Thermodynamic forecasting of mechanically interlocked switches

Article abstract of DOI:10.1039/b911874h

Mechanically interlocked molecular (MIM) switches in the form of bistable [2]rotaxanes and [2]catenanes have proven to be - when incorporated in molecular electronic devices (MEDs) and in nanoelectromechanical systems (NEMS) - a realistic and viable alternative to the silicon chip density challenge. Structural modifications and chemical environment can have a large impact on the relaxation thermodynamics of the molecular motions, such as translation and circumrotation in bistable rotaxanes and catenanes responsible for the operation of devices based on MIMs. The effects of structural modifications on the difference in free energy (ΔG^o) for the equilibrium processes in switchable MIMs can be predicted by considering, firstly, the interactions present in their precursor pseudorotaxanes. By employing isothermal titration microcalorimetry (ITC) to investigate the thermodynamic parameters governing pseudorotaxane formation for a series of monosubstituted, acceptor host cyclophanes with various donor guests, in conjunction with X-ray crystallographic data, an obvious link between the noncovalent bonding interactions in pseudorotaxanes and MIMs that survive following the formation of the mechanical bond can be identified. It follows that the changes (ΔΔG^o values) in the difference of free energy during the formation of different pseudorotaxanes can subsequently be extrapolated to predict ΔG^o values for the thermodynamics associated with switching in analogous MIM switches, employing the same donor-acceptor recognition components. In this manner, a systematic and predictive thermodynamic approach to designing and tuning switchable MIMs and MIM-based materials has been established. Additionally, these thermodynamic relationships are reminiscent of the long forgotten concept of the 'parachor' as a molecular descriptor with respect to the additivity of physical properties in chemical systems dealing specifically with quantitative structure property-activity relationships (QSPR/QSAR).

Full text of DOI:10.1039/b911874h

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Volume 7 | Number 21 | 7 November 2009 | Pages 4321–4548
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J. Fraser Stoddart et al.
Thermodynamic forecasting of
mechanically interlocked switches
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www.rsc.org/obc | Organic & Biomolecular Chemistry
Thermodynamic forecasting of mechanically interlocked switches†
Mark A. Olson,‡a Adam B. Braunschweig,‡a Taichi Ikeda,b Lei Fang,a Ali Trabolsi,a Alexandra M. Z. Slawin,c
Saeed I. Khand and J. Fraser Stoddart*a
Received 17th June 2009, Accepted 23rd July 2009
First published as an Advance Article on the web 3rd September 2009
DOI: 10.1039/b911874h
Mechanically interlocked molecular (MIM) switches in the form of bistable [2]rotaxanes and
[2]catenanes have proven to be—when incorporated in molecular electronic devices (MEDs) and in
nanoelectromechanical systems (NEMS)—a realistic and viable alternative to the silicon chip density
challenge. Structural modifications and chemical environment can have a large impact on the relaxation
thermodynamics of the molecular motions, such as translation and circumrotation in bistable rotaxanes
and catenanes responsible for the operation of devices based on MIMs. The effects of structural
modifications on the difference in free energy (DGo) for the equilibrium processes in switchable MIMs
can be predicted by considering, firstly, the interactions present in their precursor pseudorotaxanes. By
employing isothermal titration microcalorimetry (ITC) to investigate the thermodynamic parameters
governing pseudorotaxane formation for a series of monosubstituted, acceptor host cyclophanes with
various donor guests, in conjunction with X-ray crystallographic data, an obvious link between the
noncovalent bonding interactions in pseudorotaxanes and MIMs that survive following the formation
of the mechanical bond can be identified. It follows that the changes (DDGo values) in the difference of
free energy during the formation of different pseudorotaxanes can subsequently be extrapolated to
predict DGo values for the thermodynamics associated with switching in analogous MIM switches,
employing the same donor–acceptor recognition components. In this manner, a systematic and
predictive thermodynamic approach to designing and tuning switchable MIMs and MIM-based
materials has been established. Additionally, these thermodynamic relationships are reminiscent of the
long forgotten concept of the ‘parachor’ as a molecular descriptor with respect to the additivity of
physical properties in chemical systems dealing specifically with quantitative structure property-activity
relationships (QSPR/QSAR).
structural modifications to bistable molecular switches affect
their device behaviour, there is a knowledge gap surrounding the
Introduction
Mechanically interlocked molecules (MIMs)1 have a rich evo-
consequences of these changes on device properties. Structure–
lutionary history, encompassing single-station rotaxanes and
activity investigations, which shed light on this relationship, could
catenanes,2 degenerate molecular shuttles,3 and ultimately bistable
lead to more complex MIMs with advanced properties and
molecular switches.4 The potential for molecular electronics,5 and
applications.
other applications,6 where these molecules have been incorpo-
The structural parameters that control association constants
rated and can be addressed by chemical,7 electrochemical,8 and
photochemical9 means, is the result of the ability to tune the
properties of the molecules themselves through subtle synthetic
manipulations. These structural modifications play10 a key role in
the ground-state equilibrium thermodynamics of the molecular
switches, which, in turn, carry over to device5,6 behaviour. Since
there are only a few examples of investigations relating to how
(Ka) in host–guest11 complexes can be understood experimentally
by comparing the free energy of binding (DGo) between different
host and guest components. The utility of host–guest binding
studies is that they provide a straightforward, thermodynamic
understanding of the parameters that affect such binding. An
exemplary study by Cram et al.,12 on the binding of primary
alkylammonium ion guests in crown ether hosts led to the
concepts of preorganisation and complementarity,13 laying the
groundwork for the field of supramolecular chemistry.11 Herein,
we intend to show how similar structure–activity investiga-
tions of the binding of donor–acceptor pseudorotaxanes can
have an analogous impact on the emerging field of MIMs as
switches.
aDepartment of Chemistry, Northwestern University, 2145 Sheridan Road,
Evanston, IL 60208-3113, USA). E-mail: stoddart@northwestern.edu;
Fax: +1-847-491-1009; Tel: +1-847-491-3793
bOrganic Nanomaterials Center, National Institute for Materials Science,
1-1 Namiki, Tsukuba, 305-0044, Japan
cSchool of Chemistry, University of St. Andrews, Purdie Bulding, St.
Andrews, Fife, UK KY16 9ST
Pseudorotaxanes14 are supramolecular complexes which consist
of a linear guest that is threaded and bound within a macrocyclic
host by one or more noncovalent bonding interactions, and this
host–guest system is the fundamental, functional precursor that
leads, under the guise of templation, to the formation of rotaxanes
dDepartment of Chemistry and Biochemistry, University of California, Los
Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095-1569, USA
† CCDC reference numbers 720651–720653. For crystallographic data in
CIF or other electronic format see DOI: 10.1039/b911874h
‡ These authors contributed equally to this work.
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©

and catenanes.1–4 In the case of donor–acceptor MIM switches—
based on the preferential binding of the cyclobis(paraquat-p-
phenylene) (CBPQT4+) tetracationic cyclophane with the elec-
trochemically active tetrathiafulvalene (TTF) recognition unit
over the dioxynaphthalene (DNP) unit2,4b–i,10—the difference in
the free energy (DGo) between these two recognition units can
be modelled experimentally by comparing (Fig. 1) the free
energy of binding with the diethyleneglycol-disubstituted tetrathi-
afulvalene (TTF-DEG) and diethyleneglycol-disubstituted 1,5-
dihydroxynaphthalene (DNP-DEG) with the host component
CBPQT4+ during pseudorotaxane formation. Bistable molecu-
lar switches, based on these TTF-DEGÃCBPQT4+ and DNP-
DEGÃCBPQT4+ binding motifs,2,4b–i,10 have proven4–6 to be excel-
lent molecular switches. Switching of these bistable systems can be
achieved10 using either chemical7 or electrochemical8 stimuli. The
ground-state co-conformation (GSCC), in which the CBPQT4+
ring binds preferentially to the TTF recognition unit, is in equilib-
rium with the metastable-state co-conformation (MSCC), in which
the CBPQT4+ ring encircles the DNP unit.10a,c This equilibrium
between the GSCC and the MSCC at 298 K corresponds10a,c to
a ratio of 9 : 1, or a DGo value of about 1.6 kcal mol-1, when
the CBPQT4+ ring is free to distribute itself between the TTF and
DNP recognition units. Calculating the DGo of bistable systems
from the DDGo of the supramolecular host–guest behavior, we find
that DGoGSCC/MSCC ª (DGoDNP-DEGÃCBPQT - DGoTTF-DEGÃCBPQT) is roughly
1.6 kcal mol-1. The experimentally determined DGo for the bistable
[2]catenane that uses the same recognition motifs is 1.5 ( 0.2) kcal
mol-1, which is in very good agreement with the value predicted by
this simple quantitative relation. The pseudorotaxanes form15 as a
result of [p ◊ ◊ ◊ p], [C–H ◊ ◊ ◊ p], and [C–H ◊ ◊ ◊ O] interactions between
the p-electron deficient host CBPQT4+ and p-electron rich guests,
(TTF-DEG) or (DNP-DEG). Structural modifications16 to either
of the recognition units, and/or the cyclophane affects the Ka
of complexation, rendering it possible to tune, alter and predict
the thermodynamic equilibria of the resulting MIM switches, and
consequently, molecular switch-based device performance.
structural modifications of bistable [2]catenanes, and also bistable
[2]rotaxanes, which will permit further transformations, is the
functionalisation of the CBPQT4+ ring, at a single ortho position
on one of the p-xylyl rings. This strategy has been exploited
successfully for attaching molecular switches to surfaces and
onto gold nanoparticles through the covalent modification of the
CBPQT4+ ring, as opposed to the dumbbell, and has resulted
in a linear artificial molecular muscle17a and nanoparticulated
switches.17b Since the extent to which covalent modification of
the CBPQT4+ ring affects guest binding, and thus switching
in MIMs has not been studied to any great extent, such an
investigation would help to answer the following questions:
(1) do the steric effects of appending bulky substituents onto the
host alter the binding of guests, and (2) what is the potential for
new supramolecular/molecular systems which benefit from these
functionalised CBPQT+4 rings? It is cumbersome and impractical,
however, to synthesise the series of MIMs required to answer these
questions. A more rational approach is to study the binding of
the individual components as pseudorotaxanes and subsequently
extrapolate to the properties of the potential MIMs.
The research reported herein describes a systematic approach
to designing and tuning switchable MIMs and MIM-based
materials by looking initially at the interactions present in their
precursor pseudorotaxanes. This approach bridges the knowledge
gap between the binding of supramolecular systems11,13 and the
switchable, mechanically bound4 molecules. We (1) describe the use
of a library of CBPQT4+-based hosts in order to understand the
effects of substituents on pseudorotaxane formation with a variety
of guests using isothermal titration microcalorimetry (ITC) and
electrochemistry. The DDGo values between different host–guest
complexes can subsequently be extrapolated to predict the switch-
ing thermodynamics of analogous MIM switches, employing the
same donor–acceptor recognition components. Concurrently, we
(2) look to X-ray crystallographic data to illuminate in detail
the relationship between supermolecules, i.e., the pseudorotax-
anes, and MIMs. Finally, we (3) investigate experimentally the
ground-state equilibrium thermodynamics of bistable molecular
switches appended to a polymer side-chain by a structurally
modified CBPQT4+ ring to validate this predictive thermodynamic
approach to designing MIM switches in a sterically demanding
environment.
Bistable, donor-acceptor MIMs4 are usually the end product
of a multistep synthesis and, as a result, are rarely carried on
to further chemical transformations. While modifications16 to the
guest components are well known, few examples17 of modifications
to the CBPQT4+ skeleton exist. A straightforward approach to
Fig. 1 A comparison of the potential-energy surfaces illustrating (i) two independent host–guest pseudorotaxanes in which the free-energy difference
DDGo for TTFÃCBPQT4+ and DNPÃCBPQT4+ correspond to (ii) the DGo for GSCC and MSCC in the bistable [2]catenane incorporating the same
recognition units, and is defined against a normal coordinate Q, representing circumrotation from the GSCC to the MSCC.
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Results and discussion
Structural modification of the host component
The syntheses of 1,4-bis(bromomethyl)-benzene containing OMe,
13,18 CO2H, 14,19 CO2Et, 1119 and Br, 1220 substituents were
carried out as previously described in the literature. The synthesis
of the dibromides is shown in Scheme 1. The phenyl-substituted
p-xylene derivative 8 was synthesised by a Suzuki coupling between
phenyl boronic acid and 2,5-dimethylbromobenzene as reported
previously.21 The 1,4-bis(bromomethyl)benzene derivative 10 is of
particular significance because it is an example of appending a
functional group, a phenyl ring, using a Pd-catalysed coupling to a
bromine-functionalised 1,4-bis(bromomethyl)benzene derivative
and, eventually, onto the CBPQT4+ periphery, a strategy which has
the potential to enable the attachment of many functional groups
with direct conjugation into the aryl ring of the cyclophane. Dibro-
mides 9 and 10 were prepared by radical bromination of the appro-
priate ortho-substituted 1,4-dimethyl benzene. The substituted 1,4-
dimethyl benzenes were mixed with N-bromosuccinimide (NBS)
and 2,2¢-azobis(2-methylpropionitrile) (AIBN) in CH2Cl2 and
kept under a sodium lamp for 1 day. After the resulting red solution
had been filtered to remove the white succinimide precipitate and
concentrated in vacuo, the resulting orange solid was recrystallised
twice in cyclohexane. The dibromide 9 could not be isolated as a
pure compound, but its presence in the mixture was confirmed by
mass spectrometry. The syntheses of the substituted tetracationic
cyclophane hosts 1–7·4PF6 are also shown in Scheme 1. Hosts
Scheme 1 Template-directed syntheses of the CBPQT4+-based host
library, in which CBPQT4+ has been functionalised at the single ortho
position on one of the p-xylyl rings (R).
monomer 19 in 80% yield. ATRP of monomer 19 using ethyl-
2-bromoisobutyrate as the initiator and 4,4¢-di(tert-butyl)-2,2¢-
bipyridine as the ligand, with CuBr in Me2CO gave the desired
polymer 20 in 68% yield. It is worth noting at this point that
compound 7·4PF6 does not survive the polymerisation conditions,
necessitating post-polymerisation modification of the polymer
backbone. Size exclusion chromatography (SEC) analysis of 20
showed a monomodal peak with a Mw = 55 000 g mol-1 and Mn =
39,000 g mol-1, PDI = 1.4.
With the aid of autocatalysis,23 promoted in part by anchimeric
assistance22 during polytriazole formation, polymer 20 was taken
to 100% coverage with the alkyne-derivatised CBPQT4+ 7·4PF6 in
◦
DMF-d7 at 60 C, in the presence of stoichiometric amounts of
25i
6·4PF6,19 and 7·4PF6 were synthesised as previously reported.
CuI with an NMR tube serving as the reaction vessel (Scheme 2).
1
Generally, the cyclophanes were prepared by mixing the 1,4-
bis(bromomethyl) derivatives with 1·2PF6 in the presence of an
excess of DNP-DEG 17 (3 equiv.) in DMF at high-pressure
(10–15 kbars).
The reaction progress was monitored by H NMR spectroscopy
1
(Fig. 2a–c). The signals in the H NMR spectrum of 21·nPF6
begin to broaden at the onset of the click reaction (Fig. 2b) and
are significantly broadened after 3 h (Fig. 2c). The disappearance
An azide-functionalised side-chain polymethacrylate22 was
synthesised via atom transfer radical polymerisation (ATRP)22
(Scheme 2). Starting with 2-(2-(2-azidoethoxy)-ethoxy)ethanol
18, esterification with methacryloyl chloride gave the azide
of the propargyl proton (–CO2CH2C CH, d = 3.75 ppm)
≡
of unreacted 7·4PF6 can be observed with the simultaneous
appearance of a broad singlet (d = 8.55 ppm) for the triazole
proton. Additionally, the chemical shift of the propargyl methylene
Scheme 2 Synthesis of the side-chain azide-functionalised methacrylate polymer followed by the click functionalisation of azide polymer 20 (n ª 160)
with the alkyne-functionalised CBPQT4+ derivative 7·4PF6 for the formation of the side-chain polyCBPQT4+ 21·nPF6 (n ª 160).
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by SEC, coupled with detection by multi-angle light scattering
(SEC-MALS)24 of 21·nPF6 leads to an Mw of (9.30 0.19) ¥ 105 g
mol-1, an Mn value of (6.10 0.30) ¥ 105 g mol-1, and a PDI of 1.5
0.1. Assuming the click reaction25 proceeds to complete conversion
and, based on the molar ratio of the azide functions to the alkyne-
functionalised cyclophane 7·4PF6, a theoretical Mn of 300,000 g
mol-1 for 21·nPF6 was calculated, a value which agrees with that
estimated from end-group analysis by 1H NMR spectroscopy.
Predicting the thermodynamics of mechanical switching
The ability to derive the thermodynamics of switching in MIMs
from the thermodynamic binding properties of the components
is a valuable tool that enables the rational design of donor–
acceptor bistable [2]catenanes. Experimentally, predicting DGo
for MIMs is best achieved10c by studying the difference in the
binding energies (DDGo) between the guest components—TTF-
DEG and DNP-DEG—with the host component CBPQT4+. The
thermodynamic parameters (Ka, DGo, DHo, DSo) determined by
ITC,26 for a library of CBPQT4+ derivatives (Scheme 3) that
have been structurally modified at a single ortho position on one
of the p-xylyl rings reveals (Table 1) the steric and electronic
effects of the substitution (R), compared with CBPQT4+ itself
(R = H). For all the hosts substituted, the binding strengths
are always the greatest when the guest is TTF-DEG, followed
by DNP-DEG, and finally by TTF—a trend that is identical
to the trends observed with CBPQT4+ itself. With a variety of
hosts, the differences in the DGo values of complexes with TTF
varied by no more than 0.5 kcal mol-1. However, the range
of DGo values increased to approximately 1 kcal mol-1 when
diethylene glycol chains are appended to the guests. Structural
modifications to the host cyclophane decreases the association
constant for the formation of the corresponding pseudorotaxane,
with the bulky phenyl substituent causing the largest decrease
in binding. For the substituents (R), the electron-withdrawing
(donating) ability—quantified by the Hammet constant,27 s—is
an indicator of how the oxidation potential of TTF0→TTF∑+ shifts
Fig. 2 Stacked 1H NMR spectra recorded in DMF-d7 at 298 K following
the click reaction for the formation of 21·nPF6 at (a) time = 0, (b) time =
1 h, and (c) time = 3 h.
≡
protons (–CO2CH2C CH, d = 5.15 ppm) of unreacted 7·4PF6 can
also be observed at d = 5.6 ppm in 21·nPF6 for the –CO2CH2–
triazole–protons. The protons in the bismethylene unit in the
oligoethylene chain closest to the azide function (–OCH2CH2N3,
d = 3.45 ppm and –OCH2CH2N3, d = 3.69 ppm) can also be
observed to have undergone (–OCH2CH2–triazole–, d = 4.70 ppm;
–OCH2CH2–triazole–, d = 4.00 ppm) sizable downfield shifts
upon triazole formation. Both the broadening of the peaks for the
protons and their chemical shifts in unreacted 7·4PF6, and of the
polymer 20 protons, indicate complete conversion after 3 h, with
no further spectroscopic changes being evident after 24 h. Analysis
Table 1 Thermodynamic binding dataa corresponding to the complexation between the CBPQT4+ derivatives and TTF, TTF-DEG, and DNP-DEG
guests in MeCN determined by isothermal titration microcalorimetry at 298 K
CBPQT4+b
1·4PF6
2·4PF6
3·4PF6
4·4PF6
7·4PF6
22·nPF6
TTF
Ka/¥ 103 M-1
6.91 0.18
-10.6 0.1
-5.4 0.1
3.80 1.12
-11.6 1.1
-6.6 1.1
2.19 0.68
-7.57 0.23
-2.6 0.1
3.47 0.07
-10.5 0.2
-5.7 0.2
4.99 0.09
-9.64 0.31
-4.6 0.3
—
—
—
—
—
—
—
—
DHo/kcal mol-1
TDSo/kcal mol-1
DGo298 K/kcal mol-1
TTF-DEG
-5.27 0.03
-4.91 0.05
-4.94 0.13
-4.79 0.06
-5.07 0.01
Ka/¥ 103 M-1
380 22.0
-14.2 0.1
-6.6 0.1
212.7 0.9
-13.6 0.9
-6.3 1.0
160.5 8.1
-12.1 0.1
-5.0 0.2
217.5 3.5
-14.1 0.1
-6.8 0.1
348.0 21.0
-13.4 0.4
-5.8 0.5
114.7 1.1
-11.4 0.1
-4.5 0.1
55.4 4.7
-9.66 0.22
-3.2 0.3
DHo/kcal mol-1
TDSo/kcal mol-1
DGo298 K/kcal mol-1
DNP-DEG
-7.66 0.07
-7.23 0.27
-7.09 0.05
-7.29 0.01
-7.57 0.02
-6.92 0.05
-6.49 0.05
Ka/¥ 103 M-1
36.4 0.3
-15.4 0.1
-9.1 0.1
13.1 2.2
-15.3 0.7
-9.7 0.8
2.19 0.1
-12.9 0.6
-8.4 0.7
12.9 0.4
-14.5 0.1
-8.9 0.1
17.0 4.2
-14.1 0.2
-8.3 0.2
13.4 1.9
-13.9 0.6
-8.3 0.5
8.02 0.8
-14.2 1.5
-8.9 1.5
DHo/kcal mol-1
TDSo/kcal mol-1
DGo298 K/kcal mol-1
-6.26 0.04
-5.62 0.09
-4.57 0.02
-5.61 0.04
-5.79 0.02
-5.65 0.07
-5.33 0.05
a A 0.39 mM standard solution for all CBPQT4+ derivatives was used for all titrations into which solutions of various concentrations of guest were added
in 5 mL aliquots (4.7 mM TTF, 3.2 mM TTF-DEG; 3.9 mM DNP-DEG). Hosts 5·4PF6 and 6·4PF6 were not measured because of low yield and low
binding respectively. Fits were performed using Microcal LLC software. The stoichiometry of all complexes was between 0.99 and 1.02 indicating a 1 : 1
complex is formed. b Binding data on CBPQT4+ where R = H was obtained from previously published results.10c
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Table 2 Linear free energy relationships (LFERs): A comparison of the electronic (Hammett Constants (smeta)) and steric (Winstein–Holness A values;
steric taft parameters (Es)) contributions to the binding strength (Ka) of TTF-DEG with CBPQT4+ for a variety of substituents (R) appended onto the
CBPQT4+ ring
27
b
Host
R
s
E
1/2/Va
Ka/¥ 103 M-1
A value/kcal mol-128
Es
CBPQT·4PF6
1·4PF6
H
Me
Ph
CO2Et
Br
0.00
-0.07
0.06
0.36
0.37
0.36
0.34
0.39
0.41
0.40
380.0 22.0
212.7 0.9
160.5 8.1
217.5 3.5
348.0 21.0
0.00
1.74
2.80
1.15
1.24
0.00
-2.55
—
2·4PF6
3·4PF6
4·4PF6
0.48–0.67
0.01
a The first oxidation potentials of TTF…CBPQT4+ derivatives were obtained from a 0.4 mM solution of hosts and a 5 mM solution of TTF samples
dissolved in MeCN (0.1 M TBAPF6) using a glassy carbon working electrode and a Ag/AgCl reference electrode. b Taft parameters for R = CO2Et have
not been reported.
as a result of changes to the electronic structure of the substituted
CBPQT4+. Table 2 lists the oxidation potential of TTF0→TTF∑+
as TTF resides within the cavity of CBPQT4+ along with the s
value of the substituent. The host with the substituent that is
the least electron-withdrawing, Me (s = -0.07) has the lowest
measured potential for the oxidation of TTF, and as the electron-
withdrawing ability of the substituent increases, so too does the
first oxidation potential of TTF0 in the [2]pseudorotaxane. The
cyclophanes with the most electron-withdrawing substituents—
3·4PF6 (s = 0.36) and 4·4PF6 (s = 0.37)—cause the TTF0→TTF∑+
oxidation potential to shift anodically compared to CBPQT4+
derivatives with less electron-withdrawing substituents. This study
demonstrates that small changes to the CBPQT4+ constitution
alters the first oxidation potential of TTF0 by up to 60 mV as a
result of changes in electronic structure that occur from adding a
single substituent to the CBPQT4+ skeleton. A linear relationship,
however, cannot be discerned from a Hammett plot constructed
from known Hammett constants (s) and the experimentally deter-
mined binding constants (Ka), since pseudorotaxane formation is
not solely governed by electronic effects, but can also be influenced
by steric interactions between the substituent and the guests.
Linear free energy relationships (LFERs) describing steric size for
each substituent (R)—quantified by both the Winstein–Holness
A values,28 and steric Taft parameters29 (Es)—suggests (Table 2)
that pseudorotaxane formation is strongly perturbed as a function
of steric hindrance. Previous investigations have highlighted15 the
importance of [C–H ◊ ◊ ◊ O] interactions during pseudorotaxane
formation between the oligoethyleneglycol oxygen atoms and the
methylene hydrogen atoms in CBPQT4+ in establishing a strong
association constant with guests TTF-DEG and DNP-DEG. The
solid-state crystal superstructure (Fig. 3b) of DNP-DEGÃ14+
reveals that the source of the weaker binding is a result of the loss
of a [C–H ◊ ◊ ◊ O] interaction since the glycol chain is disrupted to
avoid unfavourable steric interactions with the R group, whereas
the oligoethylene glycol chains wrap1 the CBPQT4+ ring at the
methylene positions. Indeed we find that 1·4PF6 experiences
weaker binding interactions (Table 1) with TTF-DEG (212.7
0.97) ¥ 103 M-1 and DNP-DEG (13.1 2.20) ¥ 103 M-1 compared
to that of CBPQT4+ (380.0 22.0) ¥ 103 M-1 and (36.4 0.25) ¥
103 M-1, respectively.10c
The thermodynamic parameters26 obtained by ITC during
pseudorotaxane formation are listed in Table 1 for each of the
CBPQT4+ derivatives. The difference in the free energies of binding
(DDGo) between TTF-DEG versus DNP-DEG have been shown
to correlate10a,c directly to the DGo values for the GSCC versus
MSCC for the corresponding mechanically interlocked bistable
switch, such that DDGo ª DGopredicted. The binding data indicate
that substitution at the ortho position of one p-xylylene ring
disrupts the [C–H ◊ ◊ ◊ O] interaction, reducing binding. However,
for bistable MIMs, this reduction in binding strength does not
result in a change in DDGo because binding with TTF-DEG
and DNP-DEG are reduced equally. Scheme 4 illustrates the
thermodynamic equilibrium between the GSCC and the MSCC
for bistable [2]catenanes that have been structurally modified
Scheme 3 Pseudorotaxane formation between the CBPQT4+ hosts and the diethyleneglycol-disubstituted tetrathiafulvalene (TTF-DEG) and
diethyleneglycol-disubstituted 1,5-dihydroxynaphthalene (DNP-DEG).
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at the ortho position of the p-xylylene unit, and the predicted
DGo values for the structures. These DGo
values for the
predicted
bistable [2]catenanes agree well with the free energy profiles
for molecular motions in bistable molecules obtained by
Goddard et al.30 using molecular dynamic simulations, and
from previous experiments10a,c using bistable [2]rotaxanes
in a variable temperature cyclic voltammetry study. These
predicted results demonstrate that modification at the ortho
position of CBPQT4+ should not perturb significantly the
switching behaviour, suggesting that molecular switches with
ortho-substituted CBPQT4+ rings are indeed candidates for
future device applications. To what extent these predictions
correlate with the actual experimental values for DGo in bistable
[2]catenanes must now be considered. To validate directly these
predictions on a bistable [2]catenane, the alkyne-functionalised
dibromide precursor 15 was used to synthesise the corresponding
alkyne-derivatised bistable [2]catenane 23·4PF6 in order to
study its switching behaviour as a small molecule [2]catenane.
Further support for the thermodynamic relationship between
the pseudorotaxanes and catenanes following the formation of
the mechanical bond was obtained31 by synthesising a side-chain
poly[2]catenane using the alkyne-derivatised bistable [2]catenane
23·4PF6 precursor, and studying its ground state equilibrium and
thermodynamic properties.
Structural modification of the bistable [2]catenane
In order to form 23·4PF6 by way of template-directed synthesis32
(Scheme 5), 16·2PF6 was added to a solution of the dibromide 15
and macrocycle 22 in dry DMF. The reaction mixture was stirred
1
for a week. The H–1H g-DQF-COSY (Fig. 4b) of 23·4PF6 in
CD3CN at 298 K reveals correlation peaks between the a and b
protons of the CBPQT4+ ring. The peaks for the protons H-3/7
and H-4/8 of the DNP recognition unit are hidden underneath the
signals for the p-xylylene protons of the CBPQT4+ ring in the 1H
NMR spectrum (Fig. 4a). The COSY spectrum (Fig. 4b) shows
clearly the correlation peaks for the overlapping H-3/7 and H-4/8
protons of DNP. Correlations between the propargyl methylene
protons and the unreacted alkyne proton can also be observed.
Correlations among the glycol chain protons can be detected but
are not well-resolved.
Fig.
3
Stick representations of the solid-state superstructures of
(a) TTFÃ14+ and (b) DNP-DEGÃ14+ pseudorotaxanes. Additional methyl
groups attached to 14+ reflect disorder in the crystal.
Scheme 4 Translating the thermodynamics from supramolecular host–guest behaviour (DDGo) to predicted free energy of binding (DGopredicted) for an
interlocked bistable catenane library, where the host CBPQT4+ has been functionalised at the single ortho position on one of the p-xylyl rings (R).
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Scheme 5 Template-directed synthesis of the alkyne-functionalised bistable [2]catenane.
h
Slow vapour diffusion of i-Pr2O into a MeCN solution of
23·4PF6 afforded green crystals suitable for X-ray analysis (Fig. 5).
Of the two configurational isomers, only the “trans” isomer of the
disubstituted TTF on the two-station crown ether macrocycle is
observed4b in the solid-state structure of 23·4PF6. The alkyne-
functionalised [2]catenane is stabilised by the same [p ◊ ◊ ◊ p],
[C–H ◊ ◊ ◊ p] and [C–H ◊ ◊ ◊ O] interactions that are also present1a in
the psuedorotaxane model complexes. In fact, a closer examina-
tion of the solid-state crystal superstructure of pseudorotaxanes
DNP-DEGÃ1·4PF6 and TTFÃ1·4PF6 (Fig. 6a–b) reveals that the
guests adopt1a the same co-conformation within the host CBPQT4+
as the DNP and TTF binding sites within the alkyne-derivatised
[2]catenane 23·4PF6, including identical values (Table 3) for the
[H ◊ ◊ ◊ Oc] and [H ◊ ◊ ◊ Oe] bond distances, and the [C–H ◊ ◊ ◊ Od]
bond angle. The discrepancy in the second [C–H ◊ ◊ ◊ Of] bond
angle, however, is a result of the guests residing in a crown ether
macrocycle as opposed to the linear thread of the pseudorotaxane.
The observed difference in the [p ◊ ◊ ◊ p ] bond distance is a result of
the DNP recognition unit no longer residing within the CBPQT4+
ring as the guest in the interlocked species. The solid-state crystal
structure (Fig. 5) of 23·4PF6 also reveals that the source of the
weaker binding during pseudorotaxane formation is a result of
the loss of a [C–H ◊ ◊ ◊ O] interaction since the glycol chain is
displaced to avoid unfavourable steric interactions with the R
group on the host, which results in an unusual kink in the glycol
chain of the p-electron rich macrocycle whereas the solid-state
crystal structures of similar underivatised bistable [2]catenanes4b
have no such kink. These observations illustrate the obvious link1a
between the noncovalent bonding interactions in pseudorotaxanes
and MIMs that survive following the formation of the mechanical
bonds. Furthermore, the solid-state packing of 23·4PF6 (Fig. 7) is
comprised of intermolecular donor–acceptor [p ◊ ◊ ◊ p] interactions
between the outside electron-deficient bipyridinium units and the
alongside electron rich DNP units of adjacent [2]catenanes. These
Table 3 Comparison of the crystallographic parameters of the solid-state superstructures for the pseudorotaxanes DNP-DEGÃ1·PF6, TTFÃ1·PF6 and
bistable [2]catenane 23·4PF6
a
a
b
DNP-DEGÃ1·4PF6
TTFÃ1·4PF6
23·4PF6
Formula
Mass
C67H67N10O6(4PF6)
C43H38N4S4(4PF6)
1392.79
P21/n
Ci
10.8498 (8)
19.3989 (14)
13.8729 (10)
—
—
—
—
—
—
3.80
C74H78N4O12S4·6.5H2O·C6H14O(4PF6)
1697.26
P21/n
Ci
13.83834 (9)
23.2237 (16)
13.0531 (9)
2.38
152
2.46
142
2.57
2142.80
P21/c
—
Space group
Symmetry
˚
a/A
14.216 (4)
54.971 (12)
13.678 (4)
2.33
156
2.35
175
—
3.53
3.80
˚
b/A
˚
c/A
c
˚
[H ◊ ◊ ◊ O] /A
[C–H ◊ ◊ ◊ O]d/◦
e
˚
[H ◊ ◊ ◊ O] /A
[C–H ◊ ◊ ◊ O]f/◦
g
˚
[C–H ◊ ◊ ◊ p] /A
h
˚
˚
[p ◊ ◊ ◊ p] /A
3.76
—
i
[p ◊ ◊ ◊ p] /A
a See Fig. 3. b See Fig. 5. c Length refers to the [H ◊ ◊ ◊ O] interactions between O3 of the glycol chain of the DNP guest/station and the methylene hydrogen
of the host. d Angle refers to the [C–H ◊ ◊ ◊ O] interactions between O3 of the glycol chain of the DNP guest/station and the methylene hydrogen of the
host. e Length refers to the [H ◊ ◊ ◊ O] interactions between O2 of the glycol chain of the DNP guest/TTF station and the Ha on the bipyridine of the host.
f Angle refers to the [C–H ◊ ◊ ◊ O] interactions between O3 of the glycol chain of the DNP guest/TTF station and the Ha on the bipyridine of the host.
g Length refers to the [C–H ◊ ◊ ◊ p] interactions between H1 of the naphthalene rings of DNP-DEG and the aryl rings of the host. h Length refers to the
[p ◊ ◊ ◊ p] interactions between naphthalene rings of DNP-DEG and the aryl rings of the host. i Length refers to the [p ◊ ◊ ◊ p] interactions between TTF guest
and the aryl rings of the host.
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Fig. 6 Side-on views of the solid-state superstructure of (a) TTFÃ14+ and
(b) DNP-DEGÃ14+ pseudorotaxanes showing the co-conformations of
host and guests when bound within the CBPQT4+ host cavity. Additional
methyl groups attached to 14+ reflect disorder in the crystal.
Fig. 4 (a) 1H NMR spectrum of 23·PF6 in CD3CN at 298 K. (b) The
1H–1H g-DQF-COSY spectrum of 23·PF6 in CD3CN at 298 K.
Fig. 7 (a) A space-filling representation of the packing of the alkyne-func-
tionalised bistable [2]catenane 234+ molecule in the solid-state, illustrating
the intermolecular donor–acceptor [p ◊ ◊ ◊ p] interactions between the DNP
recognition unit (red ∫ D) sitting outside the CBPQT4+ host which contains
a TTF recognition unit (green ∫ D) with the outside Bipy2+ unit of the
CBPQT4+ ring. (b) A graphical representation of the polar stack present
in the solid-state of 234+
.
The synthesis (Scheme 6) of the bistable side-chain
poly[2]catenane proceeded much like the synthesis of the side-
chain polyCBPQT4+ 21·nPF6. Polymer 20 was taken to 27%
side-chain modification with the alkyne-derivatised [2]catenane
23·4PF6 in DMF-d7 at 60 ◦C, in the presence of stoichiometric
CuI, again with an NMR tube serving as the reaction vessel. The
click reaction progress was monitored by 1H NMR spectroscopy
(Fig. 8a–d). The resonances in the 1H NMR spectrum (Fig. 8a) of
24·nPF6 begin to broaden at the onset of the click reaction, and
Fig. 5 A stick representation of the solid-state crystal structure of the
alkyne-functionalised bistable [2]catenane 234+
.
intermolecular interactions may also contribute to the previously
observed31 aggregation of bistable side-chain poly[2]catenanes
in solution, but more importantly they serve as a reminder
highlighting the presence of the noncovalent bonding interactions
that are present not only in the psuedorotaxanes, but also in MIMs
as well.
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Fig. 8 Stacked 1H NMR spectra in DMF-d7 at 298 K following the click
reaction that leads to the formation of 24·nPF6 at (a) time = 0, (b) time =
1 h, (c) time = 3 h, and (d) after capping the remaining azide moieties with
methyl propargyl ether.
4.70 ppm) sizable downfield shifts upon triazole ring formation.
Both the broadening of the peaks for the protons and the chemical
shifts of the protons in unreacted 23·4PF6, and of the polymer
20 protons indicate complete conversion after 3 h, with no
further spectroscopic changes evident after 24 h. Following the
functionalisation of 20 with 23·4PF6, the unreacted azides can be
capped by reacting the product with methyl propargyl ether. This
step (Fig. 8d) shows a dramatic increase in the peak areas for
the triazole protons (d = 8.55 ppm), as well as for the side-chain
bismethylene protons closest to the azide moiety (–OCH2CH2–
triazole–, d = 4.70 ppm), and the appearance of a broad resonance
for the methyl protons (–triazole–CH2OCH3, d = 1.19 ppm).
Analysis by SEC-MALS24 of 24·nPF6 produces a Mw value of
(1.30 0.07) ¥ 106 g mol-1, a Mn value of (8.70 0.61) ¥ 105 g
mol-1, and a PDI of 1.5 0.1. Assuming the click reaction proceeds
to complete conversion and, based on the molar ratio of the
azide functions to the alkyne-functionalised cyclophane 7·4PF6,
a theoretical Mn of 128 000 g mol-1 for 24·nPF6 was calculated, a
value which agrees with that estimated from end-group analysis
by 1H NMR spectroscopy.
Scheme 6 Click functionalisation of polymer 20 (n ꢀ 160) with the
alkyne-functionalised bistable [2]catenane 23·4PF6 for the formation of
24·nPF6 (x ꢀ 42, y ꢀ 118).
Ground state equilibrium thermodynamics
Tetrathiafulvalene can undergo4b–i,10 a two-electron oxidation
process (TTF → TTF∑+ → TTF2+), generating cationic species,
at which point switching through circumrotation in 23·4PF6
and 24·nPF6 of the macrocyclic polyether with respect to the
CBPQT4+ ring occurs. Upon reduction of the cationic species
back to the neutral form, the MSCC relaxes to the equilibrium
mixture of the GSCC and MSCC.4b–i,10 Switching of the GSCC
to the MSCC can be achieved electrochemically or chemically.
are significantly broadened after 3 h. Additionally, the chemical
≡
shift of the propargyl methylene protons (–CO2CH2C CH, d =
5.15 ppm) in unreacted 23·4PF6 can be observed at d = 5.6 ppm
in 24·nPF6 for the –CO2CH2–triazole–protons. The signals for
the protons in the bismethylene unit in the oligoethylene chain
closest to the azide funtion (–OCH2CH2N3, d = 3.45 ppm) can
also be observed to have undergone (–OCH2CH2–triazole–, d =
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Table 4 Ground-state equilibrium thermodynamic parameters (DHo, DSo, DGo298K) obtained after analysis of variable-temperature UV-vis experiments
Species
DHoa/kcal mol-1
TDSob/kcal mol-1
DGo c/kcal mol-1
DGo
d/kcal mol-1
predicted
298K
23·4PF6
24·nPF6
3.9 ( 0.1)
3.8 ( 0.1)
2.4 ( 0.2)
2.2 ( 0.1)
1.5 ( 0.2)
1.6 ( 0.1)
1.3 ( 0.1)
1.2 ( 0.1)
a Obtained from a linear van’t Hoff plot where the slope of the line is equal to -DHo/R. b Obtained from a linear van’t Hoff plot where the the intercept is
equal DSo/R. c Calculated from the Gibbs free energy identity DGo = DHo - TDSo. d Predicted from the difference in the free energies of binding (DDGo)
between TTF-DEG versus DNP-DEG with hosts 7·4PF6 and 22·nPF6 obtained by ITC in MeCN at 298 K.
The thermochromic properties of both the 23·4PF6 and 24·nPF6
were examined (Fig. 10) by variable temperature (VT) UV-vis
spectroscopy in DMF in order to quantify the ground-state
equilibrium thermodynamic parameters. The CT band situated
at 812 nm is characteristic10b of the (GSCC), whereas the (MSCC)
produces a characteristic10b CT band at 475 nm in DMF. Upon
cooling the solution, the TTFÃCBPQT4+ CT band (e = 4000 L
mol-1 cm-1) increases in intensity, while the DNPÃCBPQT4+ CT
band decreases. This observation indicates that the equilibrium
between the translational isomers favors the GSCC at lower
temperatures. Upon heating, the opposite trend is observed. With
1
the aid of VT H NMR spectra (Fig. 9) recorded to determine
the equilibrium constant for the GSCC/MSCC ratio in 23·4PF6
by monitoring the DNP 2/6 proton resonances (d ª 6.7 ppm)
at 298 K, van’t Hoff plots were constructed33 (Fig. 10a–b inset)
Fig. 10 (a) Variable temperature UV-vis spectra of the alkyne-function-
alised [2]catenane 23·4PF6 and (b) the side-chain poly[2]catenane 24·nPF6
(2 ¥ 10-4M, DMF), illustrating the temperature-dependent equilibrium
between GSCC (TTFÃCBPQT4+ charge transfer band at 800 nm) and
MSCC (DNPÃCBPQT4+ charge transfer band at 480 nm). Linear van’t
Hoff plots for 23·4PF6 (R2 = 0.996) and 24·nPF6 (R2 = 0.996) for the
thermally induced GSCC → MSCC equilibrium change was employed
to calculate the DGo298K, DHo, and DSo values for the process and are
tabulated in the Table 4.
in order to obtain (Table 4) the standard enthalpy (DHo) and
standard entropy (TDSo) changes for the GSCC→MSCC process.
The GSCC→MSCC processes in 23·4PF6 and 24·nPF6 correspond
to DGo values of 1.5 ( 0.2) and 1.6 ( 0.1) kcal mol-1, respectively.
Van’t Hoff plots constructed using integration of the resonance
1
peaks from the VT H NMR experiment for 23·4PF6 also leads
1
to a DGo value of ª 1.6 kcal mol-1. Attempts at VT H NMR
characterisation of 24·nPF6 to probe switching proved impractical
as a consequence of overlapping resonances and characteristic
broadening of high molecular weight polymers. The observed
Fig. 9 Partial variable temperature 1H NMR stacked spectra of 23·4PF6
DGo values for both 23·4PF6 and 24·nPF6, namely 1.5 ( 0.24)
taken in CD3CN showing the temperature-dependent equilibrium between
and 1.6 ( 0.05) kcal mol-1, respectively, agree well with the
predicted values found (Table 4) by determining the DDGo of
the GSCC and the MSCC by using the H-2/6 protons of the DNP
recognition unit as probe protons.
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the pseudorotaxane components. Additionally the data in Table 4
also indicate that the GSCC→MSCC switching process for both
23·4PF6 and 24·nPF6 is enthalpy driven as indicated by the larger
Experimental
Materials and methods
enthalpic contribution over the entropic contribution (DHo
=
All solvents (Fischer Scientific) were dried prior to use. All reagents
and starting materials were purchased from Aldrich or VWR and
used without further purification. 6·4PF6,19 7·4PF6,25h 8,18 11,19
12,20 13,18 14,19 15,25h 16·2PF6,25h 17,25h 224b and TTF-DEG10b were
prepared according to published literature procedures. Thin-layer
chromatography was carried out using aluminum sheets precoated
with silica gel 60 (Merck 40–60 mm, 230–400 mesh). Melting
points are uncorrected. Deuterated solvents (Cambridge Isotope
Laboratories) for NMR spectroscopic analyses were used as
received. Column chromatography was performed on silica gel 60
(Merck 40–60 nm, 230–400 mesh). Size exclusion chromatography
was performed using an Agilent 100 Series pump with a Viscotek
ViscoGEL GPC column, coupled to a Wyatt DAWN HELEOS-
II multi-angle light scattering detector and an OPTILAB rEX
refractive index detector. NMR Spectra were recorded on Varian
INOVA-400 (at 400 MHz), Varian INOVA-500 (at 500 MHz),
Varian P INOVA-500 (at 500 MHz), and Varian INOVA-600
(at 600 MHz) spectrometers. All chemical shifts are quoted
in ppm, relative to tetramethylsilane, using the residual solvent
peak as a reference standard. Mass spectra were measured on an
IonSpec 7.0T Ultima FTMS with ESI and MALDI ion sources.
Electrochemistry was performed using a Gamry Reference 600
potentiostat/galvanostat/ZRA.
3.9 ( 0.1) kcal mol-1
6 , DHo = 3.8 ( 0.1) kcal mol-1
;
23·4PF
24·nPF
6
TDSo = 2.4 ( 0.2) kcal mol-1
6 , TDSo = 2.2 ( 0.1) kcal
23·4PF
mol-1
6 ). A comparison of the thermodynamic parameters
24·nPF
from Table 1 and Table 4, also indicates that pseudorotaxane
formation is an enthalpy driven process, having a much larger
enthalpic contribution during the threading process than the
GSCC→MSCC process in the [2]catenane. This situation can be
explained by the inherent differences between a process in which
solvent molecules must be displaced from the inside of CBPQT4+
ring during pseudorotaxane formation, and circumrotation in the
catenated species, which does not require the displacement of
solvent molecules or the unraveling of the linear glycol chains of
the guest. Despite the inherent differences between the processes of
pseudorotaxane formation and circumrotation, thermodynamic
compensation ensures that the free energy (DGo) for both processes
remains closely related.
Conclusions
We have demonstrated that a reliable comparison exists between
the thermodynamic free energy differences (DDGo) observed for
the binding of different guests with modified hosts, and the
thermodynamic free energy of switching (DGo) of the analogous
bistable [2]catenanes made with the same components. A small
library of p-electron deficient CBPQT4+ hosts, modified at the
ortho positions on one of the p-xylylene rings, was synthesised,
and the consequences of the substitutions upon their binding of
p-electron rich guests were evaluated by means of ITC studies
and X-ray crystallography. A decrease in the binding constants
was observed for all guests interacting with the substituted
host CBPQT4+ ring when compared to the unsubstituted host,
CBPQT4+, as a result of the loss of a single [C–H ◊ ◊ ◊ O] interaction.
This observation was further supported by studying the linear free
energy relationships (LFERs) describing steric size for each sub-
stituent (R)—quantified by both the Winstein-Holness A values,28
and steric Taft parameters29 (Es)—and the influence of such on
the binding strength of the host and guest (Ka). However, the
behaviour of the resulting bistable catenanes is unchanged because
the interactions of the cyclophane with both recognition units are
diminished to the same extent. This behaviour was illustrated by
synthesising an alkyne-modified bistable [2]catenane, as well as a
polymer with a bistable [2]catenane side-chain modification. In
both systems, the switching thermodynamics were comparable to
the unmodified bistable [2]catenane, and the switching thermody-
namics could be predicted by inspection of the DDGo values of the
components enabling accurate predictions without cumbersome
synthesis. The additivity of the thermodynamic differences (DDGo)
observed for binding of different guests with modified hosts,
and the thermodynamic switching parameters (DGo) in MIMs is
consistent, at the very least, with the long forgotten concept34 of
the ‘parachor’, where these thermodynamic quantities, obtained
from two separate binding experiments “which are a priori
independent”, require35 the examination of their influence on the
switching behavior of the analogous MIM, and their “eventual
statistical dependence a posteriori”.
General procedure of the cyclisation to form tetracationic
cyclophane hosts
1, 1¢ - [ 1 , 4 - Phenylenebis - ( methylene ) ] bis ( 4 , 4¢ - bipyridinium)
bis(hexafluorophosphate) (1 equiv.) was added to a solution of
the appropriate dibromo-p-xylene derivative (1 equiv.) and the
template 17 (3 equiv.) dissolved in DMF. The reaction mixture was
subjected to high pressure (10–15 kbar) for three days. The solvent
was removed from the resulting purple solution under vacuum,
and the purple oil was subjected to liquid–liquid extraction
[CHCl3/1% (w/v) NH4Cl (aq)] until the solution became
colourless. The solvent was removed from the aqueous portion
and the resulting solid was subjected to column chromatography
[SiO2: MeOH/MeNO2/2 M NH4Cl (7 : 1 : 2)]. The eluent
was removed in vacuo, the solid was dissolved in hot H2O and
a saturated aqueous solution of NH4PF6 was added until no
further precipitate was observed. The precipitate was recovered
by filtration to give the appropriate tetracationic cyclophane as
its tetrakis(hexafluorophosphate) salt.
1·4PF6. (33 mg, 0.13 mmol, 10%) 1H NMR (500 MHz,
CD3CN) d = 9.28 (d, J = 6 Hz, 2 H), 9.23 (d, J = 7 Hz, 2
H), 9.08 (d, J = 7 Hz, 2 H), 8.49–8.40 (m, 6 H), 8.37 (d, J =
7 Hz, 2 H), 7.68–7.60 (m, 4 H), 7.53 (d, J = 8 Hz, 1 H), 7.49 (s,
1 H), 7.44 (d, J = 8 Hz, 1 H), 6.11 (s, 2 H), 6.04 (s, 2 H), 6.02
(s, 2 H), 2.32 (s, 3 H); 13C NMR (125 MHz, CD3CN) d = 149.8,
149.5, 145.6, 145.4, 145.3, 145.2, 139.2, 136.4, 136.2, 136.1, 134.4,
132.1, 131.9, 130.4, 130.3, 127.6, 127.3, 127.2, 127.1, 64.6, 64.5,
62.2, 18.2; ESI-HRMS: m/z calcd for C37H34F18N4P3 [M - PF6]+ =
1305.3267; found 1305.3134.
2·4PF6. (150 mg, 0.127 mmol, 18%) 1H NMR (500 MHz,
CD3CN) d = 9.47 (d, J = 7 Hz, 2 H), 9.38 (m, 4 H), 8.65 (d,
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J = 7 Hz, 2 H), 8.62 (d, J = 7 Hz, 2 H), 8.56 (d, J = 7 Hz, 2 H),
8.51 (d, J = 7 Hz, 2 H), 8.36 (d, J = 6 Hz, 2 H), 7.82–7.74 (m, 6 H),
7.71 (dd, J = 7 Hz, 2 Hz, 1 H), 7.62–7.57 (m, 3 H), 7.47–7.42 (m, 2
H), 6.25 (s, 2 H), 6.21 (s, 2 H), 6.19 (s, 2 H), 6.17 (s, 2 H); 13C NMR
(125 MHz, CD3CN) d = 149.8, 149.76, 149.7, 149.6, 149.58, 145.4,
145.2, 145.1, 143.9, 137.9, 136.4, 136.0, 133.5, 133.5, 131.9, 131.3,
130.5, 130.4, 129.5, 129.2, 129.2, 128.6, 127.4, 127.4, 127.3, 126.6,
64.6, 64.5, 64.3, 62.3; ESI-HRMS: m/z calcd for C42H36F18N4P3
[M - PF6]+ = 1367.3433; found 1367.3230.
20. A mixture of the monomer 19 (250 mg, 1.02 mmol) and
Me2CO (3 mL) were degassed in a Schlenk flask by six freeze-
pump-thaw cycles. This mixture was then injected into another
dry Schlenk flask containing CuBr (9.3 mg, 0.065 mmol) and
4,4¢-dinonyl-2,2¢-dipyridal (DNBB) (20.2 g, 0.049 mmol) and the
mixture was left to stir for 10 min. Ethyl 2-bromoisobutyrate
(EBIB) (9.5 mL, 0.065 mmol) was then injected into the reaction
mixture which was left to stir for 16 h. The reaction mixture was
diluted with CH2Cl2 then washed with saturated aqueous Na2CO3 :
EDTA mixture. The organic layer was washed with a saturated
NaCl solution, dried (MgSO4), and then precipitated into hexane.
The solvent was subsequently removed under vacuum, affording
the azide polymer 20 (conversion > 95% det. by 1H NMR
spectroscopy); Mn = 39,000; Mw = 55,000 PDI = 1.4 det. by
4·4PF6. (284 mg, 0.241 mmol, 34%) 1H NMR (500 MHz,
CD3CN) d = 8.97–8.86 (m, 8 H), 8.25–8.18 (m, 6 H), 8.15 (d,
J = 7 Hz, 2 H), 7.81 (d, J = 2 Hz, 1 H), 7.72 (d, J = 8 Hz, 1
H), 7.63 (dd, J = 2 Hz, 8 Hz, 1 H), 7.57 (s, 4 H), 5.93 (s, 2 H),
5.78 (s, 2 H), 5.77 (s, 2 H), 5.76 (s, 2 H); 13C NMR (125 MHz,
CD3CN) d = 63.6, 63.8, 64.6, 117.3, 124.8, 126.9, 127.2, 127.3,
127.4, 129.6, 130.1, 130.3, 133.4, 134.3, 134.9, 135.8, 135.9, 137.8,
145.1, 145.2, 145.7, 149.3, 149.4, 149.7; ESI-HRMS: m/z calcd for
C36H31F12N4P2 [M - 2PF6]2+ = 444.0502; found 444.0519.
GPC analysis. H NMR (CD2Cl2, 400 MHz, 25 ◦C): d = 0.86–
1
1.23 (m, 3H), 1.82–1.96 (m, 2H), 3.39 (s, 2H),◦3.64–3.67 (m, 6H),
4.08 (s, 2H); 13C NMR (CDCl3, 400 MHz, 25 C): d = 16.4, 44.6,
50.8, 63.9, 68.5, 69.9, 70.5, 177.4.
21·nPF6. A mixture of the azide polymer 20 (25.6 mg,
0.105 mmol) and CBPQT4+ alkyne derivative 7·4PF6 (124.5 g,
0.105 mmol) was added to DMF-d7 (1 mL) in a dry NMR tube
and it was degassed by bubbling Ar through the solution for 2 h. An
1H NMR spectrum of this mixture was recorded at this juncture.
CuI (20 mg, 0.105 mmol) was then added to the reaction mixture.
1
5·4PF6. (95 mg, 0.075 mmol, 25%) H NMR (500.1 MHz,
CD3CN) d = 8.87 (m, 6 H), 8.83 (d, J = 7 Hz, 2 H), 8.18 (m, 6
H), 8.11 (d, J = 7 Hz, 2 H), 7.62 (dd, J = 8 Hz, J = 1 Hz, 1 H),
7.53 (s, 4 H), 7.62 (d, J = 8 Hz, 1 H), 6.94 (s, J = 1 Hz, 1 H),
5.74 (s, 4 H), 5.70 (s, 4 H), 3.74 (s, 3 H); 13C NMR (125 MHz,
CDCl3) d = 30.7, 56, 5, 61.4, 65.5, 65.8, 112.8, 118.2, 122.9, 125.2,
127.3, 128.1, 128.2, 131.6, 131.2, 132.9, 136.8, 136.9, 138.8, 146.1,
146.7, 149.9, 150.1, 150.3, 150.4, 159.1; ESI-HRMS: m/z calcd for
C37H36F12N4OP2 [M - 2PF6]2+ = 420.1008; found 420.1007.
◦
The reaction was heated to 60 C in a sandbath and monitored
periodically with 1H NMR spectroscopy. After 24 h, the reaction
mixture was cooled and washed with aqueous EDTA. The organic
layer was then added dropwise to a saturated NH4PF6 solution in
H2O to precipitate out the product. The precipitate was recovered
by filtration to afford the 21·nPF6 copolymer as a crystalline brown
solid (145 mg, conversion > 95% by 1H NMR); Mn = 2.27 ¥ 105 g
mol-1 (det. by 1H NMR integration analysis); Mw = (1.99 0.14) ¥
106 g/mol, Mn = (1.63 0.07) ¥ 105 g mol-1, PDI = 1.5 ( 0.1) (det.
by SEC-MALS analysis). 1H NMR (DMF-d7, 500 MHz, 25 ◦C):
d = 0.78–1.32 (m), 1.66–1.81(br s), 3.51–3.80 (m), 3.92–4.03 (br
s), 4.05–4.20 (br s), 4.62–4.88 (m), 5.55–5.75 (m), 6.12–6.28 (br
m), 6.30–6.49 (br s), 7.91–8.12 (m), 8.42–8.49 (m), 8.53–8.83 (m),
9.34–9.78 (br m).
10. Compound 8 (0.50 g, 2.7 mmol), n-bromosuccinimide
(1.01 g, 5.7 mmol), and benzoyl peroxide were added to a solution
of CH2Cl2 (20 mL). The solution was stirred vigorously under
reflux for 1 day in the presence of a sodium lamp. After cooling
down to room temperature, the solution was filtered, and the
solvent was evaporated off under vacuum. Purification of the
residue by column chromatography [SiO2: MeOH : CH2Cl2 (1 :
99)] gave compound 10 as a white solid (650 mg, 1.9 mmol, 70%).
1H NMR (125 MHz, CDCl3) d = 7.53–7.40 (m, 8H), 4.53 (s, 2H),
4.44 (s, 2H); 13C NMR (125 MHz, CDCl3) d = 31.5, 32.6, 121.7,
128.3, 128.49, 128.8, 130.9, 131.4, 135.3, 137.9, 139.5, 142.4; ESI-
HRMS: m/z calcd for C14H12Br2 = 338.9208; found = 338.9196.
23·4PF6. The dicationic building block 16·2PF6 (204 mg,
0.289 mmol) was added to a solution of the dibromide 15 (100 mg,
0.289 mmol) and macrocycle 22 (100 mg, 0.135 mmol) dissolved
in dry DMF (50 mL). The reaction mixture was stirred for 1 week.
The solvent was removed from the resulting green solution under
vacuum, and the green solid was redissolved in Me2CO. The
solution was subjected to column chromatography (SiO2), first
eluting the yellow band containing unreacted macrocycle 22 using
Me2CO and then changing to [MeOH/MeNO2/H2O/2M NH4Cl
(7 : 1 : 2)]. The eluent was removed under vacuum, the solid
was dissolved in hot H2O, and a saturated aqueous solution of
NH4PF6 was added until no further precipitate was observed. The
precipitate was recovered by filtration to afford 23·4PF6 (101 mg,
0.052 mmol, 39%) as a green solid. 1H NMR (CD3CN, 400 MHz,
19. 2-(2-(2-Azidoethoxy)ethoxy)ethanol (18) (7.0 g, 40 mmol)
and Et3N (4.0 g, 39.5 mmol) were added to dry degassed CH2Cl2
(175 mL) and the mixture was left to stir for 1 h. The reaction
mixture was cooled down to 0 ◦C and methacryloyl chloride
(4.80 g, 46.3 mmol) was added. The reaction was warmed up
slowly to 25 ◦C and stirred for a further 14 h. The solvent was
removed under vacuum, and the resulting mixture was subjected
to column chromatography [SiO2: CH2Cl2 : hexane (6.5 : 3.5)]. The
fractions containing the product were combined and solvent was
removed in vacuo to give 19 as a colourless oil (7.7 g, 32 mmol,
68%). 1H NMR (CDCl3, 400 MHz, 25 ◦C): d = 1.89–1.90 (dd, J =
1.43 Hz, 3H), 3.33 (t, J = 4.91 Hz, 2H), 3.59–3.65 (m, 6H), 3.70
(t, J = 4.92 Hz, 2H), 4.25 (t, J = 4.93 Hz, 2H), 5.52–5.53 (m, 1H),
6.07–6.08 (m, 1H); 13C NMR (CDCl3, 400 MHz, 25 ◦C): d = 18.3,
50.7, 63.8, 69.0, 69.2, 70.1, 125.7, 136.1, 167.3; ESI-HRMS: m/z
calcd for C10H17N3O4 = 243.121; found: 244.128 [M + H]+.
◦
25 C): d = 3.02 (s, 1H), 3.50–4.16 (m, 36H), 5.08 (s, 2H), 5.67
(s, 4H), 5.84 (s, 2H), 5.96 (s, 2H), 6.06 (br s, 2H), 6.69–6.78 (m,
2H), 7.23–7.34 (br s, 4H), 7.38–7.426 (br s, 3 H), 7.57–7.70 (m, 8H),
7.73–7.88 (m, 3H), 8.30–8.42 (s, 1H), 8.54–9.29 (m, 8H); 13C NMR
(CD3CN, 400 MHz, 25 ◦C): d = 22.7, 28.6, 33.7, 34.5, 38.5, 40.4,
56.7, 61.9, 64.1, 64.6, 64.8, 64.9, 68.0, 68.3, 69.8, 70.0, 70.2, 70.6,
4402 | Org. Biomol. Chem., 2009, 7, 4391–4405
This journal is
The Royal Society of Chemistry 2009
©

70.7, 70.8, 71.1, 71.2, 71.5, 106.1, 107.8, 108.0, 114.1, 125.7, 126.3,
130.1, 131.2, 132.8, 134.9, 135.9, 136.6, 144.7, 144.9, 145.2, 154.1,
173.6.; ESI-HRMS: m/z calcd for C74H78O12N4P4S4F24: 1922.31;
found: 1777.340 [M - PF6]3+, 816.292 [M - 2PF6]2+, 495.843 [M -
3PF6]+, 743.276 [M - 2PF6 - HPF6]2+.
X-Ray crystal data
23·4PF6. The X-ray crystal data for compound 23·4PF6 was
collected at 173 K using a Rigaku MM007 High brilliance RA
generator (Cu-Ka radiation) equipped with confocal optics and
Saturn92 CCD system. The results were obtained after collecting
data for many crystals from different crystallisation attempts.
All of the crystals examined gave the same unit cell and crystal
system; the data reported here is the most well behaved. Intensities
were corrected for Lorentz-polarization and for absorption. The
structure was solved by direct methods. Hydrogen atoms bound
to carbon were idealised. Structural refinements were obtained
with full-matrix least-squares based on F2 by using the program
SHELXTL.27 CCDC 720651 contains the supplementary crystal-
lographic data for this compound.†
24·nPF6. A mixture of the azide polymer 20 (30 mg,
0.123 mmol) and 23·4PF6 (63 mg, 0.033 mmol) was added to
DMF-d7 (1 mL) in a dry NMR tube and it was degassed by
bubbling Ar through the solution for 2 h. An 1H NMR spectrum
of this mixture was taken at this point. CuI (15 mg, 0.079 mmol)
was added to the reaction mixture. The reaction mixture was then
heated to 60 ◦C in a sandbath for 24 h, and followed periodically
by NMR spectroscopy. Excess of methyl propargyl ether was then
injected into the reaction mixture, and heated for an additional
24 h at 60 ◦C. The reaction mixture was cooled and washed with
aqueous EDTA. The organic layer was then added dropwise to
a saturated NH4PF6 solution in MeOH to precipitate out the
product. The precipitate was recovered by filtration to afford the
side-chain poly[2]catenane 24·nPF6 as a crystalline green solid
(90 mg, conversion > 95% det. by 1H NMR spectroscopy); Mn =
1.28 ¥ 105 g mol-1 (det. by 1H NMR integration analysis); Mw =
(1.3 0.07) ¥ 106 g mol-1, Mn = (8.7 0.61) ¥ 105 g mol-1, PDI
Crystal data for 23·4PF6. C74H78F24N4O12P4S4.6.5H2O.C6H14O,
M = 2142.80, space group P21/c, monoclinic, a = 14.216(4), b =
◦
3
˚
˚
54.971(12), c = 13.678(4) A, b = 109.254(7) , U = 10091(4) A ,
Z = 4, m = 2.427 mm-1, 126248 reflections collected, 11023
observed independent reflections (Rint 0.0854) gave R 0.1969 for
I > 2s(I) and wR(F2) was 0.5261.
DNP-DEGÃ1·4PF6 and TTFÃ1·4PF6. The X-ray crystal data
for DNP-DEGÃ1·4PF6 and TTFÃ1·4PF6 were collected with a
Bruker Smart 1000 CCD-based X-ray diffractometer. The frames
for the data collection were integrated with the Bruker SAINT
program system using a narrow-frame integration algorithm. The
superstructures were solved by direct methods and refined based
on F2 using the SHELXTL software package.36 CCDC 720652–
720653 contain the supplementary crystallographic data for these
compounds.†
1
=1.5 ( 0.1) (det. by SEC-MALS analysis). H NMR (DMF-d7,
500 MHz, 25 ◦C): d = 0.80–1.37 (m), 1.72–2.19 (m), 3.24–4.89
(m), 5.56–5.85 (br s), 5.89–6.27 (m), 6.32–6.57 (br s), 6.75–6.89 (br
s), 7.23–7.37 (br s), 7.37–7.47 (br s), 7.69–8.14 (m), 8.20–8.75 (m),
9.12–9.74 (m).
Crystal data for DNP-DEGÃ1·4PF6. C67H76N10O6](PF6)4, M =
Isothermal titration microcalorimetry
1697.26, space group P21/n, monoclinic, a = 13.8934(9),
◦
˚
b = 23.2237(16), c = 13.0531(9) A, b = 116.2620(10) , V =
Microcalorimetry was carried out using a Microcal VP-ITC titra-
tion microcalorimeter. Aliquouts (3–7 mL) of degassed solutions of
the guest in MeCN were titrated with stirring into solutions of the
host at 298 K. The heat of dilution for each titration was measured
by determining the heat released on the injection of the guest
into MeCN in the absence of host, and the enthalpy of dilution
was subtracted from the enthalpy of the titration to determine
the enthalpy of complexation. Software provided by Microcal
LLC was used to compute the thermodynamic parameters of the
titration (DGo, Ka, DSo, DHo) based on the one-site binding model.
The reported values in Table 1 are the mean results of multiple
titrations, and errors are reported as a standard deviation from
the mean.
3776.9(4) A , Z = 2, Dcalcd. = 1.492 g cm-3, m(Mo-Ka) = 0.216 mm-1,
3
˚
T = 120(2) K, red prisms, 9064 independent measured reflections,
5614 independent observed reflections [|Fo| > 4s(|Fo|), 2qmax
54◦], F2 refinement, R1 = 0.061, wR2 = 0.139, 538 parameters.
=
Crystal data for TTFÃ1·4PF6. C43H38N4S4](PF6)4.1.8(C2H3N)
M = 1392.79, space group P21/n, monoclinic, a = 10.8498(8),
◦
˚
b = 19.3989(14), c = 13.8729(10) A, b = 106.5760(10) , V =
2798.5(4) A , Z = 2, Dcalcd. = 1.653 g cm-3, m(Mo-Ka) = 0.406 mm-1,
3
˚
T = 120(2) K, green block, 6723 independent measured reflections,
4363 independent observed reflections [|Fo| > 4s(|Fo|), 2qmax
56◦], F2 refinement, R1 = 0.052, wR2 = 0.137, 436 parameters.
=
Acknowledgements
This material is based upon work supported by the National
Science Foundation under CHE-0924620. L. F. gratefully ac-
knowledges the support of a Ryan Fellowship from Northwestern
University. A. B. B. gratefully acknowledges the support of a NIH
Postdoctoral Fellowship (F32CA136148-02).
Cyclic voltammetry
Electrochemical experiments were carried out at room termpera-
ture in argon-purged solutions of MeCN, with a Gamry Reference
600 potentiostat/galvanostat/ZRA interfaced to a PC. Cyclic
voltammetric experiments were perfomed by using a glassy
carbon working electrode (0.07 cm2); its surface was polished
routinely with 0.05 mm of alumina–water slurry on a felt surface
immediately before each run. The counter electrode was a Pt
wire and the reference electrode was a Ag/AgCl electrode.
Tetrabutylammonium hexafluorophosphate (0.1 M) was added
as a supporting electrolyte.
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