, A. J. J. Chem.
Soc., Perkin Trans. 2 1996, 2119-2123. (f) God´ınez, L. A.; Schwartz, L.;
Criss, C. M.; Kaifer, A. E. J. Phys. Chem. B 1997, 101, 3376-3380. (g)
Ross, P. D.; Yamashoji, Y.; Inoue, Y. J. Phys. Chem. B 1997, 101, 87-
100.
(20) Kano, K.; Kitae, T.; Shimofuri, Y.; Tanaka, N.; Mineta, Y. Chem.-Eur. J.
2000, 6, 2705-2713.
9
9942 J. AM. CHEM. SOC. VOL. 124, NO. 33, 2002

2:1 Inclusion Complexes of CDs and Charged Porphyrins
A R T I C L E S
Table 5. 13C Spin-Lattice Relaxation Times (NT1) of TMe-â-CD (0.1 M) in D2O in the Absence and in the Presence of TPPS4 and
ZnTPPS4 (0.05 M) at 25 °C
NT /s
1
system
C-1
C-2
C-3
C-4
C-5
C-6
C-2Me
C-3Me
C-6Me
TMe-â-CD
0.20
0.19
0.20
0.21
0.19
0.20
0.21
0.20
0.21
0.20
0.18
0.19
0.20
0.20
0.20
0.24
0.22
0.23
2.49
2.73
2.70
2.13
1.92
2.06
2.58
2.55
2.61
TMe-â-CD/TPPS4
TMe-â-CD/ZnTPPS4
Table 6. 13C Spin-Lattice Relaxation Times (NT1) of TPPS4 and
ZnTPPS4 (0.05 M) in DMSO-d6 and Those of TPPS4 and
ZnTPPS4 (0.05 M) in D2O in the Presence of TMe-â-CD (0.1 M) at
25 °C
Discussion
The motivating interest in this work is the mechanism for
interactions of charged guests with neutral CD hosts. There are
several examples of inclusion of anionic guests to hydrophobic
CD cavities.25 In contrast, inclusion of cationic guests into CD
cavities is scarcely known. A few studies26-29 on inclusion of
cationic guests into CD cavities suggest that a cationic guest
can slip through a hydrophobic CD cavity to form pseudoro-
taxane, if the final inclusion complex is thermodynamically
stable. Concerning the interactions of porphyrins having cationic
peripheries with CD, Manka and Lawrence2 reported first the
2:1 rotaxane-type complex of TPPOC3A and 2,6-DMe-â-CD
in aqueous solution. In all of these cases, the cationic parts of
the guests are located at the outside of the CD cavities. We
found previously that TMPyP and TAPP, whose cationic
peripheries are attached directly to the porphyrin ring, form very
unstable complexes with any CD, though a corresponding
anionic guest, TPPS4, forms a very stable 2:1 complex with
TMe-â-CD.11,12 The TMe-â-CD-TPPS4 complex is so stable that
the formation of this 2:1 complex can be detected by means of
MALDI-TOF MS (Supporting Information). These results
suggest that the inside of a CD cavity is favorable for loading
anionic guests but not for cationic ones. To generalize this
feature of CD, we studied the interactions of cationic porphyrins
having an ability to form pseudorotaxanes with CD in more
detail. To the best of our knowledge, only one example has
been reported with kinetics on complexation of ionic guests with
CD, which shows that multicationic groups at the ends of a
guest decelerate penetration of the guest into the â-CD cavity
because of a repulsive interaction between the host and the
guest.29 Kinetic study will certainly provide definite evidence
for ion selectivity of CD.
NT /s
1
o
âpy
system
C
Co
Cm
Cm
C
Câpy
i
i
i
TPPS4/DMSO-d6
0.19
0.15
0.21
0.15
0.20
0.15
0.21
0.16
TPPS4/TMe-â-CD
ZnTPPS4/DMSO-d6
ZnTPPS4/TMe-â-CD
0.17
0.19
0.17
0.18
0.15
0.15
0.16
Table 5 as NT1 values, where N is the number of directly
attached hydrogens. In the absence of TPPS4, the NT1 values
of the 13C nuclei (C-1-C-5) which are the components of the
glucopyranose ring are almost constant (0.20-0.21 s). The NT1
value of C-6 is larger than those of other nuclei because C-6 is
the methylene carbon attached to the glucopyranose ring and
has more freedom of motion as compared with the ring carbons.
Upon complexation with TPPS4, the NT1 values of all carbon
nuclei except for the methyl carbon at the 2-position (C-2Me)
become smaller than those of TMe-â-CD alone. Although the
changes in the NT1 values are small, it may be concluded that
the fluctuating motion of TMe-â-CD is reduced upon complex-
ation with TPPS4.
The T1 values of TPPS4 were also determined, and the results
are summarized in Table 6. To observe the pyrrole â-carbon,
the zinc(II) complex of TPPS4 (ZnTPPS4) was also used as the
guest.24 The signal of the pyrrole â-carbons of free base TPPS4
is broadened because of tautomerism of the deuteriums attached
to the pyrrole nitrogens. Since both TPPS4 and ZnTPPS4
aggregate spontaneously in D2O at high concentration, the
measurements of the relaxation times of these porphyrins were
carried out in DMSO-d6, which is more viscous than D2O. The
NT1 values of the phenyl carbons of TPPS4 and ZnTPPS4
significantly decrease upon complexation with TMe-â-CD,
suggesting that the rotational motion of the peripheral substit-
uents is strictly restricted by inclusion. The NT1 values of the
carbons of the phenyl rings (Co and Cm) which are located at
the outside of the CD cavity are smaller than those of the phenyl
rings (Cio and Cim) included in the CD cavity. There may be
some probability of rotation for the phenyl rings included in
the CD cavities, though the rotation of the phenyl rings
sandwiched between two CD molecules is strictly inhibited. The
NT1 values of Co and Cm of TPPS4 and ZnTPPS4 are 0.15-
0.16 s, which are the same as the NT1 values of the â-carbons
of pyrroles (Câpy and Ciâpy). The relaxation times of â-pyrrole
reflect the motion of the whole complex. Therefore, it can be
concluded that the rotational motion of the phenyl rings
sandwiched by the CD molecules is completely restricted.
Since the K values for complexation of the porphyrins used
in this study with TMe-â-CD in water were too large to be
determined, the measurements were carried out in aqueous EG
solutions. In the same solvent, the K1 and K2 values as well as
the k1 and k2 values for the anionic porphyrins are much larger
than those for the cationic ones. Both the k1 and k2 values for
(25) For example, see: (a) Van Etten, R. L.; Sebastian, J. F.; Clowes, G. A.;
Bender, M. L. J. Am. Chem. Soc. 1967, 89, 3242-3253. (b) Bergeron, R.
J.; Channing, M. A.; Gibeily, G. J.; Pillor, D. M. J. Am. Chem. Soc. 1977,
99, 5146-5151. (c) Bergeron, R. J.; Channing, M. A.; McGovern, K. A.
J. Am. Chem. Soc. 1978, 100, 2878-2883. (d) Gelb, R. I.; Schwartz, L.
M.; Cardelino, B.; Fuhrman, H. S.; Johnson, R. F.; Laufer, D. A. J. Am.
Chem. Soc. 1981, 103, 1750-1757. (e) Gelb, R. I.; Schwartz, L. M.; Radeos,
M.; Laufer, D. A. J. Phys. Chem. 1983, 87, 3349-3354. (f) Eftink, M. R.;
Andy, M. L.; Bystrom, K.; Perlmutter, H. D.; Kristol, D. S. J. Am. Chem.
Soc. 1989, 111, 6765-6772. (g) Kano, K.; Mori, K.; Uno, B.; Goto, M.;
Kubota, T. J. Am. Chem. Soc. 1990, 112, 8645-8649.
(26) Matsue, T.; Kato, T.; Akiba, U.; Osa, T. Chem. Lett. 1985, 1825-1828.
(27) (a) Yonemura, H.; Saito, H.; Matsushima, S.; Nakamura, H.; Matsuo, T.
Tetrahedron Lett. 1989, 30, 3143-3146. (b) Saito, H.; Yonemura, H.;
Nakamura, H.; Matsuo, T. Chem. Lett. 1990, 535-538. (c) Yonemura, H.;
Kasahara, M.; Saito, H.; Nakamura, H.; Matsuo, T. J. Phys. Chem. 1992,
96, 5766-5770.
(28) Herrmann, W.; Keller, B.; Wenz, G. Macromolecules 1997, 30, 4966-
4972.
(29) Kawaguchi, Y.; Harada, A. J. Am. Chem. Soc. 2000, 122, 3797-3798.
(24) ZnTPPS4 also formed a very stable 2:1 complex with TMe-â-CD, and the
K1 and K2 values in EG-H2O (3:1) were (8.2 ( 4.3) × 103 and (9.2 (
1.7) × 103 M-1, respectively.
9
J. AM. CHEM. SOC. VOL. 124, NO. 33, 2002 9943

A R T I C L E S
Kano et al.
cationic TPPOC3Py in EG-H2O (3:1) are over 1 order of
magnitude smaller than those for anionic TPPS4 and TPPOC3PS.
These results clearly reveal that an anionic guest penetrates into
the CD cavity more easily than does a cationic guest. What is
the reason for such a difference in inclusion phenomena between
anionic and cationic guests?
The phenyl rings attached directly to the porphyrin ring are
very important for stabilizing the complexes. All porphyrins
which form stable TMe-â-CD complexes have such phenyl
rings. Meanwhile, no complexes are formed in the cases of
PC3Py and PC7Py (Table 1), whose meso positions are
substituted by the alkyl groups with the pyridinium moiety at
the terminals. The alkyl groups are too small to provide effective
van der Waals contacts.32 The effect of guest structure on
complexation as well as the thermodynamic parameters clearly
suggests strong van der Waals interactions between the host
and the guest as the essential force for forming stable inclusion
complexes. Diederich et al. proposed a mechanism for strong
van der Waals interactions in aqueous solution.33 The effects
of EG on reduction in K value may be explained by Diederich’s
mechanism.
Solvation to a guest molecule may affect the rate of
complexation. If cationic TPPOC3Py is solvated by the H2O
and/or EG molecules more strongly than anionic TPPS4 or
TPPOC3PS, the complexation of this cationic guest should
proceed more slowly. However, it is unlikely. The energy
required for desolvation from TPPS4 or TPPOC3PS should be
-
larger than that from TPPOC3Py, because the SO3 group in
the anionic porphyrin is hydrated strongly through the hydrogen-
bonding interaction.30 We have to consider another mechanism.
An answer may be derived by considering the microscopic
polarity of the CD cavity. The electronegative oxygen atoms
are regularly arranged at the upper and lower rims of the CD
cavity. Since the numbers of the oxygen atoms on the primary
OCH3 group side (upper side) and on the secondary OCH3 group
side (lower side) of TMe-â-CD are 7 and 14, respectively, the
inside of the CD cavity as well as the methyl groups at the
rims seems to be polarized positively via an inductive effect.
Mulliken’s population obtained from the MOPAC calculation
supports this assumption (Supporting Information). The nega-
tively polarized charges on the ethereal oxygens at the rims of
the CD cavity may be dispersed through hydrogen bonding with
the water and/or EG molecules. Therefore, an anionic guest can
penetrate into the positively polarized CD cavity. Meanwhile,
the positively polarized rims and interior of the TMe-â-CD
cavity may act as a barrier for penetration of a cationic guest.
None of the porphyrins examined in the present study form
complexes with TMe-â-CD in DMSO, though a relatively stable
2:1 complex with TPPOC3PS is formed in neat EG or methanol.
Since no hydrogen bonds are formed between DMSO and TMe-
â-CD, the anionic guest may be repelled by the negatively
polarized rims of the CD cavity. It has been shown that 5,15-
diphenylpoprhyrin, a neutral porphyrin, forms a trans-type 2:1
complex with 2,6-DMe-â-CD in DMSO.31 It can be considered,
therefore, that protic polar solvents such as H2O, EG, and
methanol play an important role in reducing the electrostatic
repulsion between negatively charged guests and CD.
The thermodynamic parameters for complexation of TPPS4
with native â-CD in water are completely different from those
for complexation with TMe-â-CD. Namely, both of the com-
plexation processes are driven by the positive ∆S° values. There
are several examples of entropically dominated complexation
of anionic guests with neutral or cationic CDs.18-20 Such
phenomena are explained by dehydration from both host and
guest upon complexation, yielding an entropic gain.18,20 Benz
and co-workers measured the negative and large ∆H° and
relatively small but positive T∆S° for complexation of ionene-
6,10 with R-CD. They claimed the participation of hydrophobic
interactions in complexation.28 If classic hydrophobic interac-
tions contribute to the present complexation, then positive ∆S°
should also be observed in the complexation of TMe-â-CD,
which is more hydrophobic than â-CD. The dehydration from
â-CD seems to play an important role in the present system.
Such a drastic difference in thermodynamics between â-CD and
TMe-â-CD causes the difference in inclusion phenomena of
charged porphyrins and CDs.
Acknowledgment. This work was supported by a subsidy to
RCAST of Doshisha University from the Ministry of Education,
Science, Sports and Culture, Japan. We thank Professor Robert
F. Pasternack at Swarthmore College for his encouragement and
stimulating discussion. We also thank Dr. Kazuhiko Ibuki at
Doshisha University for the helpful suggestions about determi-
nation of binding constants.
In all of the complexation processes of TMe-â-CD, both ∆H°
and ∆S° show negative values. The thermodynamic data indicate
the absence of participation of classic hydrophobic interactions
in complexation. The negative and large ∆H° values can be
interpreted in terms of the strong van der Waals interactions
between host and guest. The larger ∆S° value for the second
complexation step compared with that for the first step suggests
that the reduction in the freedom of rotational motion in the
first step is more serious than that in the second step. The
restriction of rotational motion of the peripheral substituents of
TPPS4 upon complexation with TMe-â-CD is confirmed from
the 13C spin-lattice relaxation times. It is interesting that the
rotational motion of the sulfonatophenyl groups sandwiched by
two CD cavities is restricted more seriously than the rotational
motion of those included by TMe-â-CD (Table 6).
Supporting Information Available: ROESY spectra of the
TMe-â-CD-TPPS4 complex, 1H NMR spectral changes of
TMe-â-CD upon complexation with TPPS4, van’t Hoff plots
for determination of ∆H° and ∆S° for the TPPOC3Py-TMe-
â-CD system, the inversion-recovery pattern for determination
of T1 of the 13C nuclei of the ZnTPPS4-TMe-â-CD complex,
MALDI-TOF MS of the TPPS4-TMe-â-CD complex, 1H NMR
spectral changes of TPPS4 upon complexation with â-CD, a
table indicating reliability of the analytical method for deter-
mination of the rate constants, and the analytical data of
TPPOC3PS and its precursors (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
JA020253N
(32) Matsui, Y.; Mochida, K. Bull. Chem. Soc. Jpn. 1979, 52, 2808-2814.
(33) (a) Smithrud, D. B.; Diederich, F. J. Am. Chem. Soc. 1990, 112, 339-343.
(b) Smithrud, D. B.; Wyman, T. B.; Diederich, F. J. Am. Chem. Soc. 1991,
113, 5420-5426. (c) Mordasini Denti, T. Z.; van Gunsteren, W. F.;
Diederich, F. J. Am. Chem. Soc. 1996, 118, 6044-6051.
(30) Jeffrey, G. A.; Saenger, W. Hydrogen Bonding in Biological Structures;
Springer-Verlag: Berlin-Heidelberg, 1991; Chapter 1.
(31) Manka, J. S.; Lawrence, D. S. Tetrahedron Lett. 1989, 7341-7344.
9
9944 J. AM. CHEM. SOC. VOL. 124, NO. 33, 2002