Substituent effects on axle binding in amide pseudorotaxanes: Comparison of NMR titration and ITC data with DFT calculations

Article abstract of DOI:10.1039/c2ob25196e

The binding behaviour of differently substituted diamide axle molecules to Hunter/Voegtle tetralactam macrocycles was studied with a combination of NMR titration, isothermal titration calorimetry (ITC) experiments and calculations employing density functi

Full text of DOI:10.1039/c2ob25196e

View Online / Journal Homepage / Table of Contents for this issue
Organic &
Biomolecular
Chemistry
This article is part of the
OBC 10th anniversary
themed issue
All articles in this issue will be gathered together
online at
www.rsc.org/OBC10

Dynamic Article Links
Organic &
View Online
Biomolecular
Chemistry
Cite this: Org. Biomol. Chem., 2012, 10, 5954
www.rsc.org/obc
PAPER
Substituent effects on axle binding in amide pseudorotaxanes: comparison of
NMR titration and ITC data with DFT calculations†‡
Lena Kaufmann,a Egor V. Dzyuba,a Friedrich Malberg,b Nora L. Löw,a Matthias Groschke,a
Boris Brusilowskij,a Juhani Huuskonen,c Kari Rissanen,c Barbara Kirchner*b and Christoph A. Schalley*a
Received 26th January 2012, Accepted 23rd March 2012
DOI: 10.1039/c2ob25196e
The binding behaviour of differently substituted diamide axle molecules to Hunter/Vögtle tetralactam
macrocycles was studied with a combination of NMR titration, isothermal titration calorimetry (ITC)
experiments and calculations employing density functional theory (DFT), along with dispersion-corrected
exchange-correlation functionals. Guests with alkyl or alkenyl chains attached to the diamide carbonyl
groups have a significantly higher binding affinity to the macrocycle than guests with benzoyl amides and
their substituted analogues. While the binding of the benzoyl and alkenyl substituted axles is
enthalpically driven, the alkyl-substituted guest binds mainly because of a positive binding entropy. The
electronic effects of para-substituents at the benzoyl moieties have an influence on the binding affinities.
Electron donating substituents increase, while electron-withdrawing substituents decrease the binding
energies. The binding affinities obtained from both NMR titration and ITC experiments correlate well
with each other. The substituent effects observed in the experimental data are reflected in adiabatic
interaction energies calculated with density functional methods. The calculated structures also agree well
with pseudorotaxane crystal structures.
interlocked supramolecular architectures have been synthesized8
Introduction
and were analyzed with respect to multivalent binding.9 Other,
Pseudorotaxanes are weakly bound host–guest complexes
bearing a thread-like linear axle that penetrates the cavity of a
macrocyclic host.1 They are the precursors of their mechanically
interlocked siblings, i.e. rotaxanes and catenanes, and therefore
play a pivotal role in the construction of molecular machines
based on interlocked molecules.2 Understanding the binding
properties of pseudorotaxanes has thus an important impact on
the development of template effects for rotaxane and catenane
synthesis which can be, for example, based on metal complexa-
tion,3 charge transfer interactions,4 or hydrogen bonding to neutral
amides,5 secondary ammonium ions,6 or anions.7 Multiply
squaraine-based, fluorescent rotaxanes have been used as long-
term stable dyes in biological research.10
Tetralactam macrocycles (TLM) of the Hunter/Vögtle-type are
well-known as host molecules and as rotaxane or catenane
wheels. They bear four converging amide groups, which can
form hydrogen bonds to suitable axle molecules. This property
has not only been utilized for rotaxane and catenane synthesis,
but also for the construction of quartz microbalance sensors that
can detect carbonyl compounds11 and for STM investigations of
pseudorotaxane formation in TLM monolayers on gold sur-
faces.12 The processes that occur during pseudorotaxane and
rotaxane formation are known to be quite sensitive to structure
and electronic environment. Therefore, small changes can cause
unexpectedly large effects as investigated earlier by kinetic
studies on the reverse reaction, i.e. the deslipping of axles with
stopper groups of intermediate sizes.13
aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustraße
3, 14195 Berlin, Germany. E-mail: christoph@schalley-lab.de;
Fax: (+49) 30-838-55817
bWilhelm-Ostwald-Institut für Physikalische und Theoretische Chemie
Universität Leipzig, Linnéstraße 2, 04103 Leipzig, Germany.
E-mail: bkirchner@uni-leipzig.de; Fax: (+49)341-9736399
cDepartment of Chemistry, Nanoscience Center, University of Jyväskylä,
P.O. Box 35, 40014 Jyväskylä, Finland
Jeong and co-workers14 have examined the binding of a dicar-
bonyl guest to TLMs similar to 1a (Scheme 1). In this study,
both hemispheres of the macrocycle were pyridine-2,6-dicarbox-
amides. Substituents at the position para to the pyridine nitrogen
atom cause strong electronic effects on the binding behaviour of
the TLM. This was rationalized by secondary effects15 and per-
turbations of the intramolecular hydrogen bonds between the
amide NH hydrogen atoms and the pyridine nitrogen. Therefore,
†This article is part of the Organic & Biomolecular Chemistry 10th
Anniversary issue.
‡Electronic supplementary information (ESI) available: Results from
NMR titrations and ITC measurements, crystallographic data, and theor-
etical calculations. CCDC 853879 and 853880. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/
c2ob25196e
5954 | Org. Biomol. Chem., 2012, 10, 5954–5964
This journal is © The Royal Society of Chemistry 2012

View Online
however, no experimental data supporting these calculations
have been reported.
This has encouraged us to investigate the structural and elec-
tronic effects of different substituents on the binding of diamide
axles to the unsymmetrically substituted TLM 1a (Scheme 1). In
order to obtain reliable data, NMR titrations were combined with
isothermal titration calorimetry (ITC) experiments. Sessler
et al.20 compared both methods for calix[4]pyrrole, which binds
ammonium salts in an ion-pair binding motif. They obtained
comparable Ka values as long as the binding constants are within
the dynamic ranges of both methods. This combination of
methods provides structural information on the binding motifs
from NMR experiments with detailed thermodynamic data from
ITC measurements and therefore is of great benefit for a com-
plete characterization of the pseudorotaxanes under study.21 The
experimental data are again accompanied with theoretical calcu-
lations employing density functional theory (DFT), along with
dispersion-corrected exchange-correlation functionals which
reflect the substituent effects and show similar trends as exper-
imentally observed.
Results and discussion
TLMs 1a,b (Scheme 1) were synthesized by an established lit-
erature procedure.22 Macrocycle 1a contains a pyridine-2,6-
dicarboxamide on one side whose N atom points into the cavity
and forms two intramolecular (pyridine)N⋯HN(amide) hydro-
gen bonds. They force the amide NH atoms to converge into the
cavity and thus provide preorganization for a better binding of
the axle’s carbonyl groups.23 The opposite hemisphere of 1a
contains an isophthaloyl diamide substituted with a solubility-
enhancing t-butyl group. On this side, one of the amide NH
groups can rotate outwards so that one wheel carbonyl group can
point into the cavity, if required by a guest. This conformational
change neither has a significant barrier nor causes any substantial
energy difference.24
The differently substituted diamide guest molecules 2–12
(Scheme 1) are available from simple one-step syntheses in good
to excellent yields. Starting from N,N′-dimethyl ethylene
diamine and the appropriately substituted acid chlorides, the
desired products are obtained in separate reactions after stirring
at room temperature in dichloromethane for 18 hours with NEt3
as the base. An exception is guest 9, which was synthesized in a
step-by-step approach (see Experimental section). These diamide
guests are known to bind non-covalently inside the cavity of 1a
—usually by forming four hydrogen bonds between the carbonyl
groups of the guest and the amide hydrogen atoms of 1a,b.25
Consequently, a threaded geometry results. Because no bulky
stopper groups terminate the axles, the association is reversible
on a fast time scale. Since diamide axles are insoluble in organic
solvents, when secondary amides are incorporated, their tertiary
amide analogues were used for this study. The better solubility,
however, comes at the price of higher conformational freedom,
because the cis- and trans-amide isomers equilibrate. The trans,
trans-isomer is the major isomer for the axles under study, but a
significant contribution from the trans, cis- and a minor amount
of the cis, cis-isomer is clearly visible in the axle NMR
spectra.26 Peak broadening at room temperature points to an
Scheme 1 (A) Binding motif of the pseudorotaxanes based on tetralac-
tam macrocycles 1a and 1b; (B) synthesis of axles 2–12 with different R
substituents and overview of diamide axles.
a nitro group attached to the pyridine ring increases the binding
strength significantly, while electron-donating groups reduce it.
A recent theoretical study16 systematically varied the substitu-
ents on a monoamide axle which is known to bind to Hunter/
Vögtle TLMs by three hydrogen bonds. Two wheel amides
donate one hydrogen bond each to the axle carbonyl group,
which in turn donates its amide NH hydrogen to bind to a third
amide carbonyl incorporated in the wheel. No significant substi-
tuent effects were observed, because the substituents alter the
binding properties of the three hydrogen bonds in a counterba-
lancing way. When the (axle)CvO⋯H–N(wheel) hydrogen
bonds are strengthened, the (axle)N–H⋯OvC(wheel) hydrogen
bond is weakened and vice versa. Thus, the substituents affect
the individual hydrogen bonding strengths, but overall the
effects more or less cancel each other. In marked contrast, a
second theoretical paper17 on pseudorotaxanes with different
diamide axles reported strong substituent effects on the total
interactions energies. Here, the binding situation is different,
since the TLM (in this case the smaller Leigh-type TLM)18
binds with all four amide NH groups to the two carbonyl groups
of the diamide axle and thus excludes a similar compensation
effect. Although the individual hydrogen bonds of the diamide
pseudorotaxanes are somewhat weaker than those of the monoa-
mide pseudorotaxanes, the calculations predict differences in the
total interaction energies of 20 kJ mol−1 between the strongest
and the weakest axle investigated. The individual hydrogen
bonding energies correlate nicely with N–H stretch vibrational
frequencies. Good linear correlations between these frequencies
and Hammett’s substituent constants19 were found. So far,
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 5954–5964 | 5955

View Online
interconversion of these isomers slow on the NMR time scale,
but close to the coalescence temperature. The binding constants
determined here thus are apparent binding constants.
Single crystals of pseudorotaxanes 2@1b and 8@1b suitable
for X-ray crystallography could be grown and their crystal struc-
tures were solved (Fig. 1 and ESI‡). In contrast to the other pseu-
dorotaxanes under study here, these pseudorotaxanes bear the
symmetrical wheel 1b with two t-butyl-substituted isophthaloyl
diamide moieties in the two hemispheres. Nevertheless, the two
structures are quite instructive with respect to the hydrogen
bonding connecting the wheel with the diamide stations of the
two axles. For 8@1b, four hydrogen bonds connect axle and
wheel (Fig. 1E). The N–O distances of 3.057 and 3.070 Å are in
a normal range as found earlier in crystal structures25a,27 of
rotaxanes and catenanes based on Hunter/Vögtle TLMs as well
as in theoretical calculations.24 Because of the zig-zag confor-
mation of the ethylene diamide spacer connecting the two axle
amide groups, the two axle carbonyl groups are unable to pos-
ition themselves exactly in the mirror plane through the two iso-
phthaloyl diamide groups of the macrocycle.
Consequently, the N–H⋯O hydrogen bond angles differ by
about 10°. The deviation of the carbonyl groups from the mirror
plane is also reflected in the (wheel)N–OvC(axle) angles that
are 113.5° and 139.8°. Thus, the structure of 8@1b is in good
agreement with expectation from earlier studies. The structure of
2@1b (Fig. 1A) exhibits some contrasting features: The two
(wheel)N–H⋯OvC(axle) hydrogen bonds in each hemisphere
are very different in length (3.002 vs. 3.299 Å). Consequently,
the axle forms two stronger and two weaker hydrogen bonds
with the wheel. While the N–H⋯O angles are not much smaller
than those of 8@1b, the two (wheel)N–OvC(axle) angles
describing the tilt of the axle carbonyls out of the wheel’s mirror
plane are drastically different. The shorter hydrogen bond corre-
sponds to an almost linear arrangement (<NOC = 171.1°), while
the longer one relates to an NOC angle of only 82.8°. The tilt of
the carbonyl group out of the plane is thus much larger in 2@1b
as compared to 8@1b. The packing of the two pseudorotaxanes
exhibits C–H⋯O and C–H⋯π interactions, respectively: one of
the vinyl hydrogen atoms at the terminal carbon atom of the axle
in 2@1b directly points towards a carbonyl oxygen atom of the
next neighbour’s wheel (Fig. 1B). With a value of 3.343 Å, the
C–O distance is quite short for a C–H⋯O hydrogen bond.
Instead, each of the phenyl rings of the axle in 8@1b has a
C–H⋯π contact with one of the aromatic rings in the wheel of
the next neighbour pseudorotaxane. The distance between the
C–H carbon atom and the centroid of the wheel’s aromatic ring
is 3.713 Å (Fig. 1F).
1
Fig. 2 shows the results of a typical H NMR titration exper-
iment. Upon stepwise addition of axle 2 to 1a, the two signals
for the four wheel amide NH protons shift upfield by 1.46 ppm
(py-NH) and 1.34 ppm (isoph-NH). Similarly, the proton at C(6)
of the isophthaloyl moiety feels the presence of the axle inside
the cavity of the wheel and shifts by 0.53 ppm to lower field.28
The 1 : 1 stoichiometry of the axle–wheel complex is confirmed
by the intersection of two lines fitted to the first and last four
data points of the titration curve, respectively. They cross at a
1 : 1 host–guest ratio. In contrast, the signals for the diamide axle
binding site, i.e. the axle NCH3 and NCH2 protons, shift to
higher field, because they feel the anisotropy of the aromatic
Fig. 1 (A) Ortep plot of the crystal structure of 2@1b (50% probability
level). (B) Packing of 2@1b highlighting short C–H⋯O contacts
between a vinyl H atom and a carbonyl O of the neighbor’s wheel. (C,
D) Space filling representations of 2@1b and 8@1b, respectively. (E)
Ortep plot of the crystal structure of 8@1b (50% probability level). (F)
Crystal packing of 8@1b highlighting C–H⋯π contacts between the
axle phenyl group and one of the wheel aromatic rings of a neighbouring
pseudorotaxane.
5956 | Org. Biomol. Chem., 2012, 10, 5954–5964
This journal is © The Royal Society of Chemistry 2012

View Online
Fig. 3 Shifts of the pyridine dicarboxamide NH signal of 1a during
titrations with aryl-substituted axles 6, 7, 8, 10 and 11 (CDCl3, 298 K).
Fig. 2 1H NMR titration of 1a with 2 (CDCl3, 298 K). The wheel’s
amide NH signals undergo significant complexation-induced low-field
shifts. Also, the inner isophthaloyl C–H experiences low-field shifts due
to the presence of the axle in the wheel’s cavity.
order of magnitude higher than the phenyl substituted axle 8.
This results in the binding free energies of 2 and 3 being higher
by ca. 6 kJ mol−1 than that of 8. (ii) In the series of aryl-substi-
tuted diamides, the binding constants depend significantly on the
electronic nature caused by the para-substituent. While electron-
withdrawing substituents reduce the binding free energies, elec-
tron-donating substituents increase them. The axles with the
strongest electron-withdrawing groups (e.g. NO2) exhibit only
vanishingly small binding constants; no binding was observed
for the pentafluorophenyl-substituted axle 12. Consequently,
template effects for rotaxane synthesis based on similar
diamide–TLM binding motifs can be modulated by substituent
effects affecting the hydrogen bond acceptor qualities of the axle
carbonyl groups.
Fig. 4 exemplarily shows the titration curves for the complexa-
tion of 2 and 8 to TLM 1a as obtained from complementary ITC
experiments. The determination of Ka, ΔH, ΔG, and ΔS is simul-
taneously possible in a single experiment so that all relevant
thermodynamic binding parameters can be obtained.30 An
important parameter for ITC experiments of low affinity systems
is the so-called Wiseman “c” value, which is the product of the
total host concentration and the binding constant Ka (eqn (2)).31
For c < 10, ITC experiments become challenging. In this
equation, n is the number of binding sites in the receptor with
n = 1 for the pseudorotaxanes under study here. One way to
compensate for low affinity binding would be to increase the
total concentration of the macrocycle. Unfortunately, the solubi-
lity of TLM 1a limits this approach here. An earlier report32 on
alkali metal ion binding to crown ethers, however, confirmed
that ITC measurements still provide reliable data even when c is
small and the titration curves are not sigmoidal in shape provided
that the following requirement is met: a sufficiently large part of
the binding isotherm with sufficient signal-to-noise must be used
for analysis. Also, the stoichiometry of the complex formed must
be clear and the concentrations of both host and guest must be
precisely known.
rings incorporated in the wheel’s walls. These complexation-
induced shifts clearly confirm that the axle binds inside the
wheel cavity by hydrogen bond formation between the wheel’s
amide NH hydrogen atoms and the axle’s carbonyl oxygen
atoms. Axle 4 can be used as a control to confirm the threaded
geometry of the pseudorotaxanes under study: the two bulky
trityl groups prevent slipping of this axle into the cavity so that
either no or very different NMR signal shifts are expected. For
this axle, only very minor shifts (Δδ < 0.1 ppm) of the wheel’s
amide NH hydrogen atoms are observed. Also, the axle NCH2
and NCH3 protons do not shift during the titration. These results
thus indicate the axle to be only weakly bound—if at all—at the
macrocycle periphery outside the cavity.
From the curvature of the titration curve (ESI‡), the binding
constant was determined by non-linear curve fitting based on
eqn (1) and a 1 : 1 binding model.29 In this equation, δobs is the
observed shift of the py-NH signals of the macrocycle at each
titration step as a function of the initial concentrations of macro-
cycle [M]0 and guest [G]0. δ0 is the chemical shift of the free
macrocycle and Δδmax is the difference between the theoretical
signal shift at 100% complexation and δ0.
ꢀ
Δδmax
1
δobs ¼ δ0 þ
þ ½Mꢀ0 þ ½Gꢀ0ꢁ
2½Mꢀ0 Ka
3
5
sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
ꢁ
ꢂ
ð1Þ
ð2Þ
þ ½Mꢀ0 þ ½Gꢀ0 2ꢁ4½Mꢀ0½Gꢀ0
1
Ka
c ¼ nka½Mꢀ0
The same procedure was carried out for pseudorotaxanes
3@1a–12@1a and the titration curves for the series of aryl-sub-
stituted axle derivatives 6–8, 10 and 11 are summarized in
Fig. 3. The resulting binding data are listed in Table 1. Two con-
clusions can be drawn from the NMR titration data. (i) Axles
with alkyl (3) or alkenyl groups (2) attached to the diamide car-
bonyl groups have the highest binding constants among the
axles under study. With about 4000 M−1, they are roughly one
Making sure that these conditions are met, the binding free ener-
gies obtained from the ITC experiments (Table 1) agree well with
those extracted from the NMR titrations within 1.5 kJ mol−1
which corresponds to ca. 10% of the total binding energies. Con-
sequently, the conclusions drawn from the NMR data above are
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 5954–5964 | 5957

View Online
Table 1 Thermodynamic data obtained from the NMR titrations and ITC measurements with pseudorotaxanes formed from TLM 1a and guests
2–12. NMR titrations and ITC measurements were performed at 25 °C
NMR titrationsa
Ka [M−1
ITC experimentsa
Ka [M−1
Axle
Hammett constant σ
]
ΔG [kJ mol−1 b
]
]
ΔH [kJ mol−1
]
−TΔS [kJ mol−1
]
ΔG [kJ mol−1 b
]
2
3
4
5
6
7
8
9
4000 400
3800 400
−20.6 0.3
−20.4 0.3
3500 400
2300 300
No binding observed
490 50
−38.2 2.0
−14.5 0.8
18.0 2.3
−4.7 1.1
−20.2 0.3
−19.2 0.3
610 70
460 50
380 40
370 40
280 30
<20
−15.9 0.3
−15.2 0.3
−14.7 0.3
−14.7 0.3
−14.0 0.3
<−7.4
−24.9 1.3
−18.9 1.0
−29.6 1.5
−22.9 1.2
−32.5 1.7
−19.8 1.0
9.5 1.6
3.4 1.3
13.6 1.8
8.4 1.5
19.5 2.0
8.6 1.3
−15.4 0.3
−15.5 0.3
−16.0 0.3
−14.5 0.3
−13.0 0.3
−11.2 0.3
−0.27
−0.20
0.00
510 60
640 70
350 40
190 20
10
11
12
0.43
0.78
90 10
<10
<−5.7
No binding observed in ITC experiments
No binding observed
a Since NMR and ITC are different methods with respect to optimal concentration regimes and the primary information obtained, some deviations of
the data can be expected as discussed earlier by Sessler et al.20a b Calculated with ΔG = −RT ln Ka.
Fig. 4 ITC experiments (heat flow versus time and heat/volume versus
guest/TLM ratio; CHCl3, 298 K) of (A) axle 2 and (B) axle 8 with TLM
1a.
Fig. 5 Structure of 8@1a optimized at the B97-D level of theory with
the TZVP basis set. For the calculated structures of the other aryl-substi-
tuted pseudorotaxanes, see ESI.‡
confirmed by the ITC data. Since the ITC experiments also
provide binding enthalpies and binding entropies, a more
detailed picture is obtained here. Axle 3 with the two long,
flexible alkyl chains directly attached to the amide carbonyl
groups has quite a low binding enthalpy, but a favorable positive
binding entropy thus indicating the complexation to be signifi-
cantly supported by entropic effects. In marked contrast, all axles
that carry phenyl derivatives attached to the amide carbonyls, as
well as axle 2 with the short alkenyl substituent, reveal approxi-
mately two times larger negative binding enthalpies, while all
binding entropies are negative. Binding is clearly driven by
enthalpy in these cases. Similar data were obtained for monoa-
mide binding in a related TLM.16 We attribute the differences in
binding entropies to solvent effects. The negative binding entro-
pies for the aryl-substituted diamide axles are in line with the
combination of two particles into one complex. The positive
entropy for 3@1a is then due to an overcompensation of this
effect by differences in solvation.33
The substituent effects on the binding free energies have been
investigated theoretically by density functional calculations at
the B97-D/TZVP level. The structures of pseudorotaxanes with
symmetrical aryl-substituted axles (6@1a–8@1a and 10@1a–
12@1a) were optimized starting from a geometry in which the
diamide station was bound to the wheel by four (wheel)N–
H⋯OvC(axle) hydrogen bonds. The optimized structure of
8@1a is shown in Fig. 5 as a representative example. Hydrogen
bond lengths and N–H⋯O angles are summarized in Table 2.
The two hydrogen bonds formed to the pyridine dicarboxamide
moiety are similar in length (3.01 and 3.02 Å) and somewhat
shorter and likely somewhat stronger than the two hydrogen
5958 | Org. Biomol. Chem., 2012, 10, 5954–5964
This journal is © The Royal Society of Chemistry 2012

View Online
Table 2 Calculated hydrogen bond lengths and angles, adiabatic interaction energies ΔEadia, energies ΔECF calculated for the conformational change
of wheel and axle upon binding, and shared-electron number SEN for the series of pseudorotaxanes with symmetrically aryl-substituted axles (for
definitions, see theoretical section). The four hydrogen bonds between axle are denoted “py1/2” for those in the pyridine dicarboxamide hemisphere
and “iso1/2” for those in the isophthaloyl diamide hemisphere. “py1” and “iso1” diametrically oppose each other in the calculated structures
N–H⋯O hydrogen bond lengths [Å]
N–H⋯O hydrogen bond angles [o]
ΔEadia
ΔECF
SENa
σtotal [e]
Axle
py1
py2
iso1
iso2
py1
py2
iso1
iso2
[kJ mol−1
]
[kJ mol−1
]
6
7
8
10
11
12
2.92
3.03
3.02
3.04
3.03
3.10
3.12
2.99
3.01
3.08
3.09
4.37b
2.91
3.15
3.15
3.15
3.25
3.16
2.95
3.11
3.10
3.09
3.11
3.81b
145.5
146.0
144.6
140.3
141.7
133.3
148.7
146.9
146.6
144.6
145.6
154.7
158.3
162.7
162.1
160.1
161.2
146.5
155.0
149.2
147.8
147.3
145.4
163.0
−194.4
−193.5
−182.1
−180.5
−178.4
−131.3
−40.6
−28.7
−25.9
−28.2
−25.9
−35.7
0.1206
0.0803
0.0770
0.0688
0.0626
0.0235
a The shared-electron numbers for the individual hydrogen bonds are given in the ESI.‡ b These N–O distances are too long to count as hydrogen
bonds and likely do not contribute significantly to the binding.
ΔESEN ¼ m ꢂ σHA þ b
ð5Þ
bonds formed with the isophthaloyldiamide group (3.15 and
3.10 Å). All four distances are nevertheless in the expected
range (see above). Thus, the tilt of the axle carbonyl group is
more pronounced in the isophthaloyldiamide hemisphere of the
complex as indicated also by the larger differences in N–H⋯O
hydrogen bond angles on that side of the pseudorotaxane. In
addition, also the angles are within the expected range. The
other calculated structures do not deviate much from these
values with one exception. The most weakly bound pseudorotax-
ane, i.e. the pentafluorophenyl-substituted axle 12, forms only
two hydrogen bonds. For the py2 and iso2 hydrogen bonds
(Table 2), the N–O distances are 3.81 and 4.37 Å so we can
safely assume these do not contribute significantly to the
binding.
Finally, the trend in substituent effects is also supported by the
shared-electron numbers (SEN) for the hydrogen bonds between
axles and wheels (also, see ESI‡). The SEN provides a semi-
quantitative measure of the hydrogen bond strengths, because
the linear relationship in eqn (5) exists, in which σHA represents
the two-centre shared electron number of a hydrogen bond and
ΔESEN its binding energy. Even if one does not determine the
slope and intercept, which differ with acceptor atom and the
combination of functional and basis set, trends can easily be
determined from the SEN values. From the data given in
Table 2, the trend to stronger binding with more electron-donat-
ing substituents is clearly visible.
In order to study the substituent effects on the binding ener-
gies theoretically, the adiabatic interaction energies ΔEadia were
calculated according to eqn (3), in which Etotal is the total energy
calculated for the complex, Erelaxed the total energies of the two
components in their conformationally relaxed geometries and
ΔEBSSE the basis set superposition error. The absolute values
given in Table 2 are much higher than the experimental data.
This, however, does not come as a surprise,16 because the calcu-
lations do not involve competition of the axle with the solvent
for binding inside the cavity of the TLM. More relevant are the
substituent-dependent differences, which follow the same trend
as the experimental values. More electron-donating axle substitu-
ents result in higher binding energies, because they increase the
donor strengths of the axle carbonyl oxygen atoms and thus
improve their hydrogen-bond acceptor qualities. Upon binding,
both the wheel and the axle rearrange with respect to their con-
formations to some extent in order to mutually accommodate the
binding partner. The ΔECF values in Table 1 (eqn (4)) provide an
estimate of the rearrangement energy necessary to bring the
wheel and axles from their relaxed conformations into the struc-
ture which they finally have in the complex. With values
between −25 and −40 kJ mol−1, these rearrangement energies
are quite substantial.
Conclusions
In conclusion, the choice of the substituents at the diamide axle
changes the binding properties in several ways and can thus be
utilized to fine-tune the binding properties. First, the alkyl- and
alkenyl-substituted diamides bind with binding constants higher
than the aryl-substituted axles by an order of magnitude. Second,
the binding is driven by enthalpic effects, if the axle carries sub-
stituents with π-systems attached to the amide carbonyl groups.
Only the formation of pseudorotaxane 3@1a with alkyl chains at
the carbonyl carbon atoms is due to positive binding entropies.
Third, within the series of differently substituted aryl diamides,
the electronic substituent effects are important for the formation
of pseudorotaxanes. Electron-withdrawing substituents diminish
the binding constants as compared to electron-donating substitu-
ents. The trends of binding energies thus follow the Hammett
substituent parameters.
The experimental and theoretical results nicely agree with
respect to the electronic substituent effects and thus have an
impact on the design of template effects for rotaxane synthesis.
For example, it would be advantageous to elongate the axles for
stopper attachment through ether linkages at the phenyl-C(4)
rather than using esters or amides. Ethers would enhance the
templating ability, while esters or amides would almost lead to
the loss of the non-covalent connections between wheel and axle
during rotaxane formation.
ΔEadia ¼ Ecomplex ꢁ Ewheel
relaxed ꢁ E
ꢁ ΔEBSSE
ð3Þ
ð4Þ
axle
relaxed
total
wheel
relaxed
axle
relaxed
axle
unrelaxed
ΔECF ¼ ðEwheel
relaxed ꢁ E
Þ þ ðE
ꢁ E
Þ
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 5954–5964 | 5959

View Online
Our study complements an earlier study by Jeong et al.14 who
reported substituent effects on the ability of TLMs to bind the
same diamide station. The changes found in our study are not as
drastic as those reported by Jeong and coworkers, but they are
still substantial. Furthermore, our binding data lends support to a
recent theoretical study.17 Even though a slightly different TLM
was used for the calculated binding data, the trends are well
confirmed in our study by experiment.
(singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br
(broad). Titration experiments were carried out in CDCl3
at 25 °C on a Bruker ECX 400 instrument. Solutions of 1a
(c = 5 mM, 0.6 mL) were placed in NMR tubes and treated with
various amounts of the guests 2–12 (c = 50 mM). After each
1
injection, a H NMR spectrum was recorded immediately. The
true guest concentrations in the solution under study were deter-
mined by integration of the signals for the wheel versus the inte-
gration of the signals for guest protons. The binding constants
were determined based on 1 : 1 binding model by fitting the
experimental data with eqn (1). Nonlinear curve fitting was
achieved with the tools implemented in IgorPro (Wavemetrics
Inc., Lake Oswego, Oregon/USA).
The present report is one of few which directly compare
binding data from NMR titrations with ITC results and theoreti-
cal calculations. The pseudorotaxanes under study exhibit
binding constants at the lower end of the ITC dynamic range,
which is roughly between 102 M−1 < Ka < 107 M−1, and thus
belong to the low-affinity systems, which do not fulfil the
broadly accepted requirement that Wiseman’s c value should be
larger than 10. Nevertheless, the data obtained from both
methods reveals quite good agreement. In line with a previous
report on alkali metal ion/crown ether binding,32 we conclude
that these low-affinity systems can be studied by isothermal titra-
tion calorimetry. On the one hand, the combination of both
methods is advantageous, because they overlap in yielding
binding free energies, which can be directly compared and—in
the case of good agreement—provides more confidence in the
data. On the other hand, both methods contribute their individual
share to the understanding of complex formation. While struc-
tural information can be extracted from NMR experiments, ITC
measurements directly provide binding enthalpies and binding
entropies. Otherwise, the determination of these two values
would require the much higher effort of temperature-dependent
NMR titrations.
Mass spectrometry
Samples were measured on an Agilent 6210 ESI-TOF, Agilent
Technologies, Santa Clara, CA, USA, with methanol as the spray
solvent. The solvent flow rate was adjusted to 4 μL min−1 and
the spray voltage set to 4 kV. The drying gas flow rate was
adjusted to 15 psi (1 bar). All other parameters were optimized
for a maximum abundance of the [M + Na]+ ions.
Isothermal titration calorimetry (ITC)
Titration experiments were carried out in CHCl3 at 298 K on a
TAM III microcalorimeter (Waters GmbH, TA Instruments,
Eschborn, Germany). In a typical experiment, an 800 μL sol-
ution of 1a was placed in the sample cell at a concentration of
2 mM, and 250 μL of one of the guests 2–12 were in the injec-
tion syringe at a concentration of 40 mM in the same solvent.
The titration schedule consisted of 25 consecutive injections of
8 μL with a 5 min interval between injections. Heats of dilution,
measured by titration of the guest into the sample cell with blank
solvent, were subtracted from each data set. All solutions were
degassed prior to titration. Titrations were repeated twice. The
data were analyzed using the instrumental internal software
package and fitted with a one-site binding model.
Experimental section
General methods
Reagents were purchased from Aldrich, ACROS or Fluka and
used without further purification. TLMs 1a,b were synthesized
according to literature procedures.22 The acid chloride for the
synthesis of guest 4 was obtained from the corresponding tri-
phenyl acetic acid by reaction with oxalyl chloride and a few
drops of dry DMF in CH2Cl2. After a clear solution formed
while stirring the reaction mixture at r.t., the solvents were evap-
orated under reduced pressure and the residue was used without
further purification. All other acid chlorides were commercially
available and used as purchased. Yields refer to chromatographi-
cally and spectroscopically homogeneous materials. Solvents
were dried and distilled prior to use by usual laboratory
methods. Thin-layer chromatography (TLC) was performed on
precoated silica gel 60/F254 plates (Merck KGaA). Silica gel
(0.04–0.063 mm; Merck) was used for column chromatography.
General procedure for the synthesis of the diamide guests (2–8,
10–12)
Under argon, N,N′-dimethylethylenediamine (300 mg,
3.4 mmol) was dissolved in 30 mL CH2Cl2 and treated with
1.5 mL NEt3. A solution of acid chloride (7.0 mmol) in 20 mL
CH2Cl2 was slowly added and the resulting solution was stirred
at r.t. for 18 h. The solvent was then evaporated and the products
were isolated by column chromatography (silica gel, pure
CH2Cl2 to CH2Cl2–acetone 2 : 1 or pure EtOAc).
NMR spectroscopy and NMR titrations
Synthesis of the diamide guest (9)
1H (400 MHz), 19F (376 MHz) and 13C (100 MHz) spectra were
obtained on a Bruker ECX 400 instrument at 298 K. All chemi-
cal shifts are reported in ppm with signals of CHCl3 (7.26 ppm
(1H) and 77.0 ppm (13C)) or CCl3F (0 ppm (19F)) taken as
internal standards; coupling constants are in Hz. The following
abbreviations were used to indicate NMR multiplicities: s
Under argon, N,N′-dimethylethylene diamine (300 mg,
3.4 mmol) was dissolved in 30 mL CH2Cl2 and treated with
1.5 mL NEt3. A solution of 4-methoxybenzoyl chloride
(2.72 mmol) in 10 mL CH2Cl2 was slowly added and the result-
ing solution was stirred at r.t. for 4 h. After that, a solution of 4-
trifluoromethylbenzoyl chloride (2.72 mmol) in 10 mL CH2Cl2
5960 | Org. Biomol. Chem., 2012, 10, 5954–5964
This journal is © The Royal Society of Chemistry 2012

View Online
N,N′-(Ethane-1,2-diyl)bis(4-methoxy-N-methylbenzamide) 6
was again slowly added and the resulting solution was left stir-
ring at r.t. for another 14 h. The solvent was then evaporated and
the product was isolated by column chromatography (preparative
TLC, silica gel, CH2Cl2–EtOAc 1 : 1).
White powder (1.16 g, 96%); Rf = 0.78 (CH2Cl2–acetone 2 : 1);
1H NMR (400 MHz, CDCl3): δ = 2.75–3.04 (br m, 6H; NCH3),
3
3.39–3.80 (br m, 10H; NCH2, OCH3), 6.79 (d, J = 6.3 Hz, 4H;
ArH), 7.28–7.38 ppm (m, 4H; ArH); 13C NMR (100 MHz,
CDCl3): δ = 37.8, 55.1 (CH3), 44.3 (CH2), 113.3, 128.6 (Ar–
CH), 128.2, 160.3 (Ar–Cq), 171.6 ppm (CvO); ESIMS: m/z
(%): 379.2 (100) [M + Na]+; HRMS (ESI+): m/z calcd for
C20H24N2O4Na+: 379.1634 [M + Na]+; found: 379.1641 (Δ =
1.9 ppm).
N,N′-(Ethane-1,2-diyl)bis(N-methylacrylamide) 2
Yellow oil (0.33 g, 50%); Rf = 0.34 (EtOAc); 1H NMR
(400 MHz, CDCl3): δ = 3.03, 3.04, 3.12 (3 s, 6H; NCH3),
3.51–3.62 (3 s, 4H; NCH2), 5.63–5.68 (m, 2H; CHvCH2),
6.26–6.35 (m, 2H; CHvCH2), 6.46–6.65 ppm (m, 2H;
CHvCH2); 13C NMR (100 MHz, CDCl3): δ = 34.2, 36.1, 37.4
(CH3), 45.1, 47.3, 47.6 (CH2), 127.0, 127.2, 127.8, 127.9,
128.4, 128.7 (CH2, CH), 166.8 ppm (CvO); ESIMS: m/z (%):
219.1 (100) [M + Na]+; HRMS (ESI+): m/z calcd for
C26H48N2O2Na+: 219.1104 [M + Na]+; found: 219.1107 (Δ =
1.4 ppm).
N,N′-(Ethane-1,2-diyl)bis(4-(t-butyl)-N-methylbenzamide) 7
White powder (1.22 g, 88%); Rf = 0.81 (CH2Cl2–acetone 2 : 1);
1H NMR (400 MHz, CDCl3): δ = 1.29 (s, 18H; tBu-H),
2.77–3.09 (br m, 6H; NCH3), 3.60–3.87 (br m, 4H; NCH2),
7.31–7.39 ppm (m, 10H; ArH); 13C NMR (100 MHz, CDCl3): δ
= 31.1, 34.7 (CH3), 37.9 (Cq), 44.4 (CH2), 125.1, 126.7 (Ar–
CH), 133.3, 152.6 (Ar–Cq), 172.0 ppm (CvO); ESIMS: m/z
(%): 431.3 (100) [M + Na]+; HRMS (ESI+): m/z calcd for
C26H36N2O2Na+: 431.2675 [M + Na]+; found: 431.2687 (Δ =
2.8 ppm).
N,N′-(Ethane-1,2-diyl)bis(N-methylundec-10-enamide) 3
Yellow oil (0.95 g, 67%); Rf = 0.12 (CH2Cl2), 0.98 (CH2Cl2–
1
acetone 2 : 1); H NMR (400 MHz, CDCl3): δ = 1.34 (br, 16H;
CH2), 1.39–1.44 (m, 4H; CH2), 1.53–1.62 (m, 4H; CH2), 2.06
(q, J = 7.3 Hz, 4H; CH2), 2.29 (m, 4H; CH2), 2.96, 3.06, 3.08
N,N′-(Ethane-1,2-diyl)bis(N-methylbenzamide) 8
3
White powder (0.89 g, 88%); Rf = 0.73 (CH2Cl2–acetone 2 : 1);
1H NMR (400 MHz, CDCl3): δ = 2.58–3.08 (br m, 6H; NCH3),
3.22–3.77 (br m, 4H; NCH2), 7.06–7.26 ppm (m, 10H; ArH);
13C NMR (100 MHz, CDCl3): δ = 37.4 (CH3), 44.0 (CH2),
126.4, 127.9, 129.0 (Ar–CH), 135.9 (Ar–Cq), 171.5 ppm
(CvO); ESIMS: m/z (%): 319.1 (100) [M + Na]+; HRMS
(ESI+): m/z calcd for C18H20N2O2Na+: 319.1417 [M + Na]+;
found: 319.1423 (Δ = 1.9 ppm).
(3 s, 6H; NCH3), 3.54, 3.57, 3.60 (3 s, 4H; NCH2), 4.91–5.02
(m, 4H; CHvCH2), 5.77–5.87 ppm (m, 2H; CHvCH2); 13C
NMR (100 MHz, CDCl3): δ = 25.1, 27.5, 29.0, 29.2, 29.4, 29.5,
29.6, 33.9, 35.7, 44.6 (CH2, CH3), 114.2 (CH2), 139.3 (CH),
173.6 ppm (CvO); ESIMS: m/z (%): 443.4 (100) [M + Na]+;
HRMS (ESI+): m/z calcd for C26H48N2O2Na+: 443.3608 [M +
Na]+; found: 443.3605 (Δ = −0.7 ppm).
4-Methoxy-N-methyl-N-(2-(N-methyl-4-(trifluoromethyl)-
benzamido)ethyl)benzamide 9
N,N′-(Ethane-1,2-diyl)bis(N-methyl-2,2,2-triphenylacetamide) 4
White powder (1.13 g, 53%); Rf = 0.10 (CH2Cl2), 0.95
1
White powder (0.41 g, 31%); Rf = 0.48 (CH2Cl2–EtOAc 1 : 1);
1H NMR (400 MHz, CDCl3): δ = 3.08–3.15 (br m, 6H; NCH3),
3.80–3.92 (br m, 7H; NCH2, OCH3), 6.87 (d,3J = 7.8 Hz, 2H;
(CH2Cl2–acetone 2 : 1); H NMR (400 MHz, CDCl3): δ = 2.42
(s, 6H; NCH3), 3.62 (s, 4H; NCH2), 7.19–7.31 ppm (m, 30H;
ArH); 13C NMR (100 MHz, CDCl3): δ = 38.5 (CH3), 53.4
(CH2), 67.3 (Cq), 126.6, 127.7, 130.1 (Ar–CH), 142.8 (Ar–Cq),
173.0 ppm (CvO); ESIMS: m/z (%): 651.3 (100) [M + Na]+;
HRMS (ESI+): m/z calcd for C44H40N2O2Na+: 651.2982 [M +
Na]+; found: 651.2986 (Δ = 0.6 ppm).
3
3
ArH), 7.37 (d, J = 7.8 Hz, 2H; ArH), 7.51 (d, J = 8.1 Hz, 2H;
ArH), 7.64 ppm (d, 3J = 8.1 Hz, 2H; ArH); 13C NMR
(100 MHz, CDCl3): δ = 37.8, 55.0 (CH3), 44.4 (CH2), 113.4,
125.3, 126.9, 128.7 (Ar–CH), 122.3, 128.1, 139.7, 141.1, 160.3
(Cq, Ar–Cq), 170.4, 171.2 ppm (CvO); 19F NMR (376 MHz,
CDCl3): δ = −62.8 ppm (s, 6F; CF3); ESIMS: m/z (%): 417.1
(100) [M
+
Na]+; HRMS (ESI+): m/z calcd for
C20H21F3N2O3Na+: 417.1402 [M + Na]+; found: 417.1413 (Δ =
N,N′-(Ethane-1,2-diyl)bis(N-methylnaphthamide) 5
2.6 ppm).
White powder (0.62 g, 46%); Rf = 0.79 (CH2Cl2–acetone 2 : 1);
1H NMR (400 MHz, CDCl3): δ = 3.16 (br, 6H; NCH3), 3.97 (br,
4H; NCH2), 7.47–7.49 (m, 6H; ArH), 7.78–7.91 ppm (m, 8H;
ArH); 13C NMR (100 MHz, CDCl3): δ = 37.8 (CH3), 44.4
(CH2), 67.3 (Cq), 112.1, 124.0, 126.4, 126.5, 126.8, 127.6,
128.0, 128.2, 132.5, 133.4 (Ar–CH, Ar–Cq), 171.8 ppm (CvO);
ESIMS: m/z (%): 419.2 (100) [M + Na]+; HRMS (ESI+): m/z
calcd for C26H24N2O2Na+: 419.1730 [M + Na]+; found:
419.1736 (Δ = 1.4 ppm).
N,N′-(Ethane-1,2-diyl)bis(N-methyl-4-(trifluoromethyl)-
benzamide) 10
White powder (1.37 g, 93%); Rf = 0.69 (CH2Cl2–acetone 2 : 1);
1H NMR (400 MHz, CDCl3): δ = 3.06 (br s, 6H; NCH3), 3.90
3
(br s, 4H; NCH2), 7.48 (d, J = 8.2 Hz, 4H; ArH), 7.61 ppm (d,
3J = 7.9 Hz, 4H; ArH); 13C NMR (100 MHz, CDCl3): δ = 37.7
Org. Biomol. Chem., 2012, 10, 5954–5964 | 5961
This journal is © The Royal Society of Chemistry 2012

View Online
(CH3), 44.7 (CH2), 125.5, 127.1 (Ar–CH), 122.9, 124.5, 139.8
(Cq, Ar–Cq), 170.7 ppm (CvO); 19F NMR (376 MHz, CDCl3):
δ = −62.8 ppm (s, 6F; CF3); ESIMS: m/z (%): 455.1 (100) [M +
Na]+; HRMS (ESI+): m/z calcd for C20H18F6N2O2Na+: 455.1170
[M + Na]+; found: 455.1153 (Δ = −3.7 ppm).
monoclinic, space group C2/c, a = 25.976(5) Å, b = 19.610(4)
Å, c = 19.930(4) Å, β = 126.21(3)°, V = 8191(3) Å3, Z = 4, Dc =
1.259 g cm−3, F000 = 3288, μ = 0.266 mm−1, T = 123(2) K,
2θmax = 25°, 7156 independent reflections, 4611 with Io
>
2σ(Io), Rint = 0.1102, 480 parameters, 0 restraints, GoF = 1.046,
R = 0.0695 [Io > 2σ(Io)], wR = 0.1742 (all reflections), 0.380 <
Δρ < −0.478 eÅ3.
N,N′-(Ethane-1,2-diyl)bis(N-methyl-4-nitrobenzamide) 11
Yellow powder (1.16 g, 89%); Rf = 0.65 (CH2Cl2–acetone 2 : 1);
1H NMR (400 MHz, CDCl3): δ = 3.01 (br s, 6H; NCH3), 3.89
(br s, 4H; NCH2), 7.50 (d, J = 8.9 Hz, 4H; ArH), 8.16 ppm (d,
Theoretical section
3
The structure of all complexes were optimised using density
functional theory (DFT) combined with the resolution of identity
technique (RI).40 The TZVP basis set was applied in combi-
nation with the general gradient approximated type functional
B97-D with dispersion correction developed by Grimme.41 All
calculations were performed using the TURBOMOLE 6.0
program package.42 The obtained complex interaction energies
were counterpoise-corrected by the method introduced by Boys
and Bernardi.43 According to the supramolecular approach, the
adiabatic complex interaction energies ΔEad can be calculated by
subtracting the energies of the relaxed wheel Erel(wheel) and
axle Erel(guest) as well as the BSSE contributions to the total
cluster energy Etot(complex) as given in eqn (3). Because of
complex formation, the conformation of the molecules changes.
The energy ΔECF related to this conformational change does not
directly contribute to the hydrogen bond energies. Therefore,
ΔECF was calculated according to eqn (4). We also carried out
the computation of the two-center shared electron number
(SEN).42 The determination of the two-centre shared electron
3J = 8.9 Hz, 4H; ArH); 13C NMR (100 MHz, CDCl3):δ = 37.6
(CH3), 44.7 (CH2), 123.7, 127.6 (Ar–CH), 142.3, 148.1 (Ar–
Cq), 169.7 ppm (CvO); ESIMS: m/z (%): 409.1 (100) [M +
Na]+; HRMS (ESI+): m/z calcd for C18H18N4O6Na+: 409.1124
[M + Na]+; found: 409.1133 (Δ = 2.2 ppm).
N,N′-(Ethane-1,2-diyl)bis(pentafluoro-N-methylbenzamide) 12
1
Orange powder (1.49 g, 92%); Rf = 0.14 (CH2Cl2); H NMR
(400 MHz, CDCl3): δ = 3.04 (br s, 6H; NCH3), 3.87 ppm (br s,
4H; NCH2); 13C NMR (100 MHz, CDCl3): δ = 36.6 (CH3), 44.8
(CH2), 111.1, 136.4, 138.9, 140.7, 141.5, 144.0 (Ar–Cq),
159.2 ppm (CvO); 19F NMR (376 MHz, CDCl3): δ = −159.4
(m, 4F; ArF), −151.4 (m, 2F; ArF), −141.9 ppm (m, 4F; ArF);
ESIMS: m/z (%): 499.1 (100) [M + Na]+; HRMS (ESI+): m/z
calcd for C18H10F10N2O2Na+: 499.0475 [M + Na]+; found:
499.0497 (Δ = 4.4 ppm).
number is based on the population analysis by Davidson.44
A
linear relationship (eqn (5)) exists between the two-center
shared-electron number of a hydrogen bond σHA and its binding
energy which allows an estimation of the bond strength. There-
fore, the slope m and the axis intercept b of eqn (5) need to be
determined, because they depend on the acceptor atom of the
hydrogen bonds and the combination of functional and basis set.
It is well known that this procedure works for a broad variety of
chemical applications concerning hydrogen bonds.45 To get
qualitative results on the bonding strength, a comparison of the
two center shared electron number σHA is sufficient.
Crystallographic section
Colorless crystals of 2@1b and 8@1b were obtained by diffu-
sion of ether into a saturated chloroform solution of host and
guest. The structural analysis was performed using Bruker-
Nonius Kappa Apex II diffractometer with graphite-monochro-
matized Cu-Kα (λ = 1.54183 Å) radiation at 173 K for 2@1b
and Bruker-Nonius Kappa Apex II diffractometer with graphite-
monochromatized Mo-Kα (λ = 0.71073 Å) radiation at 123 K
for 8@1b. Collect software34 was used for the data measurement
and DENZO-SMN35 for the processing. The structures were
solved by charge flipping method with SUPERFLIP36 and
refined by full-matrix least-squares methods using the WinGX-
software,37 which utilizes the SHELXL-97 module.38 Multi-scan
absorption correction was done by SADABS2008.39 All C–H
hydrogen positions were calculated using a riding atom model
Acknowledgements
This research has been funded by the Deutsche Forschungsge-
meinschaft (SFB 765 and grant KI-768/7-1), the German Aca-
demic Exchange Service (DAAD), the Finnish Academy (KR
proj. no. 130629, 122350, 140718) and the Fonds der Che-
mischen Industrie (FCI). L.K. and E.V.D. are deeply indebted to
the Studienstiftung des deutschenVolkes (German National Aca-
demic Foundation) for doctoral scholarships. We thank Antti
Senf, B.Sc. for synthesising the wheel used in this study and Dr.
Christian Ortmann (Waters GmbH) for help with the interpret-
ation of the ITC experiments.
with UH
= 1.2 × UC. All non-H atoms were refined
anisotropically.
Crystal data for 2@1b (CCDC-853879): colorless blocks,
0.15 × 0.20 × 0.25 mm, FW = 1691.08, C82H100N6O6Cl12, tricli-
ˉ
nic, space group P1, a = 13.087(3) Å, b = 13.192(2) Å, c =
14.620(3) Å, α = 103.23(2)°, β = 107.21(3)°, γ = 108.81(2)°, V
= 2131(1) Å3, Z = 1, Dc = 1.318 g cm−3, F000 = 886, μ =
3.998 mm−1, T = 173(2) K, 2θmax = 63.31°, 6843 independent
reflections, 5265 with Io > 2σ(Io), Rint = 0.1111, 485 parameters,
0 restraints, GoF = 1.038, R = 0.0758 [Io > 2σ(Io)], wR = 0.2160
(all reflections), 0.692 < Δρ < −0.501 eÅ3.
Notes and references
1 (a) J.-M. Lehn, Supramolecular Chemistry – Concepts and Perspectives,
Wiley-VCH, Weinheim, 1996; (b) Molecular Catenanes, Rotaxanes and
Knots, ed. J.-P. Sauvage and C. O. Dietrich-Buchecker, Wiley-VCH,
Crystal data for 8@1b (CCDC-853880): colorless blocks,
0.10 × 0.15 × 0.35 mm, FW = 1552.46, C88H102N6O6Cl6,
5962 | Org. Biomol. Chem., 2012, 10, 5954–5964
This journal is © The Royal Society of Chemistry 2012

View Online
Weinheim, 1999; (c) N. V. Gerbeleu, V. B. Arionand and J. Burgess, Tem-
plate Synthesis of Macrocyclic Compounds, Wiley-VCH, Weinheim,
1999; (d) Templated Organic Synthesis, ed. F. Diederich, P. Stang, Wiley-
VCH, Weinheim, 2000; (e) Molecular Motors, ed. M. Schliwa, Wiley-
VCH, Weinheim, 2003; (f) V. Balzani, M. Venturi and A. Credi, Molecu-
lar Devices and Machines. A Journey into the Nano World, Wiley-VCH,
Weinheim, 2003; (g) J. W. Steed, D. R. Turner and K. Wallace, Core Con-
cepts in Supramolecular Chemistry and Nanochemistry, Wiley, 2007;
(h) V. Balzani, A. Credi and M. Venturi, Molecular Devices and
Machines: Concepts and Perspectives for the Nanoworld, Wiley-VCH,
Weinheim, 2008; (i) Modern Supramolecular Chemistry: Strategies for
Macrocycle Synthesis, ed. F. Diederich, P. Stang and R. R. Tykwinski,
Wiley-VCH, Weinheim, 2008; ( j) J. L. Atwood and J. W. Steed, Supra-
molecular Chemistry, Wiley, 2009; (k) Bottom-up Nanofabrication:
Supramolecules, Self-Assemblies and Organized Films, ed. K. Ariga and
H. S. Nalwa, American Scientific, Valencia/USA, 2009; (l) From Non-
Covalent Assemblies to Molecular Machines, ed. J. P. Sauvage and
P. Gaspard, Wiley-VCH, Weinheim, 2010.
2 For reviews, see: (a) J.-P. Sauvage, Acc. Chem. Res., 1998, 31, 611;
(b) M. Blanco, M. Consuelo Jiménez, J.-C. Chambron, V. Heitz,
M. Linke and J.-P. Sauvage, Chem. Soc. Rev., 1999, 28, 293;
(c) V. Balzani, A. Credi, F. M. Raymo and J. F. Stoddart, Angew. Chem.,
2000, 112, 3484; V. Balzani, A. Credi, F. M. Raymo and J. F. Stoddart,
Angew. Chem., Int. Ed., 2000, 39, 3348; (d) C. A. Schalley, K. Beizai and
F. Vögtle, Acc. Chem. Res., 2001, 34, 465; (e) R. Ballardini, V. Balzani,
A. Credi, M. T. Gandolfi and M. Venturi, Acc. Chem. Res., 2001, 34,
445; (f) A. Harada, Acc. Chem. Res., 2001, 34, 456; (g) J.-P. Collin,
C. Dietrich-Buchecker, P. Gaviña, M. Consuelo Jimenez-Molero and
J.-P. Sauvage, Acc. Chem. Res., 2001, 34, 477; (h) M. Clemente-León,
A. Credi, M.-V. Martínez-Díaz, C. Mingotaud and J. F. Stoddart,
Adv. Mater., 2006, 18, 1291; (i) V. Balzani, A. Credi, S. Silvi and
M. Venturi, Chem. Soc. Rev., 2006, 35, 1135; ( j) A. Credi, Angew.
Chem., Int. Ed., 2007, 119, 5568; A. Credi, Angew. Chem., Int. Ed.,
2007, 46, 5472; (k) D. A. Leigh, F. Zerbetto and E. R. Kay, Angew.
Chem., Int. Ed., 2007, 119, 72; D. A. Leigh, F. Zerbetto and E. R. Kay,
Angew. Chem., Int. Ed., 2007, 46, 72; (l) A. Mateo-Alonso, D. M. Guldi,
F. Paolucci and M. Prato, Angew. Chem., Int. Ed., 2007, 119, 8266;
A. Mateo-Alonso, D. M. Guldi, F. Paolucci and M. Prato, Angew. Chem.,
Int. Ed., 2007, 46, 8120; (m) B. Champin, P. Mobian and J.-P. Sauvage,
Chem. Soc. Rev., 2007, 36, 358; (n) S. Bonnet and J.-P. Collin, Chem.
Soc. Rev., 2008, 37, 1207; (o) S. Silvi, M. Venturi and A. Credi, J. Mater.
Chem., 2009, 19, 2279; (p) P. Bodis, M. R. Panman, B. H. Bakker,
A. Mateo-Alonso, M. Prato, W. J. Buma, A. M. Brouwer, E. R. Kay,
S. A. Leigh and S. Woutersen, Acc. Chem. Res., 2009, 42, 1462;
(q) S. Durot, F. Reviriego and J.-P. Sauvage, Dalton Trans., 2010, 39,
10557.
3 For reviews and selected examples, see: (a) C. O. Dietrich-Buchecker
and J.-P. Sauvage, Chem. Rev., 1987, 87, 795; (b) S. Anderson, H.
L. Anderson and J. K. M. Sanders, Acc. Chem. Res., 1993, 26, 469;
(c) M. J. Blanco, M. C. Jiménez, J. C. Chambron, V. Heitz, M. Linke and
J.-P. Sauvage, Chem. Soc. Rev., 1999, 28, 293; (d) J.-C. Chambron,
J.-P. Collin, V. Heitz, D. Jouvenot, J.-M. Kern, P. Mobian, D. Pomeranc
and J.-P. Sauvage, Eur. J. Org. Chem., 2004, 1627; (e) M. Amman,
P. Bäuerle, A. Rang and C. A. Schalley, Eur. J. Org. Chem., 2006 (8),
1940; (f) M. Hutin, C. A. Schalley, G. Bernardinelli and J. R. Nitschke,
Chem.–Eur. J., 2006, 12, 4069; (g) P. Bäuerle, M. Ammann, M. Wilde,
G. Götz, E. Mena-Osteritz, A. Rang and C. A. Schalley, Angew. Chem.,
Int. Ed., 2007, 119, 367; P. Bäuerle, M. Ammann, M. Wilde, G. Götz,
E. Mena-Osteritz, A. Rang and C. A. Schalley, Angew. Chem., Int. Ed.,
2007, 46, 363; (h) K.-i. Yamashita, M. Kawano and M. Fujita, J. Am.
Chem. Soc., 2007, 129, 1850; (i) C. D. Meyer, C. S. Joiner and
J. F. Stoddart, Chem. Soc. Rev., 2007, 36, 1705; ( j) S. Bonnet and
J.-P. Collin, Chem. Soc. Rev., 2008, 37, 1207; (k) J. D. Crowley,
S. M. Goldup, A.-L. Lee, D. A. Leigh and R. T. McBurney, Chem. Soc.
Rev., 2009, 38, 1530; (l) J. A. Faiz, V. Heitz and J.-P. Sauvage, Chem.
Soc. Rev., 2009, 38, 422; (m) J.-P. Collin, F. Durola, V. Heitz,
F. Reviriego, J.-P. Sauvage and Y. Trolez, Angew. Chem., Int. Ed., 2010,
122, 10370; J.-P. Collin, F. Durola, V. Heitz, F. Reviriego, J.-P. Sauvage
and Y. Trolez, Angew. Chem., Int. Ed., 2010, 49, 10172; (n) G. H. Clever
and M. Shionoya, Chem.–Eur. J., 2010, 16, 11792; (o) J. D. Megiatto, Jr.,
D. I. Schuster, S. Abwandner, G. de Miguel and D. M. Guldi, J. Am.
Chem. Soc., 2010, 132, 3847; (p) K. D. Hänni and D. A. Leigh, Chem.
Soc. Rev., 2010, 39, 1240; (q) G. H. Clever and M. Shionoya, Chem.–
Eur. J., 2010, 16, 11792; (r) J. Guo, P. C. Mayers, G. A. Breault and
C. A. Hunter, Nat. Chem., 2010, 2, 218.
4 For reviews and selected examples, see: (a) D. B. Amabilino and
J. F. Stoddart, Chem. Mater., 1994, 6, 1159; (b) D. Amabilino and
J. F. Stoddart, Chem. Rev., 1995, 95, 2725; (c) P. T. Glink and
J. F. Stoddart, Pure Appl. Chem., 1998, 70, 419; (d) S. A. Nepogodiev
and J. F. Stoddart, Chem. Rev., 1998, 98, 1959; (e) J. W. Lee, S. Samal,
N. Selvapalam, H.-J. Kim and K. Kim, Acc. Chem. Res., 2003, 36, 621;
(f) K. Kim, N. Selvapalam, Y. H. Ko, K. M. Park, D. Kim and J. Kim,
Chem. Soc. Rev., 2007, 36, 267; (g) W. R. Dichtel, O. Š. Miljaniċ,
W. Zhang, J. M. Spruell, K. Patel, I. Aprahamian, J. R. Heath and
J. F. Stoddart, Acc. Chem. Res., 2008, 41, 1750; (h) K. E. Griffiths and
J. F. Stoddart, Pure Appl. Chem., 2008, 80, 485; (i) L. Isaacs, Chem.
Commun., 2009, 619; ( j) E. A. Appel, F. Biedermann, U. Rauwald,
S. T. Jones, J. M. Zayed and O. A. Scherman, J. Am. Chem. Soc., 2010,
132, 14251; (k) M. Zhang, K. Zhu and F. Huang, Chem. Commun., 2010,
46, 8131; (l) H. Y. Au-Yeung, G. D. Pantoş and J. K. M. Sanders, Angew.
Chem., Int. Ed., 2010, 122, 5459; H. Y. Au-Yeung, G. D. Pantoş and
J. K. M. Sanders, Angew. Chem., Int. Ed., 2010, 49, 5331;
(m) F. B. L. Cougnon, H. Y. Au-Yeung, G. D. Pantoş and
J. K. M. Sanders, J. Am. Chem. Soc., 2011, 133, 3198; (n) L. Fang,
S. Basu, C.-H. Sue, A. C. Fahrenbach and J. F. Stoddart, J. Am. Chem.
Soc., 2011, 133, 396; (o) F. Biedermann, U. Rauwald, J. M. Zayed and
O. A. Scherman, Chem. Sci., 2011, 2, 279; (p) Z. Niu, F. Huang and
H. W. Gibson, J. Am. Chem. Soc., 2011, 133, 2836.
5 For reviews and selected examples, see: (a) C. A. Hunter, J. Chem. Soc.,
Chem. Commun., 1991, 749; (b) C. A. Hunter, J. Am. Chem. Soc., 1992,
114, 5305; (c) F. Vögtle, S. Meier and R. Hoss, Angew. Chem., Int. Ed.
Engl., 1992, 104, 1628; F. Vögtle, S. Meier and R. Hoss, Angew. Chem.,
Int. Ed. Engl., 1992, 31, 1619; (d) S. Ottens-Hildebrandt, S. Meier,
W. Schmidt and F. Vögtle, Angew. Chem., Int. Ed. Engl., 1994, 106,
1818; S. Ottens-Hildebrandt, S. Meier, W. Schmidt and F. Vögtle, Angew.
Chem., Int. Ed. Engl., 1994, 33, 1767; (e) F. Vögtle, T. Dünnwald and
T. Schmidt, Acc. Chem. Res., 1996, 29, 451; (f) C. A. Schalley,
T. Weilandt, J. Brüggemann and F. Vögtle, Top. Curr. Chem., 2004, 248,
141; (g) E. R. Kay and D. A. Leigh, Top. Curr. Chem., 2005, 262, 133.
6 For reviews and selected examples, see: (a) K. Kim, Chem. Soc. Rev.,
2002, 31, 96; (b) W. Jiang, H. D. F. Winkler and C. A. Schalley, J. Am.
Chem. Soc., 2008, 130, 13852; (c) W. Jiang and C. A. Schalley, Proc.
Natl. Acad. Sci. U. S. A., 2009, 106, 10425; (d) J. F. Stoddart, Chem. Soc.
Rev., 2009, 38, 1802; (e) C.-F. Leel, D. A. Leigh, R. G. Pritchard,
D. Schultz, S. J. Teat, G. A. Timco and R. E. P. Winpenny, Nature, 2009,
458, 314; (f) W. Jiang, P. C. Mohr, A. Schäfer and C. A. Schalley, J. Am.
Chem. Soc., 2010, 132, 2309; (g) W. Jiang and C. A. Schalley, Beilstein
J. Org. Chem., 2010, 6(14); (h) L. Fang, M. A. Olson, D. Benítez,
E. Tkatchouk, W. A. Goddard III and J. F. Stoddart, Chem. Soc. Rev.,
2010, 39, 17; (i) X. Ma and H. Tian, Chem. Soc. Rev., 2010, 39, 70.
7 For reviews and selected examples, see: (a) G. M. Hübner, J. Gläser,
C. Seel and F. Vögtle, Angew. Chem., 1999, 111, 395; G. M. Hübner,
J. Gläser, C. Seel and F. Vögtle, Angew. Chem., Int. Ed., 1999, 38, 282;
(b) C. A. Schalley, G. Silva, C.-F. Nising and P. Linnartz, Helv. Chim.
Acta, 2002, 85, 1578; (c) P. Ghosh, O. Mermagen and C. A. Schalley,
Chem. Commun., 2002, 2628; (d) P. D. Beer, M. R. Sambrook and
D. Curiel, Chem. Commun., 2006, 2105; (e) M. S. Vickers and
P. D. Beer, Chem. Soc. Rev., 2007, 36, 211; (f) M. D. Lankshear and
P. D. Beer, Acc. Chem. Res., 2007, 40, 657; (g) K. M. Mullen and
P. D. Beer, Chem. Soc. Rev., 2009, 38, 1701; (h) M. J. Chmielewski,
J. J. Davis and P. D. Beer, Org. Biomol. Chem., 2009, 7, 415;
(i) H.-Y. Gong, B. M. Rambo, E. Karnas, V. M. Lynch and J. L. Sessler,
Nat. Chem., 2010, 2, 406; ( j) C. J. Serpell, J. Cookson, A. L. Thompson
and P. D. Beer, Chem. Sci., 2011, 2, 494; (k) N. H. Evans, C. J. Serpell
and P. D. Beer, Angew. Chem., Int. Ed., 2011, 123, 2555; N. H. Evans,
C. J. Serpell and P. D. Beer, Angew. Chem., Int. Ed., 2011, 50, 2507;
(l) T. B. Gasa, C. Valente and J. F. Stoddart, Chem. Soc. Rev., 2011, 40, 57.
8 For reviews and selected examples, see: (a) J. D. Badjiċ, A. Nelson,
S. J. Cantrill, W. B. Turnbull and J. F. Stoddart, Acc. Chem. Res., 2005,
38, 723; (b) W. Jiang, M. Han, H.-Y. Zhang, Z.-J. Zhang and Y. Liu,
Chem.–Eur. J., 2009, 15, 9938; (c) B. Baytekin, S. S. Zhu,
B. Brusilowskij, J. Illigen, J. Ranta, J. Huuskonen, L. Russo,
K. Rissanen, L. Kaufmann and C. A. Schalley, Chem.–Eur. J., 2008, 14,
10012; (d) C.-F. Chen, Chem. Commun., 2011, 47, 1674.
9 For reviews and selected examples, see: (a) M. Mammen, S.-K. Choi
and G. M. Whitesides, Angew. Chem., Int. Ed., 1998, 37, 2754;
(b) A. Mulder, J. Huskens and D. N. Reinhoudt, Org. Biomol. Chem.,
2004, 2, 3409; (c) L. L. Kiessling, J. E. Gestwicki and L. E. Strong,
Angew. Chem., Int. Ed., 2006, 118, 2408; L. L. Kiessling, J. E. Gestwicki
and L. E. Strong, Angew. Chem., Int. Ed., 2006, 45, 2348;
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 5954–5964 | 5963

View Online
(45) J. J. Reczek, A. A. Kennedy, B. T. Halbert and A. R. Urbach, J. Am.
Chem. Soc., 2009, 131, 2408.
Commun., 1996, 1361; (c) H. Adams, F. J. Carver, C. A. Hunter and
N. J. Osborne, Chem. Commun., 1996, 2529; (d) C. Allot, H. Adams,
P. L. Bernard, Jr., C. A. Hunter, C. Rotger and J. A. Thomas, Chem.
Commun., 1998, 2449.
10 For reviews and selected examples, see: (a) J. R. Johnson, N. Fu,
E. Arunkumar, W. M. Leevy, S. T. Gammon, D. Piwnica-Worms and
B. D. Smith, Angew. Chem., Int. Ed., 2007, 119, 5624; J. R. Johnson,
N. Fu, E. Arunkumar, W. M. Leevy, S. T. Gammon, D. Piwnica-Worms
and B. D. Smith, Angew. Chem., Int. Ed., 2007, 46, 5528;
(b) J. J. Gassensmith, E. Arunkumar, L. Barr, J. M. Baumes,
K. M. DiVittorio, J. R. Johnson, B. C. Noll and B. D. Smith, J. Am.
Chem. Soc., 2007, 129, 15054; (c) J. J. Gassensmith, J. M. Baumes and
B. D. Smith, Chem. Commun., 2009, 6329; (d) J. M. Baumes,
J. J. Gassensmith, J. Giblin, J.-J. Lee, A. G. White, W. J. Culligan,
W. M. Leevy, M. Kuno and B. D. Smith, Nat. Chem., 2010, 2, 1025.
11 (a) U. Herrmann, T. Jonischkeit, J. Bargon, U. Hahn, Q.-Y. Li,
C. A. Schalley, E. Vogel and F. Vögtle, Anal. Bioanal. Chem., 2002, 372,
611; (b) J. Bargon, S. Braschoß, J. Flörke, U. Herrmann, L. Klein,
J. W. Lörgen, M. Lopez, S. Maric, A. H. Parham, P. Piacenza,
H. Schäfgen, C. A. Schalley, G. Silva, H. Schwierz, F. Vögtle and
G. Windscheif, Sens. Actuators, B, 2003, 95, 6; (c) G. Kleefisch,
C. Kreutz, J. Bargon, G. Silva and C. A. Schalley, Sensors, 2004, 4, 136.
12 (a) M. Sokolowski, I. Kossev, W. Reckien, T. Felder, M. R. Kishan and
C. A. Schalley, J. Phys. Chem. C, 2009, 113, 12870; (b) I. Kossev,
W. Reckien, B. Kirchner, T. Felder, M. Nieger, C. A. Schalley, F. Vögtle
and M. Sokolowski, Adv. Funct. Mater., 2007, 17, 513; (c) I. Kossev,
T. Felder, C. A. Schalley, F. Vögtle and M. Sokolowski, Springer Proc.
Phys., 2009, 127, 235.
24 (a) W. Reckien and S. Peyerimhoff, J. Phys. Chem. A, 2003, 107, 9634;
(b) C. A. Schalley, W. Reckien, S. Peyerimhoff, B. Baytekin and
F. Vögtle, Chem.–Eur. J., 2004, 10, 4777; (c) S. S. Zhu, M. Nieger,
J. Daniels, T. Felder, I. Kossev, T. Schmidt, M. Sokolowski, F. Vögtle
and C. A. Schalley, Chem.–Eur. J., 2009, 15, 5040.
25 (a) P. Ghosh, G. Federwisch, M. Kogej, C. A. Schalley, D. Haase,
W. Saak, A. Lützen and R. M. Gschwind, Org. Biomol. Chem., 2005, 3,
2691; (b) E. V. Dzyuba, L. Kaufmann, N. L. Löw, A. K. Meyer,
H. D. F. Winkler, K. Rissanen and C. A. Schalley, Org. Lett., 2011, 13,
4838.
26 Also, see: N. L. Löw, E. V. Dzyuba, B. Brusilowskij, L. Kaufmann,
E. Franzmann, W. Maison, E. Brandt, D. Aicher, A. Wiehe and
C. A. Schalley, Beilstein J. Org. Chem., 2012, 8, 234–245.
27 (a) S. Ottens-Hildebrandt, M. Nieger, K. Rissanen, J. Rouvinen,
S. Meier, G. Harder and F. Vögtle, J. Chem. Soc., Chem. Commun.,
1995, 777; (b) C. Reuter, C. Seel, M. Nieger and F. Vögtle, Helv. Chim.
Acta, 2000, 83, 630; (c) A. Mohry, F. Vögtle, M. Nieger and H. Hupfer,
Chirality, 2000, 12, 76.
28 X.-Y. Li, J. Illigen, M. Nieger, S. Michel and C. A. Schalley, Chem.–Eur.
J., 2003, 9, 1332.
29 K. Hirose, Determination of binding constants, in Analytical Methods in
Supramolecular Chemistry, ed. C. A. Schalley, Wiley-VCH, Weinheim,
2007, pp. 17–54.
30 (a) F. Schmidtchen, Isothermal titration calorimetry in supramolecular
chemistry, in Analytical Methods in Supramolecular Chemistry,
ed. C. A. Schalley, Wiley-VCH, Weinheim, 2006, pp. 55–78;
(b) G. A. Holdgate, BioTechniques, 2001, 31, 164.
31 T. Wiseman, S. Williston, J. F. Brandts and L.-N. Lin, Anal. Biochem.,
1989, 179, 131.
13 (a) A. Affeld, G. M. Hübner, C. Seel and C. A. Schalley, Eur. J. Org.
Chem., 2001, 2877; (b) P. Linnartz, S. Bitter and C. A. Schalley,
Eur. J. Org. Chem., 2003, 4819; (c) T. Felder and C. A. Schalley, Angew.
Chem., Int. Ed., 2003, 115, 2360; T. Felder and C. A. Schalley, Angew.
Chem., Int. Ed., 2003, 42, 2258; (d) P. Linnartz and C. A. Schalley,
Supramol. Chem., 2004, 16, 263.
14 S.-Y. Chang, H. S. Kim, K.-J. Chang and K.-S. Jeong, Org. Lett., 2004,
6, 181.
32 W. B. Turnbull and A. H. Daranas, J. Am. Chem. Soc., 2003, 125, 14859.
33 (a) J. M. Kang and J. Rebek, Jr., Nature, 1996, 382, 239; (b) T. N. Parac,
D. L. Caulder and K. N. Raymond, J. Am. Chem. Soc., 1998, 120, 8003;
(c) A. Hosseini, S. Taylor, G. Accorsi, N. Armaroli, C. A. Reed and
P. D. W. Boyd, J. Am. Chem. Soc., 2006, 128, 15903; (d) K. N. Houk,
A. G. Leach, S. P. Kim and X. Zhang, Angew. Chem., Int. Ed., 2003, 115,
5020; K. N. Houk, A. G. Leach, S. P. Kim and X. Zhang, Angew. Chem.,
Int. Ed., 2003, 42, 4872.
15 (a) W. L. Jorgensen and J. Pranata, J. Am. Chem. Soc., 1990, 112, 2008;
(b) K.-S. Jeong, T. Tjivikua and J. Rebek, Jr., J. Am. Chem. Soc., 1990,
112, 3215; (c) J. Pranata, S. G. Wierschke and W. L. Jorgensen, J. Am.
Chem. Soc., 1991, 113, 2810; (d) J. T. Murray and S. C. Zimmermann,
J. Am. Chem. Soc., 1992, 114, 4010.
16 C. Spickermann, T. Felder, C. A. Schalley and B. Kirchner, Chem.–Eur.
J., 2008, 14, 1216.
17 B. Kirchner, C. Spickermann, W. Reckien and C. A. Schalley, J. Am.
Chem. Soc., 2010, 132, 484.
34 R. W. Hooft, COLLECT, Nonius BV, Delft, The Netherlands, 1998.
35 Z. Otwinowski and W. Minor, Methods Enzymol. Macromolecular Crys-
tallography, Part A, 1997, 276, 307.
36 L. Palatinus and G. Chapuis, J. Appl. Crystallogr., 2007, 40, 786.
37 L. J. Farrugia, J. Appl. Crystallogr., 1999, 32, 837.
38 G. M. Sheldrick, SHELXL-97 – A Program for the Refinement of Crystal
Structures, University of Göttingen, Germany, 1997, release 97–2.
39 G. M. Sheldrick, SADABS, Version 2008/2, Universität Göttingen, Göt-
tingen, Germany, 2008.
40 K. Eichkorn, O. Treutler, H. Öhm, M. Häser and R. Ahlrichs, Chem.
Phys. Lett., 1995, 240, 283.
41 (a) A. Schäfer, C. Huber and R. Ahlrichs, J. Chem. Phys., 1994, 100,
5829; (b) S. J. Grimme, Comput. Chem., 2004, 25, 1463;
(c) S. J. Grimme, Comput. Chem., 2006, 27, 1787.
42 R. Ahlrichs, M. Bär, M. Häser, H. Horn and C. Kölmel, Chem. Phys.
Lett., 1989, 162, 165. For the current version, see: http://www.turbomole.
de.
18 (a) A. G. Johnson, D. A. Leigh, R. J. Pritchard, J. P. Smart and
M. D. Deegan, Angew. Chem., Int. Ed. Engl., 1995, 107, 1324; A.
G. Johnson, D. A. Leigh, R. J. Pritchard, J. P. Smart and M. D. Deegan,
Angew. Chem., Int. Ed. Engl., 1995, 34, 1209; (b) A. G. Johnson,
D. A. Leigh, L. Nezhat, J. P. Smart and M. D. Deegan, Angew. Chem.,
Int. Ed. Engl., 1995, 107, 1327; A. G. Johnson, D. A. Leigh, L. Nezhat,
J. P. Smart and M. D. Deegan, Angew. Chem., Int. Ed. Engl., 1995, 34,
1212.
19 For Hammett substituent constants, see: C. Hansch, A. Leo and R.
W. Taft, Chem. Rev., 1991, 91, 165.
20 (a) J. L. Sessler, D. E. Gross, W.-S. Cho, V. M. Lynch, F. P. Schmidtchen,
G. W. Bates, M. E. Light and P. A. Gale, J. Am. Chem. Soc., 2006, 128,
12281; (b) D. E. Gross, F. P. Schmidtchen, W. Antonius, P. A. Gale,
V. M. Lynch and J. L. Sessler, Chem.–Eur. J., 2008, 14, 7822.
21 For another recent example of the benefits of the combination of both
methods, see: J. Hornung, D. Fankhauser, L. D. Shirtcliff, A. Praetorius,
W. B. Schweizer and F. Diederich, Chem.–Eur. J., 2011, 17, 12362.
22 O. Braun, A. Hünten and F. Vögtle, J. Prakt. Chem., 1999, 341, 542.
23 (a) F. J. Carver, C. A. Hunter and R. J. Shannon, J. Chem. Soc., Chem.
Commun., 1994, 1277; (b) C. A. Hunter and R. J. Shannon, Chem.
43 S. Boys and F. Bernardi, Mol. Phys., 1970, 19, 553.
44 E. R. Davidson, J. Chem. Phys., 1967, 46, 3320.
45 (a) J. Thar and B. Kirchner, J. Phys. Chem. A, 2006, 110, 4229;
(b) K. Wendler, J. Thar, S. Zahn and B. Kirchner, J. Phys. Chem. A,
2010, 114, 9529.
5964 | Org. Biomol. Chem., 2012, 10, 5954–5964
This journal is © The Royal Society of Chemistry 2012