Thermodynamic aspects of the host-guest chemistry of pyrogallol[4]arenes and peralkylated ammonium cations

Article abstract of DOI:10.1016/j.tet.2009.01.066

The stability constants (K), standard free energy (ΔG^o), enthalpy (ΔH^o), and entropy changes (ΔS^o) for the complexation of pyrogallol[4]arenes with ammonium cations of different size and shape have been determined in ethan

Full text of DOI:10.1016/j.tet.2009.01.066

Tetrahedron 65 (2009) 2711–2715
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Thermodynamic aspects of the host–guest chemistry of pyrogallol[4]arenes
and peralkylated ammonium cations
,
,
Bjoern Schnatwinkel a y, Mikhail V. Rekharsky b, Ralf Brodbeck c yy, Victor V. Borovkov b,
Yoshihisa Inoue b , Jochen Mattay
,
a,
*
*
a Organic Chemistry I, Department of Chemistry, Bielefeld University, Bielefeld, Germany
b Department of Applied Chemistry, Osaka University, 2-1 Yamada-oka, Suita 565-0871, Japan
c Theoretical Chemistry, Department of Chemistry, Bielefeld University, Bielefeld, Germany
a r t i c l e i n f o
a b s t r a c t
The stability constants (K), standard free energy (D D D
Go), enthalpy ( Ho), and entropy changes ( So) for the
Article history:
Received 19 September 2008
Received in revised form 6 January 2009
Accepted 7 January 2009
complexation of pyrogallol[4]arenes with ammonium cations of different size and shape have been
determined in ethanol at 298 K by isothermal titration calorimetry. The trends observed in the ther-
modynamic parameters for 1:1 and/or 1:2 host–guest complexation correspond to the systematic
structural changes of the guest molecules. On the basis of the results obtained we compare the com-
plexation properties with two other resorcin[4]arenes and discuss the thermodynamic aspects of this
supramolecular host–guest interactions.
Available online 20 January 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
for rigid container molecules of nanometer-size cavity obtained by
combining calix[4]arenes and pyrogallol[4]arene subunits.6 Sher-
The design of selectively and effectively binding host–guest
systems is an important challenge in modern supramolecular
chemistry. Calix[4]arenes are potent size-selective receptors for
a variety of substrates, in particular, for inorganic and organic cat-
ions.1 During the last two decades, pyrogallol[4]arenesdmembers
of the resorcin[4]arene familydhave attracted broad interest in
supramolecular chemistry and molecular recognition chemistry.
The first successful synthesis of this type of macrocycles according
to the procedure of Ho¨gberg2 was carried out by Tite et al., who
reported in 1989 a new type of the lipophilic macrocyclic host
molecules containing multiple ferrocenyl centers.3 In the early 90s
Dalcanale et al. studied not only the conformation and configura-
tion of these macrocycles by NMR techniques in great detail but
also the preparation, physico-chemical characterization, and me-
somorphic properties of a new class of pyrogallol[4]arene-based
columnar liquid crystals.4 In their pioneering studies, Cram et al.
used pyrogallol[4]arenes as building blocks in the synthesis and
investigation of hemicarcerands.5 Those covalently bonded dimeric
capsules provided the basis for intensive studies of the host–guest
complexation. Reinhoudt et al. introduced the term ‘carceplexes’
man et al. combined the topic of self-assembly with the formation
of carceplex and elucidated the template formation and encapsu-
lation processes in pyrogallol[4]arene-based carceplex by using
highly stable, guest-selective self-assembling structures.7 Rein-
houdt et al. investigated the immobilization of pyrogallol[4]arene-
based carceplexes on a gold surface and the complexation of neutral
and cationic compounds with such a synthetic receptor for the first
time.8 The supramolecular association is driven predominantly
by electrostatic interactions between the guest molecule and the
electron-rich cavity of the macrocyclic host. In the following years
several reports were published on different self-assembled dimeric
pyrogallol[4]arene-based hosts that can encapsulate a wide variety
of inorganic and organic guest compounds in solution and in gas
phase.9 In 1999, Mattay et al. reported that pyrogallol[4]arenes
exist as unique hexameric self-assembled capsules in the solid
state.10 Later, works of the groups of Atwood et al.,11 Rebek and
Shivanyuk,12 and Cohen and Avram13 showed that those hexamers
are stable also in solution. Especially the introduction of diffusion
NMR techniques to this research field by Cohen had a great impact
on the analysis and characterization of the aggregation properties
of resorcin[4]arene and its derivatives. Studies of these aggregates
in the solid state were mainly done by the group of Atwood et al.14
Later Rissanen et al. contributed greatly to the supramolecular
study of these pyrogallol-based macrocycles. For example, they
reported the original method for the synthesis of pyrogallol[6]ar-
enes15 and the complete derivatization of pyrogallol[4]arenes.16
Rissanen et al. further investigated the inclusion phenomena of
* Corresponding authors. Tel.: þ49 521 106 2072; fax: þ49 521 106 6417.
E-mail addresses: ralf.brodbeck1@uni-bielefeld.de (R. Brodbeck), inoue@
chem.eng.osaka-u.ac.jp (Y. Inoue), oc1jm@uni-bielefeld.de (J. Mattay).
y
Tel.: þ49 521 106 2072; fax: þ49 521 106 6417.
yy
Tel.: þ49 521 106 2076; fax: þ49 521 106 6467.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.066

2712
B. Schnatwinkel et al. / Tetrahedron 65 (2009) 2711–2715
R2
N
alkylammonium cations with resorcin[4]arenes and pyrogallol
analogues.17 The complexation of quaternary ammonium ions as
cationic guests resembles to some bioorganic processes based on
R1
R3
cation–p interactions, such as the recognition of the acetylcholine
R4
by acetylcholine-esterase.18,19 The first experimental study in this
context was reported by Schneider et al. in 1988 for the systems
composed of tetraphenolate of resorcin[4]arenes and a series of
quaternary ammonium cations.20 In 2000, Lemaire et al. revealed
that resorcin[4]arenes have a significant affinity to cesium ion
(165 pm in radius) as a guest in solution.9d Two years later Mattay
et al. came to the same conclusion on the basis of the results from
the gas-phase experiments.9f Bearing those results in mind, it is
reasonable to elucidate the influence of larger cations on the
complexation behavior of resorcin[4]arene and its derivatives in
the gas phase. The limited access to inorganic cations larger than
>180 pm and the high toxicity of francium cation were also the
reason why peralkylated ammonium cations were chosen as po-
tential guests for the resorcin[4]arene-based host systems in ad-
dition to their paramount importance in biological processes.
Therefore, Nissinen et al. published the first study on the synthesis
of C-methylated pyrogallol[4]arene and its affinity toward small
quaternary tri- and tetraalkylammonium cations in solid state, in
solution and in gas phase.17c Supplementary to this very detailed
study on the complexation of pyrogallo[4]arenes with ammonium
cations, we now report the results of our thermodynamic study on
the complexation of resorcin[4]arenes 1 and 2 and pyrogallol-
[4]arene 3 (Fig. 1) with a series of tetraalkylammonium cations
4–12 (Fig. 2).
4
R1=R2=R3=R4= CH3
R1=R2=R3=CH3
R1=R2=CH3
R1= CH3
5
6
7
R4=CH2CH3
R3=R4=CH2CH3
R2=R3=R4=CH2CH3
8
9
R1=R2=R3=R4= CH2CH3
R1=R2=CH2CH3
R3=R4=(CH2)2CH3
10 R1= CH2CH3
11 R1=R2=R3=R4= (CH2)2CH3
R2=R3=R4=(CH2)2CH3
12 R1=R2=R3=R4= (CH2)3CH3
Figure 2. Quaternary ammonium cations 4–12 used in this study.
required to obtain reliable results. To perform test reactions it is
strongly recommended to ensure the correct and precise micro-
calorimetric determinations. Nevertheless, the titration microcalo-
rimetry is the most reliable method for determining the
thermodynamic parameters at present time.
2.2. Complexation and aggregation properties
of pyrogallol[4]arenes
As the method of choice for elucidating the thermodynamic
properties of these systems, we chose the isothermal titration
calorimetry (ITC), which enables the direct determination of ther-
modynamic parameters (i.e., complex stability constant (K), stan-
2. Results and discussion
2.1. Determination of thermodynamic quantities
dard free energy (D D D
Go), enthalpy ( Ho), and entropy changes ( So))
A wide variety of experimental methods have been employed for
determining the thermodynamic parameters for the complexation
reactions of calix[4]arenes and resorcin[4]arenes.21 These include
calorimetry,22 electronic absorption,20,23 steady-state fluores-
cence,20,24 nuclear magnetic resonance,20,25 vapor pressure osmo-
sis,26 atomic force microscopy,27 and mass spectrometry.28 These
techniques are frequently employed to determine the equilibrium
constants for resorcin[4]arene complexation. The choice of the
spectrometric method and the experimental procedure depends on
the spectral properties of the used guest and host molecules.
However, calorimetry is the only direct method for determining the
reaction enthalpy. In view of the long history of calorimetry as an
established methodology, it is somewhat surprising that this is not
so widely used in the study of the complexation thermodynamics of
resorcin[4]arene and its derivatives. This is apparently due to
a combination of the need for a relatively large amount of the
sample, sophisticated and delicate equipment, and some expertise
in solution. Further, we can determine the composition of formed
aggregates from the analysis of the binding isotherm.
In the ITC experiment, we observed essentially the same com-
plexation behavior as Nissinen et al. described in their paper.17c
They reported that pyrogallol[4]arenes and the ammonium cations
4 and 7 form dimeric capsules in the crystals formed upon co-
crystallization from methanol. Regarding the complexation prop-
erties of pyrogallol[4]arenes in the gas phase, they observed that
the formation of both monomeric 1:1 and dimeric complexes of the
pyrogallol[4]arene species with 4 and 7 is possible. Furthermore, it
was concluded that in the case of tetramethylammonium cation,
the dimeric aggregate is more abundant than the monomeric 1:1
complex, which is in agreement with our results.9f A similar trend
was observed in the NMR experiments, which revealed that the
formation of dimeric complex is favored for 4, rather than 7. In this
relation, it is to note that pyrogallol[4]arene 3 exclusively forms
dimeric species in ethanol solution because of their ability to form
an unique hydrogen bonding network in the dimer, whilst resor-
cin[4]arenes 1 and 2 do not show such a phenomenon.
X
X
X
H
X
OH
OH HO
HO
OH
HO
HO
OH
2.3. Complex stability and size complementary
In order to elucidate the relationship between the complex
stability constant and the guest size, we first examined the com-
plexation behavior of resorcin[4]arene 1 with the smallest tet-
raalkylated ammonium cation 4 in ethanol to obtain a small K of
350 Mꢀ1, suggesting inherently low affinities of resorcin[4]arenes
to ammonium ions. We suspected that the origin of the low affinity
is the shallow cavity of the resorcin[4]arene and hence introduced
a methyl group on each aromatic ring of the upper rim of 1 to give
H
H
H
R
R
R
R
1
2
3
X = H, R = CH2CH(CH3)2
X = CH3, R = CH2CH(CH3)2
X = OH, R = CH2CH(CH3)2
resorcin[4]arene 2. Indeed, this host gave a larger K of 1100 Mꢀ1
most probably due to the expanded hydrophobic cavity. To further
,
Figure 1. Resorcin[4]arenes 1 and 2, pyrogallol[4]arene 3 as host systems for the
complexation of quaternary ammonium cations.

B. Schnatwinkel et al. / Tetrahedron 65 (2009) 2711–2715
2713
increase the complex stability, we employed pyrogallol[4]arene 3
as a better host for 4 in the next experiment with an expectation
that the extra hydroxyl group at the upper rim enhances the elec-
trostatic interactions in comparison to the less polarized scaffolds 1
and 2. For the stoichiometric 1:1 complex formation, we obtained
the K of 1900 Mꢀ1, which is appreciably larger than that for the
complex 4@2.
decreased population probability compared to 7@3, should hold
true for the shown conformation of 12@3.
2.4. Complexation thermodynamics
As can be seen from the data in Table 1, the complexation of
tetraalkylammonium cations (4–10) with resorcin[4]arenes (1, 2)
and pyrogallol[4]arene (3) is driven primarily by the enthalpic
Interestingly, a second molecule of pyrogallol[4]arene 3 is
bound to 4@3 to form a 1:2 dimeric complex 4@32 with a much
higher K of 14,000 Mꢀ1. The slightly larger guest 5 also forms both
1:1 and 1:2 guest–host complexes. The K1 value for the formation of
5@3 is larger by a factor of 3 than that for 4@3, while the K2 value
for the formation of 5@32 is sixfold smaller than that for 4@32.
Upon further enlargement of the guest size by introducing two
ethyl groups, only the formation of monomeric 1:1 complexes was
observed in ethanol solution with the K of 6900 Mꢀ1 for 6@3 and
7500 Mꢀ1 for 7@3. This result is not consistent with those obtained
in gas phase or solid state, but would be reasonable, since in so-
lution the solvation shell of bound ethanol molecules around the
guest molecule hinders the formation of a dimeric species. By fur-
ther expanding the guest size, the K value starts to decrease to give
2400 Mꢀ1 for 8@3, 1500 Mꢀ1 for 9@3, 850 Mꢀ1 for 10@3, ca. 50 Mꢀ1
for 11@3, and eventually extremely weak interactions with 12,
which is compatible with that observed in gas phase. To support
our conclusions drawn from the thermochemical data and to relate
our conclusions to structural features of the host–guest complexes,
we examined in the framework of Kohn–Sham DFT model
compound with R¼Me (instead of R¼n-Bu) for the three chosen
host–guest complexes 4@3, 7@3, and 12@3. For each of these, we
optimized the structure of one preselected conformer equilibrium
structures and counterpoise corrected (see Details of calculations)
formation energies in the gas phase at T¼0 K were calculated.
Spacefilling representations of the optimized structure are pre-
sented in Figure 3. The counterpoise corrected formation energies
in kJ/mol (the zero point energy-corrected values in the paren-
theses) are ꢀ56.4 (ꢀ48.4), ꢀ40.6 (ꢀ33.0), and ꢀ3.9 for 4@3, 7@3,
and 12@3, respectively. The gradual decrease in the complex for-
mation energy with increasing steric demand of the ammonium
cation is clearly demonstrated. We believe that this trend is caused
by the increasing distance between the pyrogallo[4]arene’s dipole
and the barycentre of the overall positively charged ammonium
cation’s charge cloud, because the ion-dipole interaction should be
the dominating part of the electrostatic interaction between the
guest and the host. Dispersive interactions could be disregarded,
since RIMP2 and BP86 optimized structures are in close agreement
(see Details of calculations). From Figure 3 one can easily deduce
that the chosen conformation of 4@3 should also be important in
solution at room temperature, i.e., when both molecules are rovi-
brating because 4 fits nicely into 3. The shown conformation of 7@3
should be less stable in solution at room temperature compared to
the situation in vacuum at 0 K, because of the increased steric de-
mands of the rovibrating ethyl groups. The same, with an even
gains. However, the enthalpy change (
So) obtained are significantly different between these two types
of hosts. Upon complexation with tetramethylammonium ion (4),
resorcinarenes 1 and 2 give moderate enthalpic gains (ꢀ
Ho) of 14–
16 kJ molꢀ1 with slightly positive entropic gain (T So) of 1–
2 kJ molꢀ1
while pyrogallol[4]arene affords a much larger
enthalpic gain of 47 kJ molꢀ1 and an entropic loss of 28 kJ molꢀ1
The critical difference in the enthalpic gain may be attributed to the
stronger cation– interactions in pyrogallol[4]arene than in resor-
D
Ho) and the entropy change
(D
D
D
,
3
.
p
cin[4]arene. On the other hand, this enthalpic gain is canceled to
some extent by the entropic penalty arising from the more severe
structural freezing in the pyrogallol[4]arene complex.
It is to note that the enthalpic gain upon 1:1 complexation with
pyrogallol[4]arene 3 is comparable for tetramethylethylammonium
(4) and trimethylethylammonium (5) (45–47 kJ molꢀ1), but sud-
denly decreases by introducing another ethyl group to the ammo-
nium ion and reaches a plateau of 31–37 kJ molꢀ1 for bulkier
ammonium ions 6–10, indicating that the introduction of two ethyl
(or bulkier) groups to the guest ammonium critically damages the
cation–p interactions. This observation may be taken as a guideline
for designing best fitting ammonium guests that only one alkyl
group in quaternary ammonium cation can be modified without
damaging the strong cation–
p interactions.
3. Experimental
3.1. General
The host molecules 1–3 are synthesized according to our re-
cently published procedure.29 The one-pot synthesis yields the
most thermodynamically stable C4v-symmetrical bowl-shaped
product, which is stabilized by an intramolecular hydrogen bond-
ing network between the aromatic subunits.
The synthesis of the guest molecules 4–12 was carried out by
the base assisted exhaustive alkylation. All commercially available
starting materials of the best available quality were purchased from
Wako Chemicals and used without further purification.
3.2. Microcalorimetric measurements
An isothermal calorimetry instrument, purchased from Microcal
Inc., Northampton, MA, was used for all microcalorimetric experi-
ments. The ITC instrument was periodically calibrated electrically
using an internal electric heater. The instrument was also calibrated
chemically by measuring the enthalpy of neutralization of HCl with
NaOH and the ionization enthalpy of TRIS buffer. These standard
reactions gave excellent agreement (ꢁ1–2%) with the literature
data.30
Titration microcalorimetry allowed us to determine simulta-
neously the enthalpy value and equilibrium constant from a single
titration curve. Each microcalorimetric titration experiment con-
sisted of 20–40 successive injections: 20 successive injections were
performed when 1:1 complexation (
with 40 successive injections performed when a stepwise 2:1
complexation was expected ( H1, K1,
H2, and K2).30 In both cases,
a constant volume (5 L/injection) of pyrogallol[4]arene solution
DH1 and K1) was expected,
D
D
m
was injected into the reaction cell (1.36 mL) charged with a guest
solution in the same organic solvent; initial concentrations of guest
Figure 3. BP86/TZVP optimized structures of the complexes of pyrogallo[4]arene 3
with the ammonium cations 4 (left), 7 (middle), and 12 (right).

2714
B. Schnatwinkel et al. / Tetrahedron 65 (2009) 2711–2715
Table 1
Complex stability constant (K), standard free energy (D D D
Go), enthalpy ( Ho), and entropy changes (T So) for the complexation of selected quaternary ammonium cationsa with
resorcin[4]arenes and pyrogallol[4]arenes in ethanolic solution at 298.15 K
Complexation reaction
Kb/Mꢀ1
D
Go/kJ molꢀ1
D
Ho/kJ molꢀ1
TD
So/kJ molꢀ1
1þ(CH3)4NþClꢀ (4)¼[1$(CH3)4Nþ]Clꢀ] (4@1)
350ꢁ70
ꢀ14.5ꢁ0.6
ꢀ17.4ꢁ0.2
ꢀ18.7ꢁ0.6
ꢀ23.7ꢁ0.3
ꢀ21.3ꢁ0.6
ꢀ19.0ꢁ0.7
ꢀ21.9ꢁ0.2
ꢀ22.1ꢁ0.1
ꢀ19.3ꢁ0.1
ꢀ18.1ꢁ0.2
ꢀ16.7ꢁ0.3
ꢀ14ꢁ1
0.5ꢁ1
2þ(CH3)4NþClꢀ (4)¼[2$(CH3)4Nþ]Clꢀ (4@2)
1100ꢁ100
ꢀ15.5ꢁ0.3
ꢀ47ꢁ4
1.9ꢁ0.4
3þ(CH3)4NþClꢀ (4)¼[3$(CH3)4Nþ]Clꢀ (4@3)
1900ꢁ400
14,000ꢁ1000 (K2)
5300ꢁ1000
2100ꢁ500 (K2)
6900ꢁ400
7500ꢁ300
2400ꢁ100
1500ꢁ100
850ꢁ100
ꢀ28ꢁ4
ꢀ5ꢁ4
[3$(CH3)4Nþ]Clꢀþ3¼[32$(CH3)4Nþ]Clꢀ (4@32)
ꢀ29ꢁ4
3þ(CH3)3(C2H5)NþClꢀ (5)¼[3$(CH3)3(C2H5)Nþ]Clꢀ (5@3)
[3$(CH3)3(C2H5)Nþ]Clꢀþ3¼[32$(CH3)3(C2H5)Nþ]Clꢀ (5@32)
3þ(CH3)2(C2H5)2NþBrꢀ (6)¼[3$(CH3)2(C2H5)2Nþ]Brꢀ (6@3)
3þ(CH3)(C2H5)3NþClꢀ (7)¼[3$(CH3)(C2H5)3Nþ]Clꢀ (7@3)
3þ(C2H5)4NþClꢀ (8)¼[3$(C2H5)4Nþ]Clꢀ (8@3)
ꢀ45ꢁ4
ꢀ24ꢁ4
ꢀ29ꢁ4
ꢀ48ꢁ4
ꢀ35.3ꢁ0.5
ꢀ35.3ꢁ0.4
ꢀ37.3ꢁ0.4
ꢀ30.7ꢁ0.4
ꢀ34.6ꢁ0.6
zꢀ30 (ꢁ50)
ꢀ13.4ꢁ0.5
ꢀ13.2ꢁ0.4
ꢀ18.0ꢁ0.4
ꢀ12.6ꢁ0.5
ꢀ17.9ꢁ0.7
3þ(C2H5)2(C3H7)2NþBrꢀ (9)¼[3$(C2H5)2(C3H7)2Nþ]Brꢀ (9@3)
3þ(C2H5)(C3H7)3NþBrꢀ (10)¼[3$(C2H5)(C3H7)3Nþ]Br (10@3)
3þ(C3H7)4NþClꢀ (11)¼[3$(C3H7)4Nþ]Clꢀ (11@3)
3þ(C4H9)4NþClꢀ (12)¼[3$(C4H9)4Nþ]Clꢀ (12@3)
z50 (ꢁ150)
c
a
In ITC experiments a solution of the quaternary ammonium salt in ethanol (0.2 mM), placed in the reaction cell of the microcalorimeter, was titrated with a solution of
L each) of the pyrogallol[4]arene solution into the cell.
Stability constant for 1:1 complex, unless noted otherwise; K2 for 1:2 guest–host complexation.
pyrogallo[4]arene (4 mM) in ethanol. Typical ITC experiment consists of 25–50 injections (10
m
b
c
Very low affinity; it cannot be determined under the experimental conditions employed.
and pyrogallol[4]arenes in each run are indicated in Table 1. The
heat of dilution when the pyrogallol[4]arene solution was added to
the blank solution without a guest was determined in each run
using the same number of injections and concentration of pyro-
gallol[4]arene as used in the titration experiments. The dilution
enthalpies determined in these control experiments were sub-
tracted from the enthalpies measured in the titration experiments.
It should be emphasized that the enthalpies of dilution obtained in
all runs were of the same order of magnitude as the enthalpies of
dilution of simple electrolytes such as NaCl at the same
concentration.
The ORIGIN software (Microcal Inc.), which was used to calcu-
late the equilibrium constant and standard molar enthalpy of re-
action from the titration curve in the cases of simple 1:1 and
stepwise 2:1 complexations, gave a standard deviation based on
the scatter of the data points in a single titration curve. The accu-
racy of the calculated thermodynamic quantities for 1:1 complex-
ations was checked by performing several independent titration
runs. The uncertainties in the observed thermodynamic quantities
for 1:1 complexation (Table 1) are two standard deviations of the
mean value unless otherwise stated. Detailed descriptions of each
step of 1:1 and 2:1 complexation processes are given in Table 1.
on the BP86/SVP hypersurfaces (at the stationary points on these hy-
persurfaces), because of the huge number of basis functions. For 12@3
even on the BP86/SVP hypersurface no normal mode analysis could be
achieved due to unsolvable technical problems. All other structures
reported herein (and in the ESI) were confirmed to be true minima by
the normal mode analyses.
Because the calculation of electronic energies for weakly inter-
acting complexes (such as those examined here) within the su-
pramolecular approach (as in this work) is affected by the basis set
superposition error (BSSE)37 we performed counterpoise correc-
tions38 to get BSSE-free formation energies. In the needed single
point calculations we did not use the charge density fitting and
took care of the integration grid points on the ghost atoms. The
reaction energies given in the text are the counterpoise corrected
formation energies (the zero point energy-corrected values are
given in the parentheses).
Cartesian coordinates and electronic energies are available in
Supplementary data.
Acknowledgements
Financial support by the Deutsche Forschungsgemeinschaft (SFB
613) is gratefully acknowledged.
3.3. Details of calculations
Supplementary data
The Kohn–Sham DFT calculations reported herein were performed
with the Gaussian0331 programme, using the BP86 density functional
(containing the B8832 gradient correction for exchange, the VWN-
(III)33 correlation functional and the P8634 gradient correction for
correlation), combined with the TZVP35 basis set (triple zeta quality,
polarization functions on all centers). No significant differences be-
tween the optimized structures of 3 (with R¼H) on the BP86/SVP and
RIMP2/SVP hypersurfaces were found, indicating an acceptable accu-
racy of the chosen density functional.
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2009.01.066.
References and notes
1. Bo¨hmer, V. Angew. Chem., Int. Ed. Engl. 1995, 34, 713–745.
2. Ho¨gberg, A. G. S. J. Org. Chem. 1980, 45, 4498–4500.
3. Beer, P. D.; Smythe, A. C.; Tite, E. L.; Ibbotson, A. J. Organomet. Chem. 1989, 376,
C11–C14.
In the structure optimization (normal mode analyses) a pruned
integration grid of 99 (75) radial shells with 590 (302) angular
points per shell for all atoms was used. The threshold for maximum
force (maximum displacement in internal coordinates) was
4.5ꢂ10ꢀ4 a.u. (1.8ꢂ10ꢀ3 a.u.), resulting in equilibrium structures
with energies consistent to 10ꢀ7 a.u., the same accuracy as for the
electronic energy. In the structure optimization and in the normal
mode analyses the charge density fitting approximation for Cou-
lomb integrals36 with automatically generated auxiliary basis sets
was used.
4. (a) Cometti, G.; Dalcanale, E.; DuVosel, A.; Levelut, A. M. Chem. Commun. 1990,
163–165; (b) Bonsignore, S.; Dalcanale, E.; Cometti, G.; DuVosel, A. Liq. Cryst.
1990, 8, 639–649; (c) Abis, L.; Arrighi, V.; Cometti, G.; Dalcanale, E.; DuVosel, A.
Liq. Cryst. 1991, 9, 277–284; (d) Dalcanale, E.; DuVosel, A.; Levelut, A. M.;
Malthete. Liq. Cryst. 1991, 10, 185–198; (e) Bonsignore, S.; DuVosel, A.; Gu-
glielmetti, G.; Dalcanale, E.; Ugozzoli, F. Liq. Cryst. 1993, 13, 471–482; (f) Ricco,
M.; Dalcanale, E. J. Phys. Chem. 1994, 98, 9002–9008; (g) Lippmann, T.; Dalca-
nale, E.; Mann, G. Gazz. Chim. Ital. 1995, 125, 595–599.
5. (a) Cram, D. J.; Jaeger, R.; Deshayes, K. J. Am. Chem. Soc. 1993, 115, 10111–10116;
(b) Robbins, T. A.; Knobler, C. B.; Bellew, D. R.; Cram, D. J. J. Am. Chem. Soc. 1994,
116, 111–120; (c) Yoon, J.; Sheu, C.; Houk, K. N.; Knobler, C. B.; Cram, D. J. J. Org.
Chem. 1996, 61, 9323–9339; (d) Helgeson, R. C.; Paek, K.; Knobler, C. B.; Mav-
erick, E. F.; Cram, D. J. J. Am. Chem. Soc. 1996, 118, 5590–5604; (e) Helgeson, R. C.;
Knobler, C. B.; Cram, D. J. J. Am. Chem. Soc. 1997, 119, 3229–3244; (f) Yoon, J.;
Cram, D. J. Chem. Commun. 1997, 497–498.
For 3, 4, 7, and 12 the normal mode analysis was performed on the
BP86/TZVP hypersurfaces, but those for 4@3 and 7@3 were performed

B. Schnatwinkel et al. / Tetrahedron 65 (2009) 2711–2715
2715
6. (a) Timmerman, P.; Verboom, W.; van Veggel, F. C. J. M.; van Duynhoven, J. P.;
Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl. 1994, 33, 1292–1295; (b) Tim-
merman, P.; van Veggel, F. C. J. M.; van Duynhoven, J. P.; Reinhoudt, D. N. Angew.
Chem., Int. Ed. Engl. 1994, 33, 2345–2348; (c) Timmerman, P.; Nierop, K. G. A.;
Brinks, E. A.; Verboom, W.; van Veggel, F. C. J. M.; van Hoorn, W. P.; Reinhoudt,
D. N. Chem.dEur. J. 1995, 1, 132–143; (d) van Wageningen, A. M. A.; Timmer-
man, P.; van Duynhoven, J. P.; Verboom, W.; van Veggel, F. C. J. M.; Reinhoudt,
D. N. Chem.dEur. J. 1997, 3, 639–654; (e) Higler, I.; Verboom, W.; van Veggel, F.
C. J. M.; De Jong, F.; Reinhoudt, D. N. Liebigs Ann. Recl. 1997, 1577–1586.
7. (a) Chapman, R. G.; Sherman, J. C. J. Am. Chem. Soc. 1995, 117, 9081–9082; (b)
Nakamura, K.; Sheu, C.; Keating, A. E.; Houk, K. N.; Sherman, J. C. J. Am. Chem.
Soc. 1997, 119, 4321–4322; (c) Chapman, R. G.; Sherman, J. C. J. Am. Chem. Soc.
1998, 120, 9818–9826.
8. (a) Huisman, B.; Rudkevich, D. M.; van Veggel, F. C. J. M.; Reinhoudt, D. N.
J. Am. Chem. Soc. 1996, 118, 3523–3524; (b) Huisman, B.; van Veggel, F. C. J. M.;
Reinhoudt, D. N. Pure Appl. Chem. 1998, 70, 1985–1992; (c) Higler, I.; Tim-
merman, P.; Verboom, W.; Reinhoudt, D. N. J. Org. Chem. 1996, 61, 5920–5931;
(d) Friggeri, A.; van Veggel, F. C. J. M.; Reinhoudt, D. N.; Kooyman, R. P. H.
Langmuir 1998, 14, 5457–5463; (e) Boerrigter, H.; Lugtenberg, R. J. W.;
Egberink, R. J. M.; Verboom, W.; Reinhoudt, D. N.; Spek, A. L. Gazz. Chim. Ital.
1998, 127, 709–716; (f) Boerrigter, H.; Tomasberger, T.; Verboom, W.;
Reinhoudt, D. N. Eur. J. Org. Chem. 1999, 665–674; (g) Huisman, B.; Rudkevich,
D. M.; Farran, A.; Verboom, W.; van Veggel, F. C. J. M.; Reinhoudt, D. N. Eur. J.
Org. Chem. 2000, 269–274.
9. (a) Luetzen, A.; Renslo, A. R.; Schalley, C. A.; O’Leary, B. M.; Rebek, J., Jr. J. Am. Chem.
Soc.1999,121, 7455–7456; (b) Chapman, R. G.; Sherman, J. C. J. Org. Chem. 2000, 65,
513–516; (c) Friggeri, A.; van Veggel, F. C. J. M.; Reinhoudt, D. N. Chem.dEur. J.1999,
5, 3595–3602; (d) Chitry, F.; Pellet-Rostaing, S.; Nicod, L.; Gass, J.; Foos, J.; Guy, A.;
Lemaire, M. J. Phys. Chem. A 2000, 104, 4121–4128; (e) Piatnitski, E. L.; Flowers, R.
A.; Deshayes, K. Chem.dEur. J. 2000, 6, 999–1006; (f) Letzel, M. C.; Agena, C.;
Mattay, J. J. Mass Spectrom. 2002, 37, 63–68; (g) Beyeh, N. K.; Kogej, M.; Ahman, A.;
Rissanen, K.; Schalley, C. A. Angew. Chem., Int. Ed. 2006, 45, 5214–5218.
10. Gerkensmeier, T.; Iwanek, W.; Agena, C.; Fro¨hlich, R.; Kotila, S.; Na¨ther, C.;
Mattay, J. Eur. J. Org. Chem. 1999, 2257–2262.
17. (a) Mansikkama¨ki, H.; Nissinen, M.; Rissanen, K. Cryst. Eng. Commun. 2005, 7,
519–526; (b) Mansikkama¨ki, H.; Schalley, C. A.; Nissinen, M.; Rissanen, K. New J.
Chem. 2005, 29, 116–127; (c) Ahman, A.; Luostarinen, M.; Rissanen, K.; Nissinen,
M. New J. Chem. 2007, 31, 169–177.
18. For a review, see: Ma, J. C.; Dougherty, D. A. Chem. Rev. 1997, 97, 1303–1324.
19. Casnati, A.; Sciotto, D.; Arena, G. In Calixarenes; Asfari, Z., Bo¨hmer, V., Har-
rowfield, V., Vicens, J., Eds.; Kluwer Academic: Dordrecht, Netherland, 2001,
Chapter 24, and references therein.
20. Schneider, H.-J.; Gattes, D.; Schneider, U. J. Am. Chem. Soc. 1988, 110, 6449–6454.
21. For a review, see: Ludwig, R. Microchim. Acta 2005, 152, 1–19.
22. Danil de Namor, A. F.; Cleverley, R. M.; Zapata-Ormachchea, M. L. Chem. Rev.
1998, 98, 2495–2525.
23. Saha, A.; Nayak, S. K.; Chattopadhyay, S.; Mukherjee, A. K. J. Phys. Chem. A 2004,
108, 8223–8228.
24. Sarmentero, M. A.; Ballester, P. Org. Biomol. Chem. 2007, 5, 3046–3054.
25. Ballester, P.; Shivanyuk, A.; Far, A. F.; Rebek, J., Jr. J. Am. Chem. Soc. 2002, 124,
14014–14016.
26. Higler, I.; Grave, L.; Breuning, E.; Verboom, W.; de Jong, F.; Fyles, T. M.; Rein-
houdt, D. N. Eur. J. Org. Chem. 2000, 1727–1734.
27. Eckel, R.; Ros, R.; Decker, B.; Mattay, J.; Anselmetti, D. Angew. Chem., Int. Ed.
2005, 44, 484–488.
28. Tafi, A.; Botta, B.; Delle Monache, G.; Fillipi, A.; Speranza, M. Chem.dEur. J.
2004, 10, 4126–4135.
29. Schnatwinkel, B.; Stoll, I.; Mix, A.; Rekharsky, M. V.; Borovkov, V. V.; Inoue, Y.;
Mattay, J. Chem. Commun. 2008, 3873–3875.
30. Rekharsky, M. V.; Inoue, Y. J. Am. Chem. Soc. 2000, 122, 4418–4435.
31. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.;
Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J.
V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.;
Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.;
Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian03,
Revision C.02; Gaussian: Wallingford, CT, 2004.
32. Becke, A. D. Phys. Rev. A: Gen. Phys. 1988, 38, 3098–3100.
33. Vosko, S. H.; Wilk, L.; Nusair, N. Can. J. Phys. 1980, 58, 1200–1211.
34. Perdew, J. P. Phys. Rev. B: Condens. Matter 1986, 33, 8822–8824.
35. Scha¨fer, A.; Huber, C.; Ahlrichs, R. J. Chem. Phys. 1994, 100, 5829–5835.
36. (a) Dunlap, B. I. J. Chem. Phys. 1983, 78, 3140–3142; (b) Dunlap, B. I. J. Mol. Struct.
(THEOCHEM) 2000, 529, 37–40.
37. van Duijneveldt, F. B.; van Duijneveldt-van de Rijdt, J. G. C. M.; Nielsen, I. M. B.;
van Lenthe, J. H. Chem. Rev. 1994, 94, 1873–1885.
38. Boys, S. F.; Bernardi, F. Mol. Phys. 1970, 19, 553–566.
11. Atwood, J. L.; Barbour, J. L.; Jerga, A. Chem. Commun. 2001, 2376–2377.
12. Shivanyuk, A.; Rebek, J., Jr. Chem. Commun. 2001, 2374–2375.
13. Avram, L.; Cohen, Y. Org. Lett. 2003, 5, 3329–3332.
14. (a) McKinlay, R. M.; Thallapally, P. K.; Atwood, J. L. Chem. Commun. 2006, 2956–
2958; (b) Heaven, M. W.; Cave, G. W. V.; McKinlay, R. M.; Antesberger, J.;
Dalgarno, S. J.; Thallapally, P. K.; Atwood, J. L. Angew. Chem., Int. Ed. 2006, 45,
6221–6224; (c) Dalgarno, S. J.; Bassil, D. B.; Tucker, S. A.; Atwood, J. L. Angew.
Chem., Int. Ed. 2006, 45, 7019–7022; (d) Power, N. P.; Dalgarno, S. J.; Atwood, J. L.
New J. Chem. 2007, 31, 17–20; (e) Dalgarno, S. J.; Power, N. P.; Atwood, J. L. Chem.
Commun. 2007, 3447–3449; (f) Dalgarno, S. J.; Antesberger, J.; McKinlay, R. M.;
Atwood, J. L. Chem.dEur. J. 2007, 13, 8248–8255; (g) Power, N. P.; Dalgarno, S. J.;
Atwood, J. L. Angew. Chem., Int. Ed. 2007, 46, 8601–8604; (h) Dalgarno, S. J.;
Power, N. P.; Warren, J. E.; Atwood, J. L. Chem. Commun. 2008, 1539–1541.
15. Ahman, A.; Nissinen, M.; Rissanen, K. Supramol. Chem. 2004, 16, 505–512.
16. Ahman, A.; Luostarinen, M.; Schalley, C. A.; Nissinen, M.; Rissanen, K. Eur. J. Org.
Chem. 2005, 2793–2801.