Structure-reactivity relationship in interlocked molecular compounds and in their supramolecular model complexes

Article abstract of DOI:10.1021/ja962937z

Examination of the pseudorotaxane-like geometries adopted in the solid state by a series of 1:1 complexes revealed significant differences in the hydrogen bonding interactions between oxygen atoms in some hydroquinone-based guests carrying polyether/polye

Full text of DOI:10.1021/ja962937z

2614
J. Am. Chem. Soc. 1997, 119, 2614-2627
Structure-Reactivity Relationship in Interlocked Molecular
Compounds and in Their Supramolecular Model Complexes†
Masumi Asakawa,‡ Christopher L. Brown,‡ Stephan Menzer,§
Franc¸isco M. Raymo,‡ J. Fraser Stoddart,*,‡ and David J. Williams§
Contribution from the School of Chemistry, UniVersity of Birmingham,
Edgbaston, Birmingham B15 2TT, U.K., and Department of Chemistry,
Imperial College, South Kensington, London SW7 2AY, U.K.
ReceiVed August 21, 1996X
Abstract: Examination of the pseudorotaxane-like geometries adopted in the solid state by a series of 1:1 complexes
revealed significant differences in the hydrogen bonding interactions between oxygen atoms in some hydroquinone-
based guests carrying polyether/polyester functions and the acidic hydrogen atoms on the bipyridinium units of the
hostscyclobis(paraquat-p-phenylene). These differences are reflected directly in the stabilities of the complexes in
solution and dramatic changes in the magnitudes of their association constants (Ka values ranging from 130 to 4300
M-1 in MeCN at 25 °C) are observed upon varying the location of the carbonyl ester function(s) along the polyether/
ester chains. A similar effect (Ka values ranging from 5 to 730 M-1 in Me2CO at 25 °C) was observed in the
binding of paraquat as its bipyridinium bis(hexafluorophosphate) salt by analogous macrocyclic hydroquinone-based
mono- and bis-lactones. Investigations of the kinetics of hydrolyses of the ester functions revealed thatswhile inert
in their free formssthe macrocyclic mono- and bis-lactones undergo hydrolysis when incorporated within [2]catenanes
composed of one of these macrocyclic lactones and cyclobis(paraquat-p-phenylene). Presumably, the enhanced
reactivity of the ester functions is a result of [C-H‚‚‚O] hydrogen bonding interactions involving the ester carbonyl
oxygen atoms and the acidic hydrogen atoms on the bipyridinium units, as suggested by single-crystal X-ray
crystallographic analyses. Thus, cyclobis(paraquat-p-phenylene) can act as a mechanically-interlocked “catalyst”.
Introduction
functionalities along their polyether substituents have been
investigated.4 However, the presence of ester functions within
the polyether chains has a significant depressive effect on the
stability of the corresponding complexes. Intrigued as we were
by these observations, we envisaged the possibility of synthesiz-
ing a number of hydroquinone-based acyclic and macrocyclic
polyether/ester compounds in which the position of the ester
functions was varied systematically. Once prepared, we argued
that these model compounds would provide us with the
opportunity to investigate the effect of subtle structural changes
upon (i) the efficiencies of the related self-assembly processes,
(ii) the geometries in the solid and solution states, and (iii) the
reactivites of the resulting molecular assemblies and supra-
molecular arrays. In this paper, we relate how we afforded
ourselves these opportunities.
In recent research,1 we have employed the tetracationic
cyclophane cyclobis(paraquat-p-phenylene) to self-assemble2
catenanes, rotaxanes, and pseudorotaxanes3 incorporating hy-
droquinone-based polyether components. In particular, the
complexes formed involving cyclobis(paraquat-p-phenylene) and
paraquat bis(hexafluorophosphate) with acyclic and macrocyclic,
respectively, hydroquinone-based compounds incorporating ester
† Molecular Meccano. 15. For part 14, see: Ashton, P. R.; Ballardini,
R.; Balzani, V.; Boyd, S. E.; Credi, A.; Gandolfi, M. T.; Go´mez-Lo´pez,
M.; Iqbal, S.; Philp, D.; Preece, J. A.; Prodi, L.; Ricketts, H. G.; Stoddart,
J. F.; Tolley, M. S.; Venturi, M.; White, A. J. P.; Williams, D. J. Chem.
Eur. J. 1997, 3, 146-164.
‡ University of Birmingham.
§ Imperial College.
X Abstract published in AdVance ACS Abstracts, February 15, 1997.
(1) (a) Philp, D.; Stoddart, J. F. Synlett 1991, 445-458. (b) Amabilino,
D. B.; Stoddart, J. F. Pure Appl. Chem. 1993, 65, 2351-2359. (c) Pasini,
D.; Raymo, F. M.; Stoddart, J. F. Gazz. Chim. It. 1995, 125, 431-443. (d)
Beˇlohradsky´, M.; Philp, D.; Raymo, F. M.; Stoddart J. F. in Organic
ReactiVity: Physical and Biological Aspects; Golding, B. T., Griffin, R. J.,
Maskill, H., Eds.; RSC Special Publication No. 148; Cambridge, U.K., 1995;
pp 387-398. (e) Amabilino, D. B.; Raymo, F. M.; Stoddart, J. F. In
ComprehensiVe Supramolecular Chemistry; Sauvage, J.-P., Hosseini, M.
W., Eds.; Pergamon: Oxford, U.K., 1996; Vol. 9, pp 85-130.
(2) (a) Lindsey, J. S. New J. Chem. 1991, 15, 153-180. (b) Whitesides,
G. M.; Mathias, J. P.; Seto, C. T. Science 1991, 254, 1312-1319. (c)
Lawrence, D. S.; Jiang, T.; Levett, M. Chem. ReV. 1995, 95, 2229-2260.
(d) Raymo, F. M.; Stoddart, J. F. Curr. Opin. Colloid Interface Sci. 1996,
1, 116-126. (e) Philp, D.; Stoddart J. F. Angew. Chem., Int. Ed. Engl. 1996,
35, 1154-1196.
Results and Discussion
Synthesis.5 A series of π-electron-rich hydroquinone-based
acyclic compounds incorporating one carbonyl group within one
or both of their two polyether chains were synthesized as shown
in Schemes 1 and 2. Esterification of MEEHB with 2-(2-
methoxyethoxy)acetyl chloride afforded (Scheme 1a) RCB-
MEEB. Alkylation of MEEHB with 2-chloroethanol produced
(Scheme 1b) MEEHEB, which was reacted with 2-methoxy-
acetyl chloride to give γCBMEEB. The compounds BRCMEEB
and BγCMEEB were synthesized (Scheme 2, parts a and b,
respectively) by esterification of 1/4DHB with 2-(2-methoxy-
ethoxy)acetyl chloride and of BHEB with 2-methoxyacetyl
chloride, respectively. The methyl esters BδCMEEB,
BúCMEEEB, and BθCMEEEEB were prepared (Scheme 2c)
by transesterification of the corresponding tert-butyl esters.
The macrocyclic bis-lactone BδCPP34C10 was synthesized
(Scheme 3) by reacting the bisacid chloride of BδCHEEB with
(3) (a) Dietrich-Buchecker, C. O.; Sauvage J.-P. Bioorg. Chem. Front.
1991, 2, 195-248. (b) Gibson, H. W.; Marand, H. AdV. Mater. 1993, 5,
11-21. (c) Chambron, J. C.; Dietrich-Buchecker, C. O.; Sauvage, J.-P. Top.
Curr. Chem. 1993, 165, 131-162. (d) Gibson, H. W.; Bheda, M. C.; Engen.,
P. T. Prog. Polym. Sci. 1994, 19, 843-945. (e) Amabilino, D. B.; Parson,
I. W.; Stoddart, J. F. Trends Polym. Sci. 1994, 2, 146-152. (f) Amabilino,
D. B.; Stoddart, J. F. Chem. ReV. 1995, 95, 2725-2828. (g) Beˇlohradsky´,
M.; Raymo, F. M.; Stoddart, J. F. Collect. Czech. Chem. Commun. 1996,
61, 1-43. (h) Raymo, F. M.; Stoddart, J. F. Trends Polym. Sci. 1996, 4,
208-211.
(4) Asakawa, M.; Ashton, P. R.; Menzer, S.; Raymo, F. M.; Stoddart, J.
F.; White, A. J. P.; Williams, D. J. Chem. Eur. J. 1996, 2, 877-893.
S0002-7863(96)02937-X CCC: $14.00 © 1997 American Chemical Society

Interlocked Molecular Compounds
J. Am. Chem. Soc., Vol. 119, No. 11, 1997 2615
Scheme 1
Scheme 3
Scheme 4
Scheme 2
BBB in the presence of the macrocyclic bislactone BδCPP34C10
afforded the [2]catenane 4‚4PF6, after counterion exchange.
X-ray Crystallography. The supramolecular geometries
(Figures 1-5), in the solid state, of the [2]pseudorotaxanes listed
in Table 1 have been deduced by single-crystal X-ray analyses.
In all instances, the π-electron-rich hydroquinone ring is
positioned centrally within the tetracationic cyclophane (all the
superstructures have Ci symmetry) with its OC6H4O axis
inclined by angles of tilt rangingswith one exceptionsbetween
46 and 56°. The exception is {[BRCMEEB]-[BBIPYBIXY-
CY]}4+ (Figure 2), a diphenolic diester, where the tilt angle is
significantly larger at 69° and the torsional angle about the aryl
carbon-oxygen bond is 70°. In addition to the normal face-
to-face and T-type edge-to-face stabilizing interactions involving
aromatic units, there are hydrogen bonds formed between the
hydrogen atoms (HR) in the R-positions with respect to the
nitrogen atoms on the bipyridinium units and the second and
third oxygen atoms Ob and Oc, respectively, along the polyether/
ester chains, except when the carbonyl groups are located in
BHEEB under high-dilution conditions. Reaction (Scheme 4)
of the bis(hexafluorophosphate) salt [BPYPYXY][PF6]2 with
(5) It is convenient at this point to describe the acronyms, composed of
letters and numbers, used throughout the text and in the illustrations that
appear in the figures and schemes. 1,4-Dihydroxybenzene, 1,4-bis(bro-
momethyl)benzene, and bis(p-phenylene)-34-crown-10 are abbreviated to
1/4DHB, BBB, and BPP34C10, respectively. The salt, 1,1′-dimethyl-4,4′-
bipyridinium hexafluorophosphatescommonly known as paraquatsis ab-
breviated to [PQT][PF6]2. The other acronyms can be deduced by applying
the following rules. B stands for benzene when present at the end of a
name and for bis when present in other parts of the name. tBu, C, E, H, M,
and P stand for tert-butoxy, carbonyl, ethoxy, hydroxy, methoxy, and
phenoxy groups, respectively. CY, XY, BIXY, BIPY, and PYPY stand for
cyclophane, xylylene, bis(xylylene), bipyridinium, and pyridylpyridinium
units, respectively. The position of the carbonyl groups in the polyether
chains is indicated by a Greek letter, starting from the carbon atom directly
attached to the hydroquinone ring and proceeding away from it in a stepwise
fashion. Numbers (i.e., 1‚4PF6, 2‚4PF6, 3‚4PF6, and 4‚4PF6, respectively)
are employed to indicate the [2]catenanes {[2]-[BPP34C10]-[BBIPY-
BIXYCY]-catenane}[PF6]4, {[2]-[âCBPP34C10]-[BBIPYBIXYCY]catenane}-
[PF6]4, {[2]-[BâCPP34C10]-[BBIPYBIXYCY]catenane}[PF6]4, and {[2]-
[BδCPP34C10]-[BBIPYBIXYCY]catenane}[PF6]4.
Figure 1. X-ray crystal structure of the [2]pseudorotaxane {[BMEEB]-
[BBIPYBIXYCY]}4+ showing the [C-H‚‚‚O] hydrogen bonding
interactions.

2616 J. Am. Chem. Soc., Vol. 119, No. 11, 1997
Asakawa et al.
Figure 5. X-ray crystal structure of the [2]pseudorotaxane
{[BθCMEEEEB]-[BBIPYBIXYCY]}4+ showing the [C-H‚‚‚O] hy-
drogen bonding interactions.
the [O-CO-CH2-O] linkages. As previously observed4 for
the [2]pseudorotaxane {[BâCMEEB]-[BBIPYBIXYCY]}4+, in
the case of BγCMEEB and BθCMEEEEB, the carbonyl oxygen
atoms of symmetry-related complexes form pairs of inter-
complex hydrogen bonds with the hydrogen atoms HR and Hâ,
respectively.
Figure 2. X-ray crystal structure of the [2]pseudorotaxane
{[BRCMEEB]-[BBIPYBIXYCY]}4+
.
Despite the potential for two translational isomers, both of
which are observed4 in solution (Vide infra), the single-crystal
X-ray analyses of the [2]catenanes 34+ (Figure 6) and 44+
(Figure 7) revealed only the translational isomers in which the
ester groups are positioned proximal to the hydroquinone ring
located inside the cavity of the tetracationic cyclophane
component. In 34+ and in both crystallographically-independent
molecules of 44+, the mode of interlocking is very similar (Table
2) to that observed7 in 14+, although, in 44+, the inside
hydroquinone ring is displaced significantly toward the alongside
bipyridinium unit, cf. a symmmetrical positioning in the other
two [2]catenanes. In addition, in 34+ and 44+, the inside
hydroquinone rings are displaced toward one of the p-xylyl
spacers of the tetracationic cyclophane components, producing
a noticeable shortening in the associated [CH‚‚‚π] interactions.
The OC6H4O axes of the inside hydroquinone rings are inclined
by ca. 53° in 34+ and by ca. 45 and 48° in the two
crystallographically-independent molecules of 44+ to the plane
of the tetracationic cyclophane components. These tilt angles
τi are very similar to those observed (Table 1) in the case of
the related [2]pseudorotaxanes {[BâCMEEB]-[BBIPYBIXY-
CY]}4+ and {[BδCMEEB]-[BBIPYBIXYCY]}4+. In 34+, the
OC6H4O axis of the alongside hydroquinone ring has an
appreciably smaller tilt angle τa to the plane of the tetracationic
cyclophane component than those observed in 44+, presumably
as a consequence of the differencies in the [C-H‚‚‚O] hydrogen
bonding interactions between the hydrogen atoms HR and the
polyether/ester oxygen atoms. In contrast with 44+, where one
of the ester carbonyl oxygen atoms is directed toward an HR
hydrogen atom, in 34+, both ester carbonyl groups are directed
away from the plane of the tetracationic cyclophane component
and are not involved in any intra-catenane hydrogen bonding
interactions. However, in 34+, there are hydrogen bonding
interactions between one of the HR hydrogen atoms and the third
Figure 3. X-ray crystal structure of the [2]pseudorotaxane
{[BγCMEEB]-[BBIPYBIXYCY]}4+ showing the [C-H‚‚‚O] hydrogen
bonding interactions.
Figure 4. X-ray crystal structure of the [2]pseudorotaxane
{[BδCMEEB]-[BBIPYBIXYCY]}4+ showing the [C-H‚‚‚O] hydrogen
bonding interactions.
(6) With the exception of {[BRCMEEB]-[BBIPYBIXYCY]}4+ and
{[BδCMEEB]-[BBIPYBIXYCY]}4+, the oxygen atoms of the carbonyl
groups are involved in hydrogen bonding interactions with the hydrogen
atoms HR or Hâ in the R- or â-positions, respectively, with respect to the
nitrogen atoms on the bipyridinium units of the adjacent symmetry-related
or lattice-related complexes. In {[BRCMEEB]-[BBIPYBIXYCY]}4+, each
carbonyl oxygen atom gives rise to intra-pseudorotaxane hydrogen bonding
interactions with the two hydrogen atoms Hâ of the adjacent bipyridinium
unit. These interactions are responsible for the higher tilt angle τ observed
in this pseudorotaxane. In {[BδCMEEB]-[BBIPYBIXYCY]}4+, the carbonyl
oxygen atoms sustain intra-pseudorotaxane hydrogen bonding interactions
with the hydrogen atoms HR.
(7) Anelli, P. L.; Ashton, P. R.; Ballardini, R.; Balzani, V.; Delgado,
M.; Gandolfi, M. T.; Goodnow, T. T.; Kaifer, A. E.; Philp, D.; Pietraszk-
iewicz, M.; Prodi, L.; Reddington, M. V.; Slawin, A. M. Z.; Spencer, N.;
Stoddart, J. F.; Vicent, C.; Williams, D. J. J. Am. Chem. Soc. 1992, 114,
193-218.
the R-positions. In {[BâCMEEB]-[BBIPYBIXYCY]}4+ and
{[BγCMEEB]-[BBIPYBIXYCY]}4+ (Figure 3),4 it is the oxy-
gen atom Oc that is involved in the shortest hydrogen bonding
interaction with HR, whereas in the other pseudorotaxanes, it is
Ob. In {[BRCMEEB]-[BBIPYBIXYCY]}4+, neither Ob nor Oc
are involved in hydrogen bonding.6 When the carbonyl groups
in the [2]pseudorotaxanes listed in Table 1 are located in either
the â- or γ-positions (Figure 3) along the polyether/ester chains,
the [O-CO-CH2-O] linkages adopt syn-periplanar conforma-
tions in order to sustain hydrogen bonding interactions between
Oc and HR. When the carbonyl groups are moved to the R-,
δ-, and θ-positions (Figures 2, 4, and 5, respectively), the more
stable (Vide infra) anti-periplanar conformation is adopted by

Interlocked Molecular Compounds
J. Am. Chem. Soc., Vol. 119, No. 11, 1997 2617
Table 1. Distancesa (Å) and Anglesa (deg) Characterizing the Molecular and Supramolecular Geometries of the Cyclophane
{[BBIPYBIXYCY]}4+, and the [2]Pseudorotaxanes {[BMEEB]-[BBIPYBIXYCY]}4+, {[B(R-δ)CMEEB]-[BBIPYBIXYCY]}4+ and
{[BθCMEEEEB]-[BBIPYBIXYCY]}4+
compound
θ
ψ
τ
Oa‚‚‚N Ob‚‚‚N Oc‚‚‚N CR‚‚‚Od HR‚‚‚Od CRHROd Z‚‚‚Z′ Y‚‚‚Y′ H‚‚‚Y XHY
{[BBIPYBIXYCY]}4+ b
19 23
16 27 49 4.12
14 30 69 5.38
6.82 10.31
{[BMEEB]-[BBIPYBIXYCY]}4+
{[BRCMEEB]-[BBIPYBIXYCY]}4+
{[BâCMEEB]-[BBIPYBIXYCY]}4+ c
{[BγCMEEB]-[BBIPYBIXYCY]}4+
{[BδCMEEB]-[BBIPYBIXYCY]}4+
4.26
7.01
4.72
4.51
4.31
4.35
3.89 3.15 (Ob) 2.34 (Ob) 141 (Ob) 7.09 10.18 2.81
8.67 7.24 10.12 2.87
3.91 3.19 (Oc) 2.25 (Oc) 165 (Oc) 7.08 10.22 2.79
3.95 3.23 (Oc) 2.34 (Oc) 153 (Oc) 7.10 10.25 2.88
3.86f 3.30 (Ob) 2.50 (Ob) 141 (Ob) 7.05 10.21 2.82
4.12 3.32 (Ob) 2.53 (Ob) 143 (Ob) 7.07 10.26 2.88
165
152
173
159
162
160
e
e
e
7
26 56 4.33
17 27 46 4.03
17 26 47 3.97
{[BθCMEEEEB]-[BBIPYBIXYCY]}4+ 16 26 46 3.99
a The distances and angles indicated in the table are illustrated in the diagrams A, B, and C:
b The X-ray crystal structure of {[BBIPYBIXYCY]}4+ has been reported previously in the literature (Anelli, P. L.; Ashton, P. R.; Ballardini, R.;
Balzani, V.; Delgado, M.; Gandolfi, M. T.; Goodnow, T. T.; Kaifer, A. E.; Philp, D.; Pietraszkiewicz, M.; Prodi, L.; Reddington, M. V.; Slawin,
A. M. Z.; Spencer, N.; Stoddart, J. F.; Vincent, C.; Williams, D. J. J. Am. Chem. Soc. 1992, 114, 193-218). c The X-ray crystal structure of
{[BâCMEEB]-[BBIPYBIXYCY]}4+ has been reported previously in the literature (Asakawa, M.; Ashton, P. R.; Menzer, S.; Raymo, F. M.; Stoddart,
J. F.; White, A. J. P.; Williams, D. J. Chem. Eur. J. 1996, 2, 877-893). d The polyether oxygen atoms involved in the shortest hydrogen bonding
interactions with the HR protons are given in parentheses for each [2]pseudorotaxane. e In the case of {[BRCMEEB]-[BBIPYBIXYCY]}4+, the
hydrogen atoms HR are not involved in hydrogen bonding interactions. f In the case of {[BδCMEEB]-[BBIPYBIXYCY]}4+, the oxygen atoms Oc
are the carbonyl oxygen atoms and are involved in hydrogen bonding interactions (lengths [CR‚‚‚O] and [HR‚‚‚O], and angle [CRHRO], 3.33 and
2.56 Å, and 152°, respectively) with the hydrogen atoms HR.
the conformation of the two polyether/ester linkages. Nonethe-
less, in both molecules, only one of the two ester carbonyl
oxygen atoms is oriented inward, facilitating hydrogen bonding
with one of the HR hydrogen atoms, while the other is directed
away from any hydrogen bond donors within the [2]catenane.
A consequence of the conformational differences in the poly-
ether/ester linkage is a marked change in the relative orientations
of the OC6H4O axes of the alongside hydroquinone rings with
respect to their inside counterparts. In addition to the afore-
mentioned hydrogen bonds to one of the ester carbonyl oxygen
atoms, there are [C-H‚‚‚O] hydrogen bonds from the dia-
metrically opposite HR hydrogen atom to the second oxygen
atom (counted from the inside hydroquinone ring) of the
polyether/ester linkage containing the outwardly-directed car-
bonyl group. These two different types of hydrogen bonding
almost certainly contribute to the large twist θi (ca. 25°) between
Figure 6. X-ray crystal structure of the [2]catenane 34+ showing the
the two pyridinium rings of the inside bipyridinium units, cf.
[C-H‚‚‚O] hydrogen bonding interactions.
13° in 34+. Both crystallographically independent molecules
form conventional polar donor-acceptor stacks with interstack
[C-H‚‚‚O] hydrogen bonds involving the outwardly-directed
carbonyl groups.
(counting from the inside hydroquinone ring) oxygen atom of
one of the polyether/ester chains (lengths [C‚‚‚O] and [C-H‚‚‚O],
and angle [C-H‚‚‚O], 3.26 and 2.31 Å, and 171°, respectively)
as well as between one of the methylene hydrogen atoms of
the tetracationic cyclophane component and the third (counting
from the inside hydroquinone ring) oxygen atom of the opposite
polyether/ester chain (lengths [C‚‚‚O] and [C-H‚‚‚O], and angle
[C-H‚‚‚O], 3.24 and 2.35 Å, and 153°, respectively). Inspec-
tion of the packing of 34+ revealed that both ester carbonyl
oxygen atoms are involved in pairs of [C-H‚‚‚O] hydrogen
bonds to the hydrogen atoms in the â-positions with respect to
the nitrogen atoms on the bipyridinium units in the tetracationic
cyclophane components of the centrosymmetrically-related [2]-
catenane molecules. Although the molecules pack with the
acceptor-donor-acceptor-donor axes co-aligned along the
crystallographic b direction, in 34+, the usual extended polar
donor-acceptor stack is not formed. The space between the
alongside hydroquinone ring of one [2]catenane molecule and
the alongside bipyridinium unit of the next is filled by
nitromethane and benzene solvent molecules. The principal
difference between the two independent molecules of 44+ is in
Association Constants. The association constants (Ka)
(Table 3) for the complexation (Figure 8) of a series of
π-electron-rich hydroquinone-based guests by the bipyridinium-
based cyclophane [BBIPYBIXYCY][PF6]4 were determined in
1
CD3CN by either H-NMR spectroscopy or absorption spec-
troscopy in the visible region. The hydroquinone-based poly-
ether BMEEB incorporating two -CH2CH2O- ethylene link-
ages in each polyether chain is bound4 strongly (Ka ) 3800
M-1) by the tetracationic cyclophane [BBIPYBIXYCY][PF6]4.
Introduction of one ester carbonyl group into the R-, â-, or
γ-position of one or both polyether chains results4 in a decrease
of the association constant of approximately 1 order of
magnitude. On the contrary, the hydroquinone-based guest
BδCMEEB, incorporating one ester carbonyl group in the
δ-positions of both polyether/ester chains, is bound slightly more
strongly with a Ka value of 1000 M-1. Furthermore, introducing
one or two more -CH2CH2O- ethylene linkages within the
polyether/ester chains, i.e. “moving” the ester groups away from

2618 J. Am. Chem. Soc., Vol. 119, No. 11, 1997
Asakawa et al.
c
Table 2. Distancesa (Å) and Anglesa (deg) Characterizing the Molecular Geometries of the [2]Catenanes 1‚4PF6,b 3‚4PF6, and 4‚4PF6
compound
θi
θa
ψi
ψa
τi
τa
Zi‚‚‚Za
Y‚‚‚Y′
Za‚‚‚Xi
Zi‚‚‚Xi
Zi‚‚‚X′a
H‚‚‚Y
XHY
H′‚‚‚Y′
H′X′Y′
1‚4PF6
3‚4PF6
4a‚4PF6
4b‚4PF6
6
6
6
3
4
32
25
25
28
32
25
27
27
47
53
45
48
47
31
64
55
7.04
6.97
7.06
7.09
10.25
10.21
10.25
10.16
3.52
3.48
3.48
3.48
3.52
3.48
3.55
3.53
3.62
3.37
3.54
3.41
2.80
2.65
2.81
2.77
168
173
163
161
2.80
2.92
3.01
2.88
168
170
152
159
13
24
25
a The distances and angles indicated in the table are illustrated in the diagrams A, B, and C. The subscripts a and i stand for alongside and
inside, respectively.
b The X-ray crystal structure of 1‚4PF6 has been reported previously in the literature (Anelli, P. L.; Ashton, P. R.; Ballardini, R.; Balzani, V.;
Delgado, M.; Gandolfi, M. T.; Goodnow, T. T.; Kaifer, A. E.; Philp, D.; Pietraszkiewicz, M.; Prodi, L.; Reddington, M. V.; Slawin, A. M. Z.;
Spencer, N.; Stoddart, J. F.; Vincent, C.; Williams, D. J. J. Am. Chem. Soc. 1992, 114, 193-218). c Two crystallographically-independent molecules
a and b are observed for 4‚4PF6 in the solid state.
Table 3. Association Constants for the 1:1 Complexes Formed
between [BBIPYBIXYCY][PF6]4 and the π-Electron-Rich
Hydroquinone-Based Acyclic Guests at 25 °C in CD3CN, as Well
as for the 1:1 Complexes Formed between [PQT][PF6]2 and the
π-Electron-Rich Hydroquinone-Based Macrocyclic Hosts at 25 °C
in Me2CO
compound
Kaa (M-1
)
-∆G° b (kcal mol-1
)
λmaxc (nm)
BMEEBd
3800
300
320
680
520
430
130
1000
2400
4300
730
73
4.9
3.4
3.4
3.9
3.7
3.7
2.9
4.1
4.6
5.0
3.9
2.5
1.0
1.2
455
350
380
455
447
467
467
465
461
468
436
427
417
417
RCBMEEB
BRCMEEB
âCBMEEBd
BâCMEEBd
γCBMEEB
BγCMEEB
BδCMEEB
BúCMEEEB
BθCMEEEEB
BPP34C10d
âCBPP34C10d
BâCPP34C10d
BδCPP34C10
5
8
a The association constants (Ka) were evaluated at H-NMR spec-
troscopy, employing the continuous variation methodology and UV-
vis spectroscopy employing the titration methodology when the
tetracationic cyclophane [BBIPYBIXYCY][PY6]4 was used as the host
(Connors, K. A. Binding Constants; Wiley: New York, 1987). The
protons attached to the hydroquinone ring of the guests and the charge
transfer band associated with the complexes were used as the probes.
UV-vis spectroscopy was employed to evaluate the association
constants (Ka) by the titration methodology when [PQT][PF6]2 was
employed as the guest, using the charge transfer band associated with
the complexes as the probe. b Free energy (-∆G°) of complexation.
c Wavelength (λmax) corresponding to the maximum of the charge
transfer band originating from the interaction between the bipyridinium
units and the hydroquinone rings. d The values of Ka, -∆G°, and λmax
reported for the guests BMEEB, âCBMEEB, and BâCMEEB as well
as for the hosts BPP34C10, âCBPP34C10, and BâCPP34C10 are
literature values (Asakawa, M.; Ashton, P. R.; Menzer, S.; Raymo, F.
M.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. Chem. Eur. J. 1996,
2, 877-893).
1
Figure 7. Two crystallographically-independent molecules (a and b)
observed in the case of the [2]catenane 44+ in the crystal.
the hydroquinone ring, results in increasing the association
constant up to 4300 M-1 in the case of the guest BθMEEEEB.
These results suggest that the complexation of such hydro-
quinone-based guests is affected dramatically by the presence
of ester functions along the polyether/ester chains. This
depressive effect on binding is particularly evident when the
ester carbonyl group is located in the R-, â-, and γ-positions.
In the case of the complex [BRCMEEB]-[BBIPYBIXYCY]-
[PF6]4, the X-ray crystallographic analysis shows (Figure 2) a
binding geometry significantly different from that observed for
BMEEB. In both complexes, the hydroquinone ring is inserted
into the cavity of the tetracationic cyclophane giving rise to
π-π stacking and edge-to-face T-type interactions. However,
in the case of BRCMEEB, the hydroquinone ring is more steeply
inclined with respect to the mean plane of the tetracationic
cyclophane and, as a result, no hydrogen bonding stabilizing
interactions between the polyether/ester oxygen atoms of
BRCMEEB and the acidic protons HR of [BBIPYBIXYCY]-
[PF6]4 are observed. Presumably, in solution, a similar binding
geometry is retained and the absence of hydrogen bonding
stabilizing interactions accounts for the dramatic decrease in
Ka for [BRCMEEB]-[BBIPYBIXYCY][PF6]4. Furthermore, in
BRCMEEB, the ester functions are attached directly to the

Interlocked Molecular Compounds
J. Am. Chem. Soc., Vol. 119, No. 11, 1997 2619
Figure 8. Complexation of the acyclic hydroquinone-based guests by the tetracationic cyclophane [BBIPYBIXYCY][PF6]4 in solution.
aromatic ring reducing its electron density and, therefore, its
ability to sustain aromatic π-π stacking interactions. Interest-
ingly, the absorbance A and the wavelength λ of the charge
transfer band associated with [BRCMEEB]-[BBIPYBIXYCY]-
[PF6]4 (A ) 0.72 and λ ) 380 nm) are both significantly lower
than in the case of [BMEEB]-[BBIPYBIXYCY][PF6]4 (A )
0.91 and λ ) 455 nm) in MeCN at an equimolar concentration
of host and guest of 10-3 M.
tionic cyclophane [BBIPYBIXYCY][PF6]4 were also evaluated
by measuring the temperature dependence of ∆G°. In all cases,
negative values of ∆H° and positive values of T∆S° were
observed. Thus, the complexation of the hydroquinone-based
guests BMEEB, BâCMEEB, and BγCMEEB by the tetra-
cationic cyclophane [BBIPYBIXYCY][PF6]4 is enthalpically
driven. We believe that the cooperative noncovalent bonding
interactions revealed by the X-ray crystallographic analyses are
operative in solution and are responsible for the complex
formation.
The X-ray crystallographic analysis of the complex [BMEEB]-
[BBIPYBIXYCY][PF6]4 shows (Figure 1) a pair of hydrogen
bonding interactions between two centrosymmetrically-related
hydrogen atoms HR in the R-positions with respect to the
nitrogen atoms on the bipyridinium units and the oxygen atoms
Ob (Figure 8) of the two polyether/ester chains. However,
introducion of one ester carbonyl group into either the â- or
the γ-positions of the polyether/ester chains reduces the electron
density of Ob (Vide infra) directing the hydrogen bonding
interactions to the methoxy oxygen atoms Oc. Furthermore,
the [Ob-OC-CH2-Oc] linkages are forced to adopt less stable
(Vide infra) syn-periplanar conformations in order to bring Oc
into close spatial proximity with the corresponding hydrogen
atom HR. In the case of the guests BδCMEEB, BúCMEEEB,
and BθCMEEEEB, the electron density on the oxygen atoms
Ob is restored and, within the corresponding pseudorotaxanes,
hydrogen bonding interactions with the hydrogen atoms HR are
sustained by the oxygen atoms Ob, as illustrated by the X-ray
crystallographic analyses (Figures 4 and 5). Furthermore, within
the complexes between the tetracationic cyclophane [BBIPY-
BIXYCY][PF6]4 and BδCMEEB, BúCMEEEB, and
BθCMEEEEB, the linkages [O-OC-CH2-O] can retain more
stable anti-periplanar conformations. These observations sug-
gest that significant conformational changes of the guests
BâCMEEB and BγCMEEB are required in order to achieve
noncovalent bonding interactions within their corresponding
complexes, comparable to those observed in the pseudorotaxanes
incorporating BδCMEEB, BúCMEEEB, and BθCMEEEEB.
Furthermore, such conformational changes are energetically
demanding, and so, the stablilities of the corresponding
complexessi.e. the Ka valuessare significantly lower than in
the case of the other hydroquinone-based guests. The enthalpic
∆H° and entropic T∆S° contributions (Table 4) to the free
energy of binding ∆G° for the complexation of the acyclic
guests BMEEB, BâCMEEB, and BγCMEEB by the tetraca-
A similar dependence on constitution was observed for the
binding (Figure 9) of [PQT][PF6]2 by hydroquinone-based
macrocyclic receptors.4 Introducing one ester carbonyl group
into the â- or δ-positions within one or both of the polyether/
ester chains separating the hydroquinone rings results in a
dramatic decrease (Table 3) in the magnitude of the association
constant. Presumably, energy-demanding conformational changes
associated with the [O-OC-CH2-O] linkages incorporated
within the macrocyclic hosts have to be enacted in order to
maximize the noncovalent bonding interactions within the
complexes. Since these conformational changes are energeti-
cally demanding, they are reflected in a decrease in the binding
energies present in the corresponding complexes.
1
1H-NMR Spectroscopy. The H-NMR spectroscopic data
(δ values) for the 1:1 complexes formed between the π-electron-
rich hydroquinone-based acyclic guests and the tetracationic
cyclophane [BBIPYBIXYCY][PF6]4 in CD3CN at 25 °C are
listed in Table 5. The resonances associated with the hydrogen
atoms HR in the R-positions with respect to the nitrogen atoms
on the bipyridinium units of the tetracationic cyclophane host
are little changed8 (∆δ from -0.01 to +0.08 ppm) upon
complexation. On the contrary, as a result of the insertion of
a π-electron-rich hydroquinone ring guest within the cavity of
the tetracationic cyclophane host, the hydrogen atoms Hâ in the
â-positions with respect to the nitrogen atoms on the bipyri-
dinium units of the host are significantly shifted. In the case
of the strongly bound guests BMEEB,4 BδCMEEB, BúCMEEEB,
and BθCMEEEEB (Ka values of 3800, 1000, 2400, and 4300
M-1, respectively), the resonances associated with Hâ are moved
significantly upfield (∆δ ) -0.28, -0.25, -0.29, and -0.30,
respectively) as a consequence of shielding effects experienced
by these hydrogen atoms upon complexation. In the case of

2620 J. Am. Chem. Soc., Vol. 119, No. 11, 1997
Asakawa et al.
Figure 9. Complexation of [PQT][PF6]2 by the macrocyclic hydroquinone-based hosts.
Table 4. Enthalpic (∆H°) and Entropic (T∆S°) Contributionsa to
the Free Energy of Binding (∆G°) for the Complexation of the
Acyclic Guests BMEEB, BâCMEEB, and BγCMEEB by the
Tetracationic Cyclophane [BBIPYBIXYCY][PF6]4 in CD3CN at 25
°C
Table 5. 1H-NMR Spectroscopic Data (δ Values) for the
Complexes and Reference Compounds in CD3CN at 25 °C
polycationic
component
neutral
component
ArHc
a
b
compound
HR
Hâ
-∆G°
-∆H°
T∆S°
d
(kcal mol-1
)
(kcal mol-1
)
(kcal mol-1
)
[BBIPYBIXYCY][PF6]4
8.89 8.17
compound
BMEEBd
6.85
BMEEB
BâCMEEB
BγCMEEB
4.9
3.7
2.9
16.4
13.5
7.9
11.5
9.8
5.0
d
[BMEEB]-[BBIPYBIXYCY][PF6]4
8.91 7.89 4.49
7.00
8.90 8.05 6.05
7.18
8.88 8.16 6.94
6.85
8.89 8.07 5.45
6.85
8.89 8.13 6.36
6.85
8.90 8.01 5.28
6.85
8.87 8.13 6.38
6.85
8.97 7.92 4.68
6.85
RCBMEEBe
e
[RCBMEEB]-[BBIPYBIXYCY][PF6]4
BRCMEEB
[BRCMEEB]-[BBIPYBIXYCY][PF6]4
a The enthalpic (∆H°) and entropic (T∆S°) contributions to the free
energy of binding (∆G°) were calculated from a plot of ∆G° against
the temperature T. The values of ∆G° at different temperatures were
determined from the association constants measured at the correspond-
ing T values.
âCBMEEBd
d
d
[âCBMEEB]-[BBIPYBIXYCY][PF6]4
BâCMEEBd
[BâCMEEB]-[BBIPYBIXYCY][PF6]4
γCBMEEB
the less stable complexes between [BBIPYBIXYCY][PF6]4 and
the acyclic guests incorporating one ester carbonyl group in the
R-, â-, or γ-positions of both polyether chains (Ka values of
320, 520, and 130 M-1, respectively),4 the resonances associated
[γCBMEEB]-[BBIPYBIXYCY][PF6]4
BγCMEEB
[BγCMEEB]-[BBIPYBIXYCY][PF6]4
BδCMEEB
[BδCMEEB]-[BBIPYBIXYCY][PF6]4
BúCMEEEB
(8) These observations are not in conflict with the existence of [C-H‚‚‚O]
hydrogen bonding interactions between the polyether oxygen atoms and
the hydrogen atoms HR within the pseudorotaxane-like complexes and the
[2]catenanes in solution. Only two out of a total of eight HR hydrogen atoms
are involved simultaneously in [C-H‚‚‚O] hydrogen bonding interactions
in each case. Nonetheless, only one doublet is observed in the 1H-NMR
spectrum for all the eight protons HR as a result of exchange processes
which are fast on the 1H-NMR time scale. Thus, the observed chemical
shifts for the protons HR are averaged valuessi.e., the deshielding effect
caused by the [C-H‚‚‚O] hydrogen bonding interactions is “diluted”
considerably. The dynamic processes responsible for the site exchange of
the eight protons HR are (i) equilibration between complex and “free” host
and guest, (ii) tilting of the O‚‚‚O axis of the hydroquinone ring located
inside the cavity of the tetracationic cyclophane with respect to the N‚‚‚N
axes of the sandwiching bipyridinium unitssa process termed “rocking”
(see: Anelli, P. L.; Ashton, P. R.; Ballardini, R.; Balzani, V.; Delgado,
M.; Gandolfi, M. T.; Goodnow, T. T.; Kaifer, A. E.; Philp, D.; Pietraszk-
iewicz, M.; Prodi, L.; Reddington, M. V.; Slawin, A. M. Z.; Spencer, N.;
Stoddart, J. F.; Vicent, C.; Williams, D. J. J. Am. Chem. Soc. 1992, 114,
193-218), and (iii) circumrotation of the tetracationic cyclophane with
respect to the O‚‚‚O axis of the “inside” hydroquinone ring, in the case of
the pseudorotaxane-like complexes, and (i) circumrotation of the tetracationic
cyclophane through the cavity of the macrocyclic lactone, (ii) circumrotation
of the macrocyclic lactone through the cavity of the tetracationic cyclophane,
as well as (iii) “rocking”, in the case of the [2]catenanes. The 1H-NMR
spectrum of the complex [BMEEB]-[BBIPYBIXYCY][PF6]4 recorded in
CD3COCD3 at 190 Ksi.e., the lowest practical temperature in this
solventsshows only one doublet for all the eight protons HR, suggesting
[BúCMEEEB]-[BBIPYBIXYCY][PF6]4
BθCMEEEEB
8.92 7.88 4.42
6.85
[BθCMEEEEB]-[BBIPYBIXYCY][PF6]4 8.92 7.87 4.06
d
[PQT][PF6]2
8.84 8.36
BPP34C10d
6.73
d
[BPP34C10]-[PQT][PF6]2
8.80 8.07 6.44
6.77
8.83 8.32 6.71
âCBPP34C10d
d
[âCBPP34C10]-[PQT][PF6]2
BâCPP34C10d,f
[BâCPP34C10]-[PQT][PF6]2
6.79, 6.78
d,f
f
8.84 8.36 6.77, 6.76
6.77, 6.75
8.84 8.35 6.75, 6.74
BδCPP34C10f
[BδCPP34C10]-[PQT][PF6]2
a Protons attached to the bipyridinium units in the R-positions with
respect to the nitrogen atoms. b Protons attached to the bipyridinium
units in the â-positions with respect to the nitrogen atoms. c Protons
attached to the hydroquinone rings incorporated within the π-electron-
rich components. d Literature values (Asakawa, M.; Ashton, P. R.;
Menzer, S.; Raymo, F. M.; Stoddart, J. F.; White, A. J. P.; Williams,
D. J. Chem. Eur. J. 1996, 2, 877-893). e The π-electron-rich acyclic
compound RCBMEEB incorporates one hydroquinone ring which gives
1
rise, in the H-NMR spectrum, to an AA′BB′ system centered on the
δ
value listed in the table. f The π-electron-rich macrocycles
BâCPP34C10 and BδCPP34C10 incorporate two hydroquinone rings,
1
each giving rise to a singlet in the H-NMR spectrum.
1
that the dynamic processes are still fast on the H-NMR time scale at this
temperature. On the contrary, in the case of the [2]catenane 1‚4PF6, the
exchange processes are slow on the 1H-NMR time scale in CD3COCD3 at
190 K. As a result, two equally intense partially overlapped resonances are
observed for the protons HR of the bipyridinium unit located “alongside”
the cavity of the macrocyclic polyether in addition to two resonances of
equal intensities separated by a difference in chemical shift of ∆δ 0.18 for
the protons HR of the “inside” bipyridinium unit. The larger difference
between the δ values of the resonances associated with the “inside”
bipyridinium unit is, presumably, a consequence of the [C-H‚‚‚O] hydrogen
bonding interactions which involve only one of the two pairs of protons
HR.
with Hâ are weakly affected (∆δ ) -0.01, -0.04, and -0.04,
respectively). Interestingly, when the guests RCBMEEB, âCB-
MEEB,4 and γCBMEEB (Ka values of 300, 680, and 430 M-1
,
respectively) incorporating one ester carbonyl group within only
one of the two polyether/ester chains are employed, ∆δ values
(∆δ ) -0.08, -0.10, and -0.16, respectively) higher than those
observed for the related guests incorporating two ester groups
are observed in keeping with the trend in the Ka values.

Interlocked Molecular Compounds
J. Am. Chem. Soc., Vol. 119, No. 11, 1997 2621
Table 6. Free Energies of Activation for the Dynamic Processes
Associated with the [2]Catenanes 2‚4PF6, 3‚4PF6, and 4‚PF6 in
Solution
Similarly, the hydrogen atoms ArH attached to the hydroquinone
rings experience a dramatic upfield shift upon complexation as
a result of the shielding effect exerted by the sandwiching
bipyridinium units of the host. In the complexes incorporating
BMEEB, BδCMEEB, BúCMEEEB, and BθCMEEEEB, the
resonances associated with ArH are shifted by ∆δ values of
-2.36, -2.17, -2.43, and -2.79 ppm, respectively. When the
guests BRCMEEB, BâCMEEB, and BγCMEEB are employed,
the hydroquinone ring resonances are shifted by ∆δ values of
only -0.24, -0.49, and -0.47 ppm, respectively. In the case
of the guests RCBMEEB, âCBMEEB, and γCBMEEB incor-
porating only one ester carbonyl group in one of the two
polyether/ester chains, the hydroquinone ring resonances are
more significantly shifted (∆δ ) -0.95, -1.40, and -1.57 ppm,
respectively) than in the case of the related guests incorporating
two ester carbonyl groups, once again in keeping with the trend
in the Ka values.
A similar effect is observed (Table 5) for the complexation
of [PQT][PF6]2 by the hydroquinone-based macrocyclic poly-
ethers. When the macrocyclic polyether BPP34C10 is em-
ployed, the hydrogen atoms HR and Hâ of [PQT][PF6]2, as well
as the hydroquinone hydrogen atoms (ArH), are shifted upfield
(∆δ ) -0.04, -0.29, and -0.29 ppm, respectively). However,
when the macrocyclic lactones âCBPP34C10, BâCPP34C10,
and BδCPP34C10 are employed, very small chemical shift
changes are observed in the resonances associated with HR, Hâ,
and ArH, reflecting the low Ka values associated with these
complexes.
a
a
∆Gq
∆Gq
(AfB)
(BfA)
compound
(kcal mol-1
)
(kcal mol-1
)
Tcb (K)
c,d
2‚4PF6
15.1
15.5
15.5
13.8
14.7
14.8
307
295
304
c,e
3‚4PF6
e
4‚4PF6
a Free energy of activation (∆Gq(AfB)) for the interconversion of the
translational isomer A into B (see diagram below) at the coalescence
temperature. Free energy of activation (∆Gq(BfA)) for the intercon-
version of the translational isomer B into A at the coalescence
temperature. The free energies values were determined by employing
eqs 3 and 4 using the hydrogen atoms [CH2CO] of the methylene
group(s) attached to the ester carbonyl group(s) as the probes.
k(AfB)
∆Gq(AfB) ) RTc(23.759) -
∆Gq(BfA) ) RTc(23.759) -
(3)
(4)
Tc
k(BfA)
Tc
The rate constants (k(AfB)) and (k(AfB)) associated with the intercon-
version of the translational isomer A into B and Vice Versa were
determined by employing eqs 5 and 6, where PA and PB are the
populations of the translational isomers A and B, respectively, and ∆ν
is the frequency difference (Oki, M. Applications of Dynamic NMR
Spectroscopy to Organic Chemistry; VCH: Weinheim, Germany, 1985).
k(AfB) ) 2πPB∆ν
(5)
k(BfA) ) 2πPA∆ν
(6)
The asymmetry of the π-electron-rich macrocyclic compo-
nents of the [2]catenanes listed in Table 6, induced by the
presence of one or two ester carbonyl groups in the â- or
δ-positions of one or both polyether/ester chains, gives rise to
the existence of two translational isomers for each [2]catenane
in solution. However, the circumrotation of the π-electron-rich
macrocyclic component through the cavity of the tetracationic
b Coalescence temperature, Tc. c Literature values (Asakawa, M.; Ash-
ton, P. R.; Menzer, S.; Raymo, F. M.; Stoddart, J. F.; White, A. J. P.;
Williams, D. J. Chem. Eur. J. 1996, 2, 877-893). d In CD3COCD3.
e In CD3COCD3/CD3CN (7:3, v/v).
1
cyclophane component is fast on the H-NMR time scale at
room temperature. As a result, the two translational isomers
of each [2]catenane are in fast exchange at room temperature
1
and sharp averaged resonances are observed in the H-NMR
rocyclic polyether component and one of the hydrogen atoms
HR in the R-positions with respect to the nitrogen atoms on the
bipyridinium units of the tetracationic cyclophane component.
As a result of such a hydrogen bonding interaction, the
electrophilic character of the carbon atom of the related ester
carbonyl group is increased, and so, enhanced hydrolysis of the
ester function is expected within the [2]catenane. In order to
support this observation, each of the macrocyclic lactones
âCBPP34C10, BâCPP34C10, and BδCPP34C10 was heated at
50 °C in a 1:1 mixture of D2O and CD3CN and the reactions
were followed by H-NMR spectroscopy. However, the H-
NMR spectra recorded after 7 days did not reveal any significant
difference from the spectra recorded at the outset of the
experimentsi.e., the ester functions are not hydrolyzed under
these conditions. Even when the same experiments were
repeated, after adding 1 mol equiv of either [PQT][PF6]2 or
[BBIPYBIXYCY][PF6]4 to the reaction mixtures, the macro-
cyclic lactones were recovered unaltered after 7 days. However,
by contrast, treating (Figure 10) the [2]catenanes, 2‚4PF6, 3‚-
4PF6, and 4‚4PF6, under the same conditionssnamely, 50 °C
in a 1:1 mixture of D2O and CD3CNshydrolyses of the
macrocyclic lactones incorporated within the [2]catenanes occur.
The plots of the relative concentration of the [2]catenanes,
calculated by integrating the resonances associated with the
hydrogen atoms HR against time are shown in Figure 11.
Interestingly, after approximately 800 h, an equilibrium between
reagent and products is reached in all three processes. Fur-
spectra. On cooling solutions of the [2]catenanes down to -50
1
°C, the dynamic processes become slow on the H-NMR time
scale and two sets of signals, arising separately from each of
the translational isomers, can be detected in the 1H-NMR
spectrum. Integration of these resonances affords the ratios
between the translational isomers, which correspond to 4:1,
10:1, and 4:1 for 2‚4PF6,4 3‚4PF6,4 and 4‚4PF6, respectively.
As suggested by the X-ray crystallographic analyses of the [2]-
catenanes, 3‚4PF6 (Figure 8) and 4‚4PF6 (Figure 9), in all cases,
the major isomer in solution is believed to be the one bearing
the ester carbonyl group(s) proximal to the hydroquinone ring
located inside the cavity of the tetracationic cyclophane
component. This isomer preference is presumably a result of
more favorable intercomponent hydrogen bonding interactions
(Vide supra) involving the oxygen atoms of the ester carbonyl
groups. By employing the coalescence methodology,9 the free
energies of activation for the site exchange processes involving
the interconversion of the two translational isomers were
evaluated and are listed in Table 6.
1
1
Kinetic Studies. The X-ray crystallographic analysis of the
[2]catenane 4‚4PF6 revealed (Figure 7) a hydrogen bonding
interaction between the oxygen atom of one of the two ester
carbonyl groups incorporated within the π-electron-rich mac-
(9) (a) Sutherland, I. O. Ann. Rep. NMR Spectrosc. 1971, 4, 71-235.
(b) Sandstro¨m, J. Dynamic NMR Spectroscopy; Academic Press: London,
1982. (c) Oki M. Applications of Dynamic NMR Spectroscopy to Organic
Chemistry; VCH: Weinheim, Germany, 1985.

2622 J. Am. Chem. Soc., Vol. 119, No. 11, 1997
Asakawa et al.
Figure 10. Hydrolysis of the [2]catenanes (a) 2‚4PF6, (b) 3‚4PF6, and (c) 4‚4PF6.
Figure 11. Plots of the relative concentrations of the [2]catenanes (a)
2‚4PF6, (b) 3‚4PF6, and (c) 4‚4PF6 against time.
thermore, in the case of the bis-lactones incorporated within
3‚4PF6 and 4‚4PF6, only one of the two ester groups is
hydrolyzed. The HPLC chromatogram (Figure 12d) of the
reaction mixture of the [2]catenane 4‚4PF6srecorded after 800
h, that is, at equilibriumsshows only three peaks. These peaks
correspond to (i) the [2]catenane (Figure 12a), (ii) the tetraca-
tionic cyclophane [BIBIPYBIXYCY][PF6]4 (Figure 12b), and
(iii) the acyclic carboxylic acid BâCHEHEEEPEEEEB produced
as a result of the hydrolysis of only one ester group. None of
the compound BHEEEB (Figure 12c), which should be formed
Figure 12. HPLC charts of (a) 3‚4PF6, (b) the tetracationic cyclophane
[BBIPBIXYCY][PF6]4, (c) the diol BHEEEB, and (d) the carboxylic
acid BâCHEHEEEPEEEEB.
after the hydrolysis of the second ester group, is detected in the
reaction mixture. By employing a nonlinear curve-fitting
program, the kinetic and thermodynamic parameters listed in

Interlocked Molecular Compounds
J. Am. Chem. Soc., Vol. 119, No. 11, 1997 2623
Table 7. Kinetic and Thermodynamic Parameters for the Hydrolysis of the [2]Catenanes 2‚4PF6, 3‚4PF6, and 4‚4PF6 in D2O/CD3CN (1:1,
v/v) at 50 °C
c
d
∆Gq
∆Gq
∆G° f
f
r
e
compound
kfa (s-1
)
krb (s-1
)
(kcal mol-1
)
(kcal mol-1
)
Keq
(kcal mol-1
)
2‚4PF6
3‚4PF6
4‚4PF6
6.7 × 10-7
7.9 × 10-7
8.6 × 10-8
3.7 × 10-7
4.0 × 10-7
7.6 × 10-7
28.1
28.0
29.4
28.5
28.4
28.0
1.8
2.0
0.1
-0.4
-0.4
1.4
a Rate constant (kf) for the forward reaction, i.e. hydrolysis of the catenane. b Rate constant (kr) for the backward reaction, i.e. macrocyclization.
c Free energy of activation (∆Gqf) for the forward reaction, i.e. hydrolysis of the catenane. d Free energy of activation (∆Gqr) for the backward
reaction, i.e. macrocyclization. e Equilibrium constant (Keq). f Free energy of equilibrium (∆G°).
Table 8. Parameters Associated with the Electrostatic Interactionsa Occurring between the Acidic Hydrogen Atoms HR of the Cyclophane
[BBIPYBIXYCY][PF6]4 and the Polyether/ester Oxygen Atoms of the Hydroquinone-Based Guests BMEEB, BâCMEEB, BγCMEEB, and
BδCMEEB within the Corresponding [2]Pseudorotaxanes
Oa
Ob
Oc
b
compound
-iab
Oa‚‚‚HRc (Å)
-Rad (Å-1
)
-ib
Ob‚‚‚HRc (Å)
-Rbd (Å-1
)
-icb
Oc‚‚‚HRc (Å)
-Rcd (Å-1
)
BMEEB
66.5
61.1
57.0
61.9
3.20
3.74
3.21
3.23
20.8
16.3
17.8
19.2
74.0
65.9
61.0
69.7
2.23
2.90
2.74
2.39
33.2
22.7
22.3
29.2
70.0
72.0
64.0
72.8e
2.42
2.14
2.36
2.32e
28.9
33.6
27.1
31.4e
BâCMEEB
BγCMEEB
BδCMEEB
a The electrostatic interactions occurring between the hydrogen atoms HR of [BBIPYBIXYCY][PF6]4 and the polyether/ester oxygen atoms of
the guests within the [2]pseudorotaxanes are schematically illustrated in the diagram. b Relative intensities of the electrostatic potential mapped on
to the total electron density surface for the oxygen atoms Oa, Ob, and Oc, as generated with the program Spartan Version 4.1 (Spartan Version 4.1,
Wavefunction Inc., 1995). c Distance between HR and Oa, Ob, and Oc. d Ratio between i and the corresponding distance [O‚‚‚HR]. This term is
proportional to the electrostatic contribution to the energy associated with the interaction occurring between O and HR. The monotonic correlation
between the sum of Ra, Rb, and Rc and the binding energy is illustrated in the plot. e In the case of the guest BδCMEEB, Oc is the carbonyl oxygen
atom.
Table 7 were determined from the plots shown in Figure 11.
Interestingly, little difference is observed between the parameters
associated with the [2]catenanes incorporating the macrocyclic
lactones âCBPP34C10 and BâCPP34C10 comprising one ester
carbonyl group in the â-position of one and both polyether
chains, respectively. On the contrary, the rate constant for the
hydrolysis of the [2]catenane, incorporating the macrocyclic bis-
lactone BδCPP34C10 possessing one ester carbonyl group in
the δ-positions of both polyether chains, is approximately 1
order of magnitude lower. These results suggest that within
the mechanically-interlocked compoundssnamely, the [2]-
catenanessthe tetracationic cyclophane acts as a “Lewis acid”,
increasing the reactivity of the ester function(s) present within
the macrocyclic lactones as a result of hydrogen bonding
interactions. Furthermore, the difference in the rate of hydroly-
sis observed on “moving” the ester carbonyl groups from the
â- to the δ-positions along the polyether/ester chains suggests
that the strength of the hydrogen bonds is related to the location
of the ester carbonyl groups within the polyether/ester chains.10
The potential enanchment of reactivity of the ester functions
incorporated within the acyclic hydroquinone-based compounds
B(R-δ)MEEB, BúMEEEB, and BθMEEEEB, upon complex
formation with the tetracationic cyclophane [BBIPYBIXYCY]-
[PF6]4, was also investigated. However, when equimolar
amounts of [BBIPYBIXYCY][PF6]4 and any of the acyclic
guests were treated in a 1:1 mixture of D2O and CD3CN 50
°Csi.e., the conditions employed to hydrolyze the [2]-
catenanessno hydrolysis of the guests was observed at all.
These observations suggest that the tetracationic cyclophane
[BBIPYBIXYCY][PF6]4 acts only as a “Lewis acid” only when
it is mechanically-interlocked within [2]catenanes and not when
it is complexed within [2]pseudorotaxanes. Presumably, in
solution within the pseudorotaxane-like, complexes the oxygen
atoms of the ester carbonyl groups are not involved in any
hydrogen bonding interactions with the tetracationic cyclophane,
as was indeed revealed by X-ray crystallography (Vide supra)
in the solid state.
Molecular Modeling. In order to gain further insight into
the reasons for the differences in the binding energies of the
pseudorotaxane-like complexes, the structures of the hydro-
quinone-based polyether/esters BMEEB, BâCMEEB, BγCMEEB,
and BδCMEEB, obtained from the X-ray crystallographic
analyses, were subjected to a single-point semiempirical treat-
ment employing11 the AM1 Hamiltonian to calculate the relative
intensities of the electrostatic potential mapped on to the total
electron density surface of these molecules. The maximum
values ia, ib, and ic for the relative intensities of the electrostatic
potential which we have mapped out on to the total electron
density surface for the oxygen atoms Oa, Ob, and Oc, respec-
tively, together with the distances [Oa‚‚‚HR], [Ob‚‚‚HR], and
[Oc‚‚‚HR] between Oa, Ob, and Oc, respectively, and the
(10) The X-ray crystallographic analysis of the [2]catenane 3‚4PF6
revealed that the carbonyl oxygen atoms of the ester functions are involved
in pairs of intermolecular hydrogen bonding interactions, rather than
intramolecular ones, as in the case of 4‚4PF6. Nonetheless, the rate of
hydrolysis of the macrocyclic bis-lactone component is faster in the case
of 3‚4PF6. Presumably, the intramolecular hydrogen bonding interactions
responsible for the enhanced reactivity of the ester function in solution are
over-ruled in the solid state by more favorable intermolecular hydrogen
bonding interactions.
(11) Spartan V 4.1, Wavefunction, Inc., 18401 Von Karman Ave., #370
Irvine, CA 92715.

2624 J. Am. Chem. Soc., Vol. 119, No. 11, 1997
Asakawa et al.
Table 9. Calculated Potential Energy Difference between the
hydrogen atom HR closest to them in the case of BMEEB,
BâCMEEB, BγCMEEB, and BδCMEEB, are listed in Table
8. The ratios Ra, Rb, and Rc between ia, ib, and ic and the
corresponding distances [Oa‚‚‚HR], [Ob‚‚‚HR], and [Oc‚‚‚HR],
respectively, are proportional12 to the attractive electrostatic
contribution to the energy associated with the interactions
occurring between the corresponding oxygen atom and the
proximal HR. The sum of Ra, Rb, and Rc provides an estimate
of the total attractive electrostatic contribution to the [O‚‚‚HR]
interactions for a single polyether/ester chain (twice the value
of Ra + Rb + Rc yields the total attractive electrostatic
contribution for both polyether/ester chains) and its monotonic
correlation with the binding energy (Table 8) corroborates the
observations suggested by the X-ray analysessi.e., subtle
stereoelectronic changes induced by varying the location of the
carbonyl groups along the polyether/ester chains are reflected
in the stabilities of the 1:1 complexes as a result of modifications
to the geometries of the hydrogen bonding interactions between
the polyether/ester oxygen atoms and the bipyridinium hydrogen
atoms HR.
Anti-periplanar and the Syn-periplanar Conformations of Methyl
2-Methoxyacetate in the Gas Phase
method
AM1
PM3
3-21G*/HF
3-21G*/MP2
-∆Ea kcal mol-1
)
6.4
4.6
0.9
1.2
a Potential energy difference between the anti-periplanar A and syn-
periplanar B conformations calculated by employing the program
Spartan Version 4.1 (Spartan Version 4.1, Wavefunction Inc., 1995).
Electrostatic iso-surfaces of A and B are shown below.
X-ray crystallographic analyses of the pseudorotaxane-like
complexes formed between the guests BδCMEEB, BúCMEEEB,
and BθCMEEEEB and the tetracationic cyclophane [BBIPY-
BIXYCY][PF6]4 revealed (Vide supra) anti-periplanar conforma-
tions for the [O-OC-CH2-O] linkages. On the contrary, in
the case of the complexes incorporating the guests BâCMEEB
and BγCMEEB, the [O-OC-CH2-O] linkages adopt syn-
periplanar conformations. Ab initio calculations on the model
compound, methyl 2-methoxyacetate, revealed (Table 9) energy
differences favoring of the anti-periplanar conformationsi.e.,
the anti-periplanar conformation (A) is more stable than the syn-
periplanar one (B)spresumably, as a result of a stereoelectronic
effect.13 Thus, in the case of the guests BâCMEEB and
BγCMEEB, the change of the conformation of the [O-OC-
CH2-O] linkages of each polyether/ester chain from the more
stable anti- to the syn-periplanar conformation is required in
order to achieve favorable hydrogen bonding interactions
between the polyether oxygen atoms and the bipyridinium
hydrogen atoms upon complexation. Furthermore, examination
(Table 9) of the electrostatic iso-surfaces of the anti- and syn-
periplanar conformation of methyl 2-methoxyacetate revealed
an electrostatic potential surface of the anti-periplanar confor-
mation A approximately twice as large as the one for the syn-
periplanar conformation Bsi.e., the anti-periplanar conformation
is a better hydrogen bond acceptor.14 These observations are
consistent with the values for the association constants (Table
3) of the pseudorotaxane-like complexes. Low Ka values are
observed for the complexes [BâCMEEB][BBIPYBIXYCY]-
[PF6]4 and [BγCMEEB][BBIPYBI-XYCY][PF6]4 in which the
[O-OC-CH2-O] linkages of the polyether/ester chains adopt
the “less hydrogen bond accepting” syn-periplanar conformation.
Conclusions
The tetracationic cyclophane cyclobis(paraquat-p-phenylene)
binds acyclic hydroquinone-based polyethers with pseudoro-
taxane-like geometries in solution and in the solid state.
However, subtle structural changes to the guestssnamely, the
introduction of one ester function along one or both polyether
chainssaffect significantly the stereoelectronic match between
the receptor and the substrate. As a consequence, the stabilities
of the complexes are greatly affected in solution. Moreover,
varying the location of the ester function(s) along the polyether/
ester chains results in dramatic changes in the association
constants. X-ray crystallographic analyses of the pseudorotax-
anes demonstrated the geometries adopted by these complexes
in the solid state and has revealed hydrogen bonding interactions
between the polyether/ester oxygen atoms and the acidic
hydrogen atoms of the tetracationic cyclophane. However, the
geometries associated with hydrogen bonding interactions are
influenced markedly by the positions of the ester carbonyl
groups. As confirmed by molecular modeling studies, the ester
oxygen atom [CH2-O-CO] adjacent to the carbonyl group is
a weaker hydrogen bonding donor than an ether oxygen atom
[CH2-O-CH2]. Furthermore, in order to achieve such hydro-
gen bonding interactions, substantial changes in conformations,
involving torsional angles associated with [OCH2-COO] link-
ages, are required. As a result, the position of the ester carbonyl
group determines the stability and the geometry of the complex.
A similar effect was observed upon complexation of paraquat
bis(hexafluorophosphate) by macrocyclic hydroquinone-based
mono- and bis-lactones. These macrocycles have also been
incorporated within mechanically-interlocked compounds, along
with cyclobis(paraquat-p-phenylene), to afford [2]catenanes.
Again, the hydrogen bonding interactions existing between the
acidic hydrogen atoms of the the bipyridinium units and the
oxygen atoms of the ester functions are responsible for control-
(12) The electrostatic energy V associated with the attractive interaction
between two point charges q and q′ of opposite sign, separated by a distance
r, is given by eq 1, where ꢀm is the permittivity of the mediumsi.e., a
q′
4πꢀm
q
r
V )
(1)
measure of its ability to transmit an electric field (Isaacs, N. S. Physical
Organic Chemistry; Longman: Harlow, 1995). When the point charge q′
is constant, the electrostatic energy V is function of the ratio between q
and r. The values of ia, ib, and ic associated with the oxygen atoms Oa, Ob,
and Oc reported in Table 8 are proportional to the charge density at the
same point on the electron density surfacesi.e., they are proportional to q.
As the tetracationic host is the same in all the complexes, the i value for
the bipyridinium hydrogen atoms HR in the various complexes can be
considered constantsi.e., it is proportional to q′. Similarly, the interactomic
distance [O‚‚‚HR] can be used in (1) as the r value. As a result, the attractive
electrostatic contribution to any [O‚‚‚HR] interaction is proportional to the
ratio between the i value of O and the [O‚‚‚HR] distance.
(14) This effect is reminicent of the different basicity observed for syn
and anti lone pairs of carboxylates, see: (a) Zimmerman, S. C.; Cramer,
K. D. J. Am. Chem. Soc. 1988, 110, 5906-5908. (b) Huff, J. B.; Askew,
B.; Duff, R. J.; Rebek, J., Jr. J. Am. Chem. Soc. 1988, 110, 5908-5909.
(c) Li, Y.; Houk, K. N. J. Am. Chem. Soc. 1989, 111, 4505-4507. (d)
Huff, J. B.; Tadayoni, B. M.; Rebek, J., Jr. J. Am. Chem. Soc. 1991, 113,
2247-2253.
(13) For a discussion on the conformational analysis of 1,2-dimethoxy-
ethane in the gas and solution phases, see: Williams, D. J.; Hall, K. B. J.
Phys. Chem. 1996, 100, 8224-8229.

Interlocked Molecular Compounds
J. Am. Chem. Soc., Vol. 119, No. 11, 1997 2625
157.7, 145.0, 123.5, 116.2, 72.6, 72.6, 71.5, 71.2, 70.3, 69.1, 68.9, 58.9.
Anal. Calcd for C16H24O7: C, 58.53; H, 7.37. Found: C, 58.54; H,
7.42.
ling the translational isomerism associated with the [2]catenanes
and the reactivites of their ester functions. The electrophilicities
of the ester carbon atoms are greatly enhanced as a result of
these noncovalent bonding interactions. The inertness toward
hydrolysis of the macrocyclic lactones in their free forms
compares with their reactivities when incorporated within the
[2]catenanes. In addition, kinetic studies have demonstrated
that the rate of hydrolysis changes upon varying the position
of the ester carbonyl groups, i.e. by varying the geometries of
the hydrogen bonding interactions.
1-[2-(2-Methoxyethoxy)ethoxy]-4-(2-hydroxyethoxy)benzene (MEE-
HEB). MEEHB (14.0 g, 67.0 mmol) was added to a suspension of
K2CO3 (46.0 g, 335 mmol) in dry MeCN (200 mL) under N2. The
suspension was stirred vigorously for 30 min at 70 °C, and a solution
of 2-chloroethanol (12.1 g, 150 mmol) in MeCN (100 mL) was added
over 1 h. The resulting reaction mixture was heated under reflux for
5 days. After the mixture was cooled to room temperature, the
suspension was filtered and the solid was washed with MeCN (200
mL). The combined organic solutions were concentrated in vacuo, and
the residue was dissolved in CH2Cl2 (200 mL) and washed with H2O
(3 × 100 mL). The organic phase was dried with Na2SO4, and the
solvent was evaporated in vacuo. Purification of the residue by column
chromatography (SiO2, MeCO2Et/CH2Cl2, 1:20) gave MEEHEB as a
yellow oil (1.6 g, 9.4%): FABMS m/z 256 [M]+; 1H-NMR (CDCl3) δ
6.84 (4H, s), 4.10-4.07 (2H, m), 4.03-4.00 (2H, m), 3.93-3.90 (2H,
m), 3.85-3.82 (2H, m), 3.72-3.69 (2H, m), 3.59-3.56 (2H, m), 3.38
(3H, s), 2.12 (1H, br s); 13C-NMR (CDCl3) δ 153.1, 153.0, 115.7, 115.5,
71.9, 70.6, 70.0, 69.8, 68.0, 61.3, 59.0.
Experimental Section
General Methods. Chemicals were purchased from Aldrich and
used as received. Solvents were dried [MeCN (from P2O5), CH2Cl2
(from CaH2), and PhMe (from CaH2)], according to procedures
described in the literature.15 MEEHB,4 BδCtBuEEB,16 BúCtBuEEEB,
BθCtBuEEEEB,16 BδCHEEB,16 BHEEB,7 BMEEB,4 âCBMEEB,4
BâCMEEB,4 [BBIPYXY][PF6]2,7 âCBPP34C10,4 BâCBP34C10,4
4
2‚4PF6,4 and 3‚4PF6 were all prepared according to literature proce-
dures. Thin layer chromatography (TLC) was carried out using
aluminum sheets precoated with silica gel 60 F (Merck 5554). The
plates were inspected by UV light and developed with iodine vapor.
Column chromatography was carried out using silica gel 60 F (Merck
9385, 230-400 mesh). High-performance liquid chromatography
(HPLC) was carried out on a Gilson 714 system, fitted with a UV
detector. Melting points were determined on an Electrothermal 9200
apparatus and are not corrected. Elemental analyses were performed
by the University of Sheffield Microanalytical Service. Low-resolution
mass spectra were performed using a Kratos profile spectrometer
operating in electron impact (EIMS) mode. Fast atom bombardment
mass spectra (FABMS) were recorded on a Kratos MS80 spectrometer
operating at 8 keV using a xenon primary atom beam. The matrix
used was 3-nitrobenzyl alcohol (NOBA). UV-vis spectra were
recorded on a Perkin-Elmer Lambda 2 using HPLC quality solvents.
1H-NMR spectra were recorded on either a Bruker AC300 (300 MHz)
spectrometer or a Bruker AMX400 (400 MHz) spectrometer using either
the solvent or TMS as internal standards. 13C-NMR spectra were
recorded on either a Bruker AC300 (75.5 MHz) spectrometer or a
Bruker AMX400 (100.6 MHz) spectrometer using either the solvent
or TMS as internal standards. All chemical shifts are quoted in ppm
on the δ scale, and the coupling constants are expressed in hertz (Hz).
2-(2-Methoxyethoxy)acetyl Chloride. 2-(2-Methoxyethoxy)acetic
acid (14.1 g, 100 mmol) was added to a mixture of dry PhMe (100
mL) and pyridine (3 drops). Oxalyl chloride (25.4 g, 127 mmol) was
added at room temperature, and the reaction mixture was stirred for
24 h. The solution was filtered through Celite, and the solvent was
evaporated in vacuo to give 2-(2-methoxyethoxy)acetyl chloride as a
yellow oil (13.2 g, 86%), which was employed in the following step
without further purification: 1H-NMR (CDCl3) δ 4.48 (2H, s), 3.77-
3.74 (2H, m), 3.58-3.55 (2H, m), 3.36 (3H, s); 13C-NMR (CDCl3) δ
172.0, 76.6, 71.9, 71.3, 59.0.
1-[2-(2-Methoxyethoxy)ethoxy]-4-[2-[(methoxymethylene)carboxy]-
ethoxy]benzene (γCBMEEB). A solution of 2-methoxyacetyl chloride
(670 mg, 5.90 mmol) in dry CH2Cl2 (50 mL) was added at -5 °C over
1 h to a vigorously stirred solution of MEEHEB (1.00 g, 45.7 mmol)
and Et3N (660 mg, 6.5 mmol) in dry CH2Cl2 (100 mL). The stirring
was continued for 20 h during which time the temperature rose gradually
to room temperature. Thereafter, the solution was poured into ice-
water (200 mL). The organic phase was washed with a saturated
aqueous solution (200 mL) of NaHCO3 and dried (Na2SO4). The
evaporation of the solvent in vacuo afforded a residue which was
purified by column chromatography (SiO2, MeCO2Et/CH2Cl2, 1:30) to
give γCBMEEB as a yellow oil (940 mg, 74%): EIMS m/z 328 [M]+;
1H-NMR (CD3CN) δ 6.87 (4H, s), 4.43-4.40 (2H, m), 4.16-4.13 (2H,
m), 4.05-4.02 (2H, m), 4.03 (2H, s), 3.777-3.74 (2H, m), 3.63-3.60
(2H, m), 3.50-3.47 (2H, m), 3.37 (3H, s), 3.31 (3H, s); 13C-NMR (CD3-
CN) δ 171.2, 154.4, 153.8, 116.7, 116.5, 72.7, 71.2, 70.2, 69.0, 67.6,
63.9, 59.4, 58.9. Anal. Calcd for C16H24O7: C, 58.53; H, 7.37.
Found: C, 58.62; H, 7.24.
1,4-Bis[[(2-methoxyethoxy)methylene]carboxy]benzene
(BrCMEEB). A solution of 2-(2-methoxyethoxy)acetyl chloride (13.0
g, 85.2 mmol) in dry CH2Cl2 (50 mL) was added at -5 °C over 30
min to a vigorously stirred solution of 1/4DHB (4.6 g, 42.0 mmol)
and Et3N (8.69 g, 55.2 mmol) in dry CH2Cl2 (100 mL). The stirring
was continued for 15 h, during which time the temperature raised
gradually to room temperature and then the solution was poured into
ice-water (300 mL). The organic phase was washed with a saturated
aqueous solution of NaHCO3 (200 mL) and dried (Na2SO4). The solent
was removed in vacuo, and the purification of the residue by
recrystallization from hexane/CH2Cl2 gave BRCMEEB as a crystalline
white solid (13.7 g, 95%): mp 96-97 °C; FABMS m/z 342 [M]+;
1H-NMR (CDCl3) δ 7.13 (4H, s), 4.40 (4H, s), 3.83-3.80 (4H, m),
3.62-3.59 (4H, m), 3.40 (6H, s); 13C-NMR (CDCl3) δ 168.8, 147.7,
122.3, 72.0, 71.1, 68.7, 59.0. Anal. Calcd for C16H22O8: C, 56.14;
H, 6.48. Found: C, 55.81; H, 6.23.
1,4-Bis[2-[(methoxymethylene)carboxy]ethoxy]benzene
(BγCMEEB). A solution of methoxyacetyl chloride (5.00 g, 46.1
mmol) in dry CH2Cl2 (30 mL) was added at -5 °C over 30 min to a
vigorously stirred solution of BHEB (3.00 g, 15.4 mmol) and Et3N
(5.10 g, 50.7 mmol) in dry CH2Cl2 (100 mL) and dry THF (150 mL).
The stirring was continued for 20 h, during which time the temperature
rose gradually to room temperature. Thereafter, the solution was poured
into ice-water (200 mL). The organic phase was washed with a
saturated aqueous solution of NaHCO3 (200 mL) and dried with Na2-
SO4. The evaporation of the solvent in vacuo afforded a residue which
was purified by column chromatography (SiO2, MeCO2Et/CH2Cl2, 1:5).
Crystallization of the residue from hexane/CH2Cl2 gave BγCMEEB
as a white crystalline solid (2.7 g, 52%): mp 61-63 °C; FABMS m/z
342 [M]+; 1H-NMR (CDCl3) δ 6.85 (4H, s), 4.53-4.49 (4H, m), 4.17-
4.13 (4H, m), 4.09 (4H, s), 3.46 (6H, s); 13C-NMR (CDCl3) δ 170.2,
153.0, 115.8, 69.7, 66.5, 63.2, 59.4. Anal. Calcd for C16H22O8: C,
56.14; H, 6.48. Found: C, 56.17; H, 6.53.
1-[2-(2-Methoxyethoxy)ethoxy]-4-[[2-methoxyethoxy)methylene]-
carboxy]benzene (rCBMEEB). A solution of 2-(2-methoxyethoxy)-
acetyl chloride (15.0 g, 98.3 mmol) in dry CH2Cl2 (50 mL) was added
at -5 °C over 1 h to a vigorously stirred solution of MEEHB (9.70 g,
45.7 mmol) and Et3N (5.60 g, 55.3 mmol) in dry CH2Cl2 (100 mL).
The stirring was continued for 20 h during which time the temperature
rose gradually to room temperature. Thereafter, the solution was poured
into ice-water (200 mL). The organic phase was washed with a
saturated aqueous solution (200 mL) of NaHCO3 and dried (Na2SO4).
The evaporation of the solvent in vacuo afforded RCBMEEB as a pale
1
yellow oil (13.5 g, 90%): EIMS m/z 328 [M]+; H-NMR (CDCl3) δ
7.07-7.02 (2H, m), 6.98-6.93 (2H, m), 4.35 (2H, s), 4.11-4.08 (2H,
m), 3.78-3.75 (2H, m), 3.73-3.70 (2H, m), 3.64-3.61 (2H, m), 3.55-
3.49 (4H, m), 3.32 (3H, s), 3.30 (3H, s); 13C-NMR (CDCl3) δ 170.6,
(15) Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell, A. R.
Practical Organic Chemistry; Longman: New York, 1989.
(16) Asakawa, M.; Ashton, P. R.; Brown, G. R.; Hayes, W.; Menzer,
S.; Stoddart, J.F.; White, A. J. P.; Williams, D. J. AdV. Mater. 1996, 1,
37-41.

2626 J. Am. Chem. Soc., Vol. 119, No. 11, 1997
Asakawa et al.
Table 10. Crystal Data, Collection, and Refinement Parameters for the [2]Pseudorotaxanes Incorporating the π-Electron-Deficient Cyclophane
[BBIPYBIXYCY][PF6]4 and the π-Electron-Rich Acyclic Compounds Listed in Turn
data
BMEEB
BRCMEEB
BâCMEEB
BγCMEEB
BδCMEEB
BθCMEEEEB
formula‚4PF6
solvent
formula weight
lattice type
space group
T (K)
C52H58N4O6
2MeCN
1497.0
triclinic
P1h
C52H54N4O8
4MeCN
1607.1
monoclinic
P21/n
C52H54N4O8
4MeCN‚0.5H2O
1615.1
triclinic
P1h
293
C52H54N4O8
H2O
C52H54N4O8
3.5MeCN
1586.6
triclinic
P1h
C60H70N4O12
1460.9
triclinic
P1h
1619.1
triclinic
P1h
293
293
293
293
293
cell dimensions
a (Å)
b (Å)
11.566(2)
12.556(3)
13.901(4)
110.95(2)
92.33(2)
113.87(2)
1683.0(7)
1a
1.477
766
2.104
3.5-55.0
15.376(6)
11.337(3)
20.772(6)
10.785(2)
13.497(3)
13.975(2)
91.61(2)
103.19(1)
110.33(1)
1836.4(6)
1a
1.460
826
2.008
3.3-55.0
11.007(2)
12.226(2)
13.471(2)
88.83(2)
70.13(1)
66.70(1)
1552.1(4)
1a
1.563
744
2.294
3.5-55.0
11.037(1)
13.861(1)
14.174(1)
77.672(3)
72.146(7)
76.014(7)
1979.9(3)
1a
1.331
811
1.846
3.3-55.0
11.736(3)
12.417(3)
13.909(4)
100.71(2)
106.75(2)
110.65(2)
1720.2(7)
1a
1.563
830
2.166
3.5-60.0
c (Å)
R (deg)
â (deg)
90.51(1)
γ (deg)
V (Å3)
3621.0(2)
2a
1.474
1644
2.029
Z
Dc (g cm-3
F(000)
)
µ (mm-1
)
θ range (deg)
no. of unique reflns
measd
3.6-58.0
4231
3126
5028
4166
4620
3468
3901
3009
4768
3449
5103
4098
obsdb
no. of variables
R1 (%)
495
6.77
17.25
0.096, 2.258
556
6.64
18.61
0.102, 3.890
523
8.70
24.02
0.146, 3.264
470
8.73
24.87
0.130, 4.622
481
14.70
40.24
0.313, 5.144
470
8.41
22.23
0.086, 6.049
wR2 (%)
a, bc
b
a The molecule has crystallographic Ci symmetry. |Fo| > 4σ(|Fo|). c Weighting factors.
1,4-Bis[2-[(methoxycarbonyl)methoxy]ethoxy]benzene
(BδCMEEB). BδCtBuEEB (1.09 g, 2.60 mmol) was added to a
solution of Na (1.0 mg, 0.04 mmol) in MeOH (100 mL), and the
solution was heated under reflux for 2 h. After the mixture was cooled
to room temperature, the solvent was evaporated in vacuo. Purification
of the residue by column chromatography (SiO2, MeCO2Et/CH2Cl2,
1:30) gave BδCMEEB as a white solid (710 mg, 80%): EIMS m/z
of the residue by column chromatography (SiO2, hexane/Me2CO, 6:4)
gave a solid, which was recrystallized from hexane/Me2CO (6:4) to
give BδCPP34C10 as a crystalline white solid (760 mg, 14%): mp 88
1
°C; FABMS m/z 564 [M]+; H NMR (CD3CN) δ 6.78 (4H, s), 6.75
(4H, s), 4.28-4.25 (4H, m), 4.15 (4H, s), 3.99-3.95 (8H, m), 3.80-
3.70 (12H, m); 13C NMR (CD3CN) δ 171.3, 154.1, 153.9, 116.5, 116.4,
70.6, 70.4, 69.7, 69.6, 69.0, 64.7. Anal. Calcd for C28H36O12: C, 59.57;
H, 6.43. Found: C, 59.46; H, 6.27.
1
342 [M]+; H NMR (CDCl3) δ 6.85 (4H, s), 4.16 (4H, s), 4.08-4.05
(4H, m), 3.83-3.81 (4H, m), 3.68 (6H, s); 13C NMR (CDCl3) δ 171.7,
154.1, 116.5, 70.8, 69.1, 68.9, 52.2. Anal. Calcd for C16H22O8: C,
56.14; H, 6.48. Found: C, 56.23; H, 6.52.
{[2]-[BδCPP34C10]-[BBIPYBIXYCY]catenane}[PF6]4 (4‚4PF6).
A solution of BδCPP34C10 (198 mg, 0.350 mmol), [BPYPYXY][PF6]2
(742 mg, 1.05 mmol), BBB (360 mg, 1.37 mmol), and NaI (3 mg,
21.0 µmol) in dry DMF (20 mL) was stirred at room temperature for
14 days. The solvent was removed in vacuo, and the resulting solid
residue was purified by column chromatography (SiO2, MeOH/2 M
NH4Cl/MeNO2, 7:2:1) to afford 4‚4PF6, after counterion exchange, as
a red crystalline solid (332 mg, 57%): mp 295 °C (dec); FABMS m/z
1665 [M]+, 1519 [M - PF6]+, 1374 [M - 2PF6]+, 1229 [M - 3PF6]+;
1H NMR (CD3COCD3/CD3CN, 7:3, v/v) δ 9.16 (8H, d, J ) 7 Hz),
8.03 (8H, d, J ) 7 Hz), 7.97 (8H, s), 5.95 (8H, s), 4.65 (4H, br s), 4.46
(4H, br s), 3.90 (8H, br s), 3.78-3.75 (8H, m), 3.67-3.65 (4H, m);
13C NMR (CD3COCD3/CD3CN, 7:3, v/v) δ 147.2, 145.5, 137.6, 131.8,
126.6, 115.8, 114.0, 70.8, 70.3, 68.3, 65.7, 64.5. Anal. Calcd for
C64H68F24N4O12P4: C, 46.17; H, 4.12; N, 3.37. Found: C, 46.30; H,
4.06; N, 3.35.
X-ray Crystallography. In the case of the [2]pseudorotaxanes and
of the [2]catenane 4‚4PF6, single crystals suitable for X-ray crystal-
lographic analysis were grown by vapor diffusion of i-Pr2O into a
MeCN solution of the compound. In the case of the [2]catenane 3‚-
4PF6, single crystals suitable for X-ray crystallographic analysis were
grown by vapor diffusion of benzene into a MeNO2 solution of the
[2]catenane. X-ray diffraction measurements were performed on either
a Siemens P4/PC or a Siemens P4/PC RA instruments using Cu KR
radiation (λ ) 1.541 78 Å) and ω-scans. The data were corrected for
Lorentz and polarization factors but not for absorption. The structures
were solved by direct methods and refined by full-matrix least-squares
based F2, using the SHELXTL package version 5.0.17 Hydrogen atoms
were placed in calculated postions (C-H distance 0.96 Å) and assigned
isotropic thermal parameters [U(H) ) 1.2 Ueq(C) and for methyl groups
U(H) ) 1.5 Ueq(C)]. The crystal data and the data collection and
1,4-Bis[2-[2-[(methoxycarbonyl)methoxy]ethoxy]ethoxy]-
benzene (BúCMEEEB). BúCBMEEEB was obtained as a clear oil
(0.29 g, 89%) from the tert-butyl diester BúCtBuEEEB (0.302 g, 0.75
mmol) by employing a procedure identical to that used for the
preparation of BδCMEEB: FABMS m/z 430 [M]+; 1H NMR (CDCl3)
δ 3.67-3.71 (14H, m), 3.75-3.80 (4H, m), 3.99-4.04 (4H, m), 4.12
(4H, s), 6.77 (4H, s); 13C NMR (CDCl3) δ 51.7, 67.9, 68.6, 69.8, 70.7,
70.9, 115.5, 153.0, 170.9. Anal. Calcd for C20H30O10: C, 55.81; H,
7.03. Found: C, 55.66; H, 6.97.
1,4-Bis[2-[2-[2-[(methoxycarbonyl)methoxy]ethoxy]ethoxy]ethoxy]-
benzene (BθCBMEEEEB). BθCBMEEEEB was obtained as a clear
oil (0.28 g, 85%) from the tert-butyl diester BθCBtBuEEEEB (0.315
g, 0.64 mmol) by employing a procedure identical to that used for the
preparation of BδCBMEEB: FABMS m/z 518 [M]+; 1H NMR (CDCl3)
δ 3.61-3.72 (22H, m), 3.76-3.81 (4H, m), 4.00-4.05 (4H, m), 4.12
(4H, s), 6.80 (4H, s); 13C NMR (CDCl3) δ 51.7, 68.1, 68.6, 69.9, 70.6,
70.7, 70.9, 115.6, 153.1, 168.1, 170.9. Anal. Calcd for C24H38O12:
C, 55.59; H, 7.39. Found: C, 55.71; H, 7.43.
1,4,7,10,13,18,21,24,27,30-Decaoxa-6,25-dioxo[13,13]-
paracyclophane (BδCPP34C10). BδCBHEEB (4.40 g, 14.0 mmol)
was suspended in a mixture of dry PhMe (200 mL) and dry pyridine
(3 drops). Oxalyl chloride (14.2 g, 112 mmol) was added at room
temperature and under N2 to the suspension. The temperature was
raised to 50 °C and stirring maintained for 21 h. After the mixture
was cooled to room temperature, the solution was concentrated to give
a yellow solid, which was redissolved in dry PhMe (250 mL). The
PhMe solution of the bis-acid chloride and a solution of BHEEB (2.86
g, 10.0 mmol) in dry PhMe (250 mL) were added over 2 h and 30
min, from two separate dropping funnels, to vigorously stirred dry PhMe
(500 mL) mantained at 50 °C under N2. The stirring was continued
for 48 h, and then the solution was concentrated in vacuo. Purification
(17) Sheldrick, G. M. SHELXTL Version 5.0, Siemens Analytical X-ray
Instruments Inc., 1994.

Interlocked Molecular Compounds
J. Am. Chem. Soc., Vol. 119, No. 11, 1997 2627
Table 11. Crystal Data, Collection, and Refinement Parameters for
the [2]Catenanes 3‚4PF6 and 4‚4PF6
Variations Methodology. A solution of [BBIPYBIXYCY][PF6]4 and
a solution of the π-electron-rich acyclic guest with identical concentra-
tions (∼10-3 M) were prepared using CD3CN as the solvent. By
employing the two stock solutions, several new solutions with the same
total volumes, but differing in the ratios of the two components (from
1:9 to 9:1, host:guest), were prepared. The chemical shifts of the
protons attached to the hydroquinone ring of the guest were measured
by 1H-NMR spectroscopy at the temperature T. The correlation between
the mole fraction of the guest and the chemical shift change for the
probe protons was used18 to evaluate the association constant (Ka) in a
nonlinear curve-fitting program.
data
3‚4PF6
C64H68N4O12
PhH‚5.5MeNO2‚0.5H2O
4‚4PF6
formula‚4PF6
solvent
formula weight
lattice type
space group
T (K)
C64H68N4O12
2MeCN
1747.2
monoclinic
P21/c
2087.96
triclinic
P1h
198
203
cell dimensions
a (Å)
b (Å)
13.865(1)
18.057(1)
19.865(3)
90.11(1)
104.51(1)
98.52(1)
4757.9
2
1.460
2150
1.81
2.3-55.0
39.907(3)
14.011(1)
27.333(4)
General Method for the Determination of the Kinetic and
Thermodynamic Parameters Associated with the Hydrolysis of the
[2]Catenanes. A solution of the [2]catenane of known concentration
(C0 ) 0.003 mM) in CD3CN/D2O (1:1, v/v, 0.5 mL) was heated at 50
c (Å)
R (deg)
â (deg)
98.52(1)
1
γ (deg)
°C for ca. 1500 h. The reaction was followed by H-NMR spectros-
V (Å3)
15114(1)
8a
1.536
7168
2.028
2.3-58.0
copy, and the molar concentration C of the [2]catenane, calculated by
integrating the resonances associated with the protons in the R-positions
with respect to the nitrogen atoms on the bipyridinium units, was plotted
against time (t). Fitting of the data by means of a nonlinear curve-
fitting program employing eq 219 where Ce is the molar concentration
of the [2]catenane at equilibrium, afforded the rate constant (kf) of
the hydrolysis reaction.
Z
Dc (g cm-3
F(000)
)
µ (mm-1
)
θ range (deg)
no. of unique reflns
measd
11825
8182
21036
13254
obsdb
kfCt
Ce
no. of variables
R1 (%)
1267
9.91
26.94
0.197, 12.969
2053
9.09
22.57
0.123, 41.203
Ce e
- Ce
C ) C0 -
(2)
kfCt
wR2 (%)
a, bc
Ce
e
b
a There are two crystallographically independent molecules. |Fo|
Molecular Modeling. The initial structures for the calculations were
obtained from the X-ray crystallographic coordinates of the corre-
sponding pseudorotaxane-like complexes. The bond orders were
inserted into the structures and counterions and solvent molecules were
removed. The resulting files were subjected to single-point calculations
using the AM1 Hamiltonian resident within Spartan,11 with the option
for the calculation of the electrostatic surfaces activated. The generation
of the points of maximum electrostatic interaction and the creation of
the electrostatic iso-surfaces were achieved using the graphic options
of Spartan. The two conformations of the model compound, methyl
2-methoxyacetate, were generated within the Spartan builder module
and ab initio calculations at the 6-31G*/MP2 level were performed
again within Spartan.
> 4σ(|Fo|). c Weighting factors.
refinement parameters are listed in Tables 10 and 11. In the case of
the [2]pseudorotaxane [BδMEEB]-[BBIPYBIXYCY][PF6]4, 3.5 MeCN
solvent molecules are disordered in eight positions. All full-weight
non-hydrogen atoms were refined anisotropically. In the case of the
[2]pseudorotaxanes [BMEEB]-[BBIPYBIXYCY][PF6]4, [BγMEEB]-
[BBIPYBIXYCY][PF6]4, and [BRMEEB]-[BBIPYBIXYCY][PF6]4, the
disorder observed in the hexafluorophosphate counterions was resolved
by refining the counterions in two orientations with reduced occupancy.
All non-hydrogen atoms were refined anisotropically. In the case of
the [2]catenane 3‚4PF6, the hexafluorophosphate counterions were
located in five positions, four in general positions and one on a center
of symmetry. One of the hexafluorophosphate counterions in general
positions was assigned half-weight occupancy. All non-hydrogen atoms
were refined anisotropically. In the case of the [2]catenane 4‚4PF6,
seven of the eight hexafluorophosphate counterions were in general
positions and two in special positions with half weight occupancy. All
non-hydrogen atoms were refined anisotropically.
Acknowledgment. This research was supported by the
Biotechnology and Biological Sciences Research Council, by
the Engineering and Physical Sciences Research Council, by
the European Community Human Capital and Mobility Pro-
gramme, and by the Ciba-Geigy Foundation (Japan) for the
Promotion of Science.
General Method for the Determination of the Association
Constants by UV-Vis Spectroscopy Employing the Titration
Methodology. A series of solutions with constant concentrations
(∼10-3 M) of the host and containing different amounts of guest (from
∼10-4 to 10-2 M) in either CD3CN or Me2CO were prepared. The
absorbance at the wavelength (λmax) corresponding to the maximum of
the charge-transfer band for the 1:1 complex was measured for all the
solutions at the same temperature T. The correlation between the
absorbance and the guest concentration was used18 to evaluate the
association constants (Ka) using a nonlinear curve-fitting program.
General Method for the Determination of the Association
Supporting Information Available: Figures illustrating (i)
the pairs of hydrogen bonding interactions linking adjacent [2]-
pseudorotaxanes and [2]catenanes in the crystal and (ii) donor-
acceptor stacks propagating along the b crystallographic direc-
tion in one of the [2]catenanes and tables listing atomic
coordinates, temperature factors, bond lengths and angles, and
torsion angles (80 pages). See any current masthead page for
ordering and Internet access instructions.
JA962937Z
1
Constants by H-NMR Spectroscopy Employing the Continuous
(19) Laidler, K. J. Chemical Kinetics; Harper Collins Publisher: New
(18) Connors, K. A. Binding Constants; Wiley: New York, 1987.
York, 1987.