Host-guest complexation behavior of resorcinarenes with tetraalkylammonium ions and N-methylpyridinium ions in methanol: The effect of bulky hydrophobic substituents at the extra-annular positions

Article abstract of DOI:10.1080/10426500600865152

The host-guest interaction of C-methylresorcin[4]arene and its derivative having four tert-butylsulfanylmethyl groups at the extra-annular positions was studied by ¹H NMR spectroscopy in CD₃OD. Based on the association constants (Ka) and the complexation-induced NMR shifts (CIS), it was concluded that the bulky substituents create a deep cavity with a narrow entrance and improve the size and shape selectivity. Copyright Taylor & Francis Group, LLC.

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Host–Guest Complexation
Behavior of Resorcinarenes
with Tetraalkylammonium Ions
and N-Methylpyridinium Ions in
Methanol: The Effect of Bulky
Hydrophobic Substituents at
the Extra-Annular Positions
Osamu Morikawa a , Hiroshi Yamaguchi a , Yoshiko
Katsube a , Kazuyuki Abe a , Kazuhiro Kobayashi a
Hisatoshi Konishi a
a Department of Materials Science, Tottori
University, Tottori, Japan
&
Version of record first published: 22 Nov 2006.
To cite this article: Osamu Morikawa , Hiroshi Yamaguchi , Yoshiko Katsube , Kazuyuki
Abe , Kazuhiro Kobayashi & Hisatoshi Konishi (2006): Host–Guest Complexation
Behavior of Resorcinarenes with Tetraalkylammonium Ions and N-Methylpyridinium
Ions in Methanol: The Effect of Bulky Hydrophobic Substituents at the Extra-
Annular Positions, Phosphorus, Sulfur, and Silicon and the Related Elements, 181:12,
2877-2886
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Phosphorus, Sulfur, and Silicon, 181:2877–2886, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600865152
Host–Guest Complexation Behavior of Resorcinarenes
with Tetraalkylammonium Ions and N-Methylpyridinium
Ions in Methanol: The Effect of Bulky Hydrophobic
Substituents at the Extra-Annular Positions
Osamu Morikawa
Hiroshi Yamaguchi
Yoshiko Katsube
Kazuyuki Abe
Kazuhiro Kobayashi
Hisatoshi Konishi
Department of Materials Science, Tottori University, Tottori, Japan
The host–guest interaction of C-methylresorcin[4]arene and its derivative having
four tert-butylsulfanylmethyl groups at the extra-annular positions was studied
1
by H NMR spectroscopy in CD OD. Based on the association constants (Ka) and
3
the complexation-induced NMR shifts (CIS), it was concluded that the bulky sub-
stituents create a deep cavity with a narrow entrance and improve the size and
shape selectivity.
Keywords Hydrophobic interaction; molecular recognition; N-methylpyridinium ions;
quaternary ammonium ions; resorcinarene
INTRODUCTION
The construction of host molecules with high affinity and selectivity is
one of the major goals of supramolecular chemistry.1 Calixarenes and
resorcinarenes are readily available synthetic macrocyclic compounds
and have been widely used as host molecules.2,3 In order to improve
their complexation properties, a variety of functionalizations has been
developed.4 Thus, the introduction of functional groups at the periph-
eral positions of the macrocycles has resulted in the enhancement of
the internal surface area of the cavity, leading to the improved affinity
Received July 28, 2005; accepted May 4, 2006.
Address correspondence to Hisatoshi Konishi, Tottori University, Department of
Materials Science, Faculty of Engineering, 4-101 Koyama-minami, Tottori, 680-8552
Japan. E-mail: konis@chem.tottori-u.ac.jp
2877

2878
O. Morikawa et al.
FIGURE 1 Host compounds and their space-filling model representation.
and/or selectivity derived from the interaction between the host and
guest molecules.5,6
The resorcin[4]arenes consist of four resorcinols, which form an
electron-rich cavity able to include specific guest molecules such as am-
monium ions and sugars by cation-π7,8 and CH-π9−11 interactions. The
characteristic feature of the resorcin[4]arenes is the presence of strong
electron-donating OH groups, which increase the electron density of
the resorcinol rings. From this point of view, we have been interested
in the resorcin[4]arene derivatives bearing the OH groups.12−14 We
previously reported that the reaction of C-methylresorcin[4]arene (1)
with 2-methyl-2-propanethiol and formaldehyde in acetic acid yields
the resorcin[4]arene (2), which has eight OH groups and four tert-
butylsulfanylmethyl substituents.15,16 As shown in Figure 1, this com-
pound has a deep cavity of about a 0.8-nm depth, if the substituents
align vertically at the peripheral positions. On the other hand, the re-
sorcinarene 1 has a cavity with a depth of less than 0.4 nm. To obtain
insight into the effect of the bulky hydrophobic substituents on the com-
plexation behavior, we have investigated the inclusion phenomena of 1
and 2 with tetraalkylammonium ions and pyridinium ions in methanol
by 1H NMR spectroscopy. These cations have been widely used as guest
molecules for complexation with calixarenes and resorcinarenes.8,17−19

Host–Guest Complexation Behavior
2879
FIGURE 2 Guest compounds.
RESULTS AND DISCUSSION
The complexation behavior of hosts 1 and 2 with guests in CD3OD
was investigated by an 1H NMR titration experiment (Job’s plot).
The studied guests (Figure 2) include Tetramethylammonium Bromide
(TMA), Tetraethylammonium Bromide (TEA), N-Methylpyridinium
Iodide (Py), and 4-Tert-Butyl-N-Methylpyridinium Iodide (TBPy). The
general features of the NMR study are as follows. First, in all cases, ex-
cept for the combination of 2 and TEA, large upfield shifts of the guest
signals were observed in their NMR spectra. In addition, the upfield
shift values, ꢀδ = δ(free guest)-δ(complexed guest), increase upon in-
creasing the host/guest ratio. These data are consistent with the view
that a guest is incorporated into the aromatic cavity of the host and
subjected to the ring current effect of the aromatic rings. Second, no dis-
tinct signals ascribed to the free guest, and the host–guest species could
be observed, thus indicating that the host–guest complexation equilib-
rium has a very fast exchange rate compared to the NMR time scale.
The association constants (Ka) of the complexes and the complexation-
induced NMR shifts (CIS) of the guest molecules are summarized in
Table I.
Complexation with Tetraalkylammonium Ions
TMA is a small spherical guest molecule. The Job’s plot for the com-
plexation of host 1 and TMA is shown in Figure 3. The complicated data
suggested the presence of a competitive complex formation with distinct
stoichiometries. Indeed, it is well known that simple resorcinarenes
such as 1 form 1:120,21 and 2:122,23 host–guest inclusion complexes with
small quaternary ammonium ions in solid state. The 2:1 type complexes
have a capsular structure in which a quaternary ammonium ion was
encapsulated between the cavities of the two resorcinarene molecules.

2880
O. Morikawa et al.
TABLE I Complexation-Induced Shift (CIS) and Association
Constants (Ka) Derived From NMR Titrations With Host 1 and 2
Measurements in CD3OD at 303 K
Host 1
2:1 Complex
CIS Ka
Host 2
1:1 Complex
CIS Ka
1:1 Complex
Guest Compounds
Proton CIS
Ka
CH3 1.32 3.1 × 10
2.39 3.6 × 102
1.45 2.7 × 102
CH3 0.95
7.0 × 10
NDa
CH2 1.21
γ -H 2.65
β-H 2.66
1.5 × 102
4.85
4.51
3.36
3.24
6.5 × 10
3.3 × 102
α-H 2.42
N-CH3 1.67
4.82
2.42
3.70
2.44
C-CH3 0.35
β-H 1.27
1.7 × 102
0.15
0.82
4.8 × 102
α-H 2.40
N-CH3 2.47
2.39
3.07
aNot determined. See text.
The capsule structure was also stabilized by polar solvent molecules
with a multiple hydrogen-bonding network. Therefore, it can be pre-
sumed that both types of complexes are present in the solution. The
computational analysis of the relationship between the initial concen-
trations of 1 and TMA and the chemical shift change of TMA gave the
values of Ka1 = 31 M−1 and CIS (CH3) = 1.32 ppm for the 1:1 complex
and Ka2 = 360 M−1 and CIS (CH3) = 2.39 ppm for the 2:1 complex.

Host–Guest Complexation Behavior
2881
FIGURE 3 A Job’s plot for the complexation of 1 and TMA. Total concentra-
tion: [1]0 + [TMA]0 = 4.0 × 10−3 mol/L.
In contrast, for host 2 with TMA, a 1:1 type complex formation
was evidenced by the Job’s plot. Thus, the values of Ka = 270 M−1 and
CIS(CH3) = 1.45 ppm are obtained using a nonlinear least-square cal-
culation. The observed difference in 1 and 2 for TMA is ascribed to
the hydrophobic bulky substituents at the peripheral position of the
cavity, which prevent the interaction between the two resorcinarene
molecules; then the formation of a 2:1 complex is unfavorable.
Next, we examined TEA as a guest molecule, which is spherical and
larger than TMA. When resorcinarene 1 was used as the host molecule,
the Job’s plot suggested that a 1:1 complex is the predominant species.
On the other hand, resorcinarene 2 produced only slight upfield shifts
of the TEA signals. Therefore, the precise parameters for the complex-
ation could not be calculated using our method, and it is presumed that
the value of Ka is very small. This phenomenon is ascribed to the bulky
tert-butyl groups, which narrow the entrance of the cavity to exclude
the inclusion of a large TEA molecule.
Complexation with Pyridinium Ions
Py has an ellipsoidal structure and interacts with the aromatic cavity
via N-CH3-π and pyridinium CH-π interactions. The Job’s plot for the
complexation behavior of host 1 and Py conflicts with the formation of
a single species. Thus the complexation parameters were calculated by

2882
O. Morikawa et al.
assuming the formation of 1:1 and 2:1 complexes, which are shown in
Table I. The upfield shifts for all protons indicate that both the pyri-
dinium moiety and the N-methyl group were randomly included in the
cavity, although the comparison of the CIS values suggests that the
cavity of 1 somewhat prefers to interact via the pyridinium CH-π. On
the other hand, the Job’s plot for the host 2-Py complex is consistent
with a 1:1 host–guest complexation. The magnitude of the CIS of Py
is in the order of α-H > γ -H > β-H > N-CH3. Again, this trend indicates
that the pyridinium moiety is slightly preferred over the N-CH3 group
in the cavity of host 2.
The guest molecule TBPy has a tert-butyl group at the γ -position.
The size of the tert-butyl group is comparable to that of TMA, and then
TBPy may enter into the cavity not from only the N-CH3 end, but also
the tert-butyl end.
For both host compounds, the Job’s plots for the complexation with
TBPy clearly indicated the formation of the 1:1 type complexes. The
Job’s plot for host 2-TBPy is shown in Figure 4. In the case of host 1,
the difference in the CIS values between the N-CH3 protons and the
C-CH3 protons is 2.12 ppm. On the other hand, in the case of host 2, the
difference is 2.92 ppm. From a comparison of these values, it can be es-
timated that host 2 significantly controls the alignment of the included
TBPy molecule in the cavity. This is because the tert-butyl substitution
FIGURE 4 A Job’s plot for the complexation of 2 and TBPy. Total concentra-
tion: [2]0 + [TBPy]0 = 3.0 × 10−3 mol/L.

Host–Guest Complexation Behavior
2883
FIGURE 5 Schematic representation for the complex of resorcinarene 2 and
TBPy. The aromatic rings are shown by the dark C C bonds.
at the γ -position sterically prevents the pyridinium CH-π interaction
with the aromatic cavity. The Ka value for the complex of 2 with TBPy
was 480 M−1, which is 2.8-fold greater than that of 1. This enhancement
in the Ka value is attributed to the hydrophobic interaction between the
tert-butyl groups in both the host and guest molecules. The computer-
generated structure for the complex of resorcinarene 2 and TBPy is
shown in Figure 5.
CONCLUSION
The host–guest complexation behavior of resorcinarenes 1 and 2 with
tetraalkylammonium ions and N-methylpyridinium ions was investi-
1
gated by H NMR spectroscopy in CD3OD. The resorcinarene 2 hav-
ing four tert-butylsulfanylmethyl groups at the extra-annular positions
showed a superior size and shape selectivity than the resorcinarene
1. It is concluded that the four bulky hydrophobic substituents at the
peripheral positions create a deep hydrophobic cavity with a narrow
entrance in methanol.

2884
O. Morikawa et al.
EXPERIMENTAL
Materials
Resorcinarene 1 was synthesized from resorcinol and acetaldehyde
using a literature procedure.24 Resorcinarene 2 was prepared by the
thiomethylation of 1 in acetic acid as previously reported.16 Py and
TBPy were prepared by methylation of the corresponding pyridines
with iodomethane in ethanol at an ambient temperature for 24 h in the
dark.
1H NMR Spectroscopy
1H NMR spectra were recorded using a 270 MHz JEOL GX270 spec-
trometer at 30◦C. CD3OD (99.8% isotopic purity, Merck) was used as
the solvent, and the residual signal of the nondeuterated fraction of its
methyl group was taken as the internal reference, δ = 3.30.
Determination of Parameters
The stoichiometries of the inclusion complexes were determined us-
ing the continuous variation method (Job’s method).25 This method in-
1
volves running a series of H NMR experiments that varies the host-
to-guest ratios, while the total molar concentration of the host and
guest ([H]0 + [G]0) remains constant. The parameters are calculated
as follows. First, the upfield shifts (ꢀδ) of the appropriate signals of
the guest molecule were observed. Second, the ꢀδ · [G]0 values were
plotted versus the molar fraction of the guest ([G]0/{[G]0 + [H]0}) to
produce the Job’s curve. The stoichiometry of the complex is obtained
from the x-coordinate at the maximum in this curve. Third, the asso-
ciation constants (Ka) of the complexes and the complexation-induced
NMR shifts (CIS) of the guest molecules were simultaneously obtained
by a computer-assisted nonlinear least-square analysis.26
The parameters for the complexation 1-TMA and 1-Py were ana-
lyzed as follows. The association constants Ka1 (1:1 complex; HG) and
Ka2 (2:1 complex; H2G) are expressed by the following equations.
Ka1 = [HG]/(([H]0 − [HG] − 2[H2G])([G]0 − [HG] − [H2G])) (1)
Ka2 = [H2G]/(([H]0 − [HG] − 2[H2G])[HG])
(2)
Eqs.(1) and (2) can be analytically solved and provide the values for
[HG] and [H2G] at the given values of Ka1, Ka2, [H]0, and [G]0. The

Host–Guest Complexation Behavior
2885
observed ꢀδ value is expressed by Eq. (3), where CIS1 and CIS2 are the
CIS values for the 1:1 and 2:1 complexes, respectively.
ꢀδ = CIS1([HG]/[G]0) + CIS2([H2G]/[G]0)
(3)
By using several sets of experimental data ([H]0, [G]0, ꢀδ), together
with the estimated values of Ka1 and Ka2, the CIS1 and CIS2 parame-
ters can be calculated using the least-square method. Finally, the sum
of the square of the difference between the calculated and observed
chemical shift change is minimized by the systematic variation of Ka1
and Ka2.
REFERENCES
[1] J.-M. Lehn, Supramolecular Chemistry: Concepts and Perspectives (VCH,
Wheinheim, 1995).
[2] V. Bo¨hmer, Angew. Chem., Int. Ed. Engl., 34, 713 (1995).
[3] P. Timmerman, W. Verboom, and D. N. Reinhoudt, Tetrahedron, 52, 2663 (1996).
[4] Z. Asfari, V. Bo¨hmer, J. Harrowfield, and J. Vicens (Eds.), Calixarenes 2001 (Kluwer,
Dordrecht, 2001).
[5] D. J. Cram and J. M. Cram, Container Molecules and Their Guests, Monographs in
Supramolecular Chemistry (The Royal Society of Chemistry, Cambridge, 1994).
[6] D. M. Rudkevich and J. Rebek, Jr., In G. J. Lumetta, R. D. Rogers, and A. S.
Gopalan (Eds.), Calixarenes for Separations, pp. 270–282 (American Chemical
Society, Washington, DC, 2000).
[7] J. C. Ma and D. A. Dougherty, Chem. Rev., 97, 1303 (1997).
[8] H.-J. Schneider, D. Guttes, and U. Schneider, J. Am. Chem. Soc., 110, 6449 (1988).
[9] K. Kobayashi, Y. Asakawa, Y. Kato, and Y. Aoyama, J. Am. Chem. Soc., 114, 10307
(1992).
[10] T. Fujimoto, R. Yanagihara, K. Kobayashi, and Y. Aoyama, Bull. Chem. Soc. Jpn.,
68, 2113 (1995).
[11] M. Nishio, M. Hirota, and Y. Umezawa, The CH/p Interaction (Wiley-VCH, New
York, 1998).
[12] H. Konishi, T. Tamura, H. Ohkubo, K. Kobayashi, and O. Morikawa, Chem. Lett.,
685 (1996).
[13] O. Morikawa, K. Nakanishi, M. Miyashiro, K. Kobayashi, and H. Konishi,
Synthesis, 233 (2000).
[14] H. Konishi, O. Morikawa, K. Kobayashi, K. Abe, and A. Ohkubo, Tetrahedron Lett.,
44, 7425 (2003).
[15] H. Konishi, H. Yamaguchi, M. Miyashiro, K. Kobayashi, and O. Morikawa,
Tetrahedron Lett., 37, 8547 (1996).
[16] O. Morikawa, M. Miyashiro, H. Yamaguchi, K. Kobayashi, and H. Konishi,
Supramolecular Chemistry, 11, 67 (1999).
[17] A. Arduini, A. Pochini, and A. Secchi, Eur. J. Org. Chem., 2325 (2000).
[18] K. Araki, T. Watanabe, M. Oda, H. Hayashida, M. Yasutake, and T. Shinmyouzu,
Tetrahedron Lett., 42, 7465 (2001).
[19] K. Araki, K. Hisaichi, T. Kanai, and S. Shinkai, Chem. Lett., 569 (1995).
[20] K. Murayama and K. Aoki, Chem. Commun., 119 (1997).

2886
O. Morikawa et al.
[21] M. Ma¨kinen, P. Vainiotalo, M. Nissinenn, and K. Rissanen, J. Am. Soc. Mass
Spectrom., 14, 143 (2003).
[22] M. Mansikkama¨ki, M. Nissinenn, C. A. Schalley, and K. Rissanen, New J. Chem.,
27, 88 (2003).
[23] M. Mansikkama¨ki, M. Nissinenn, and K. Rissanen, Chem. Comm., 1902 (2002).
[24] A. G. S. Ho¨gberg, J. Org. Chem., 45, 4498 (1980).
[25] C. Y. Huang, Methods in Enzymology, 87, 509 (1982).
[26] K. Hirose, J. Incl. Phenom. Macrocycl. Chem., 39, 193 (2001).