Catalysis in the Self-Assembly of [2]Rotaxanes and [2]Pseudorotaxanes. Effect of the Length of Polyethereal Side Arms and Terminal Stoppers

Article abstract of DOI:10.1021/jo035483e

The template effects exerted by compounds 3, 5, 6, and 8 in the ring closure reaction of the trication 1³⁺ to yield the [2] pseudorotaxanes 15⁴⁺ and 17⁴⁺ and the [2]rotaxanes 18 ⁴⁺ and 20⁴⁺ have been quantitatively evaluated in acetonitrile at 62 °C by UV/vis spectrophotometry. The rate of ring closure of the trication 1³⁺ largely increases in the presence of the templates up to a maximum of ca. 200 times in the case of 5 at a concentration of ca. 0.08 M. The results indicate that, in the self-assembly of a rotaxane, the template effect of the guest is lowered by the presence of two large stoppers (triisopropylsilyl) at the end of the linear chains; this effect is more important the shorter the chain and can be mainly ascribed to steric effects. Previously hypothesized entropic effects appear to be of lesser importance.

Full text of DOI:10.1021/jo035483e

gated the template effect exerted by guests 4 and 7 in
the ring closure reaction of the trication 13+, which is the
acyclic precursor of cyclobis(paraquat-p-phenylene) 24+
(Scheme 1).4 The results indicated that the two bulky
triisopropylsilyl (TIPS) groups at the end of the poly-
ethereal chains, which are of course a prerequisite for
obtaining a stable rotaxane, do significantly lower the
template ability of guest 7 with respect to guest 4, which
is devoid of terminal stoppers. This finding was rational-
ized taking into account both a destabilizing steric effect,
which is enthalpic in nature, and a more subtle entropic
effect due to the different moments of inertia of the side
chains in 4 and 7. However, we were unable to indicate
which of the two effects is more important. To establish
the relative importance of the two effects, we have
changed the length of the side arms by taking into
account guests 3 and 6, and guests 5 and 8, whose side
arms are, respectively, shortened and lengthened by one
oxyethylene unit. The study of the template effects of
these guests in the cyclization of 13+ is reported here.
Ca ta lysis in th e Self-Assem bly of
[2]Rota xa n es a n d [2]P seu d or ota xa n es.
Effect of th e Len gth of P olyeth er ea l Sid e
Ar m s a n d Ter m in a l Stop p er s
Claudio D’Acerno,† Giancarlo Doddi,*,†
Gianfranco Ercolani,*,‡ Silvia Franconeri,†
Paolo Mencarelli,*,† and Alessio Piermattei†
Dipartimento di Chimica e CNR-IMC, Universita` di Roma
La Sapienza, P.le Aldo Moro 2, 00185 Roma, Italy, and
Dipartimento di Scienze e Tecnologie Chimiche, Universita`
di Roma Tor Vergata, Via della Ricerca Scientifica,
00133 Roma, Italy
giancarlo.doddi@uniroma1.it; ercolani@uniroma2.it;
paolo.mencarelli@uniroma1.it
Received October 9, 2003
Abstr a ct: The template effects exerted by compounds 3,
5, 6, and 8 in the ring closure reaction of the trication 13+
to yield the [2]pseudorotaxanes 154+ and 174+ and the [2]-
rotaxanes 184+ and 204+ have been quantitatively evaluated
in acetonitrile at 62 °C by UV/vis spectrophotometry. The
rate of ring closure of the trication 13+ largely increases in
the presence of the templates up to a maximum of ca. 200
times in the case of 5 at a concentration of ca. 0.08 M. The
results indicate that, in the self-assembly of a rotaxane, the
template effect of the guest is lowered by the presence of
two large stoppers (triisopropylsilyl) at the end of the linear
chains; this effect is more important the shorter the chain
and can be mainly ascribed to steric effects. Previously
hypothesized entropic effects appear to be of lesser impor-
tance.
Resu lts a n d Discu ssion
The first-order rate constant (k0 ) 8.3 × 10-7 s-1) for
the cyclization of the trication 13+, in the absence of any
added template, to yield cyclobis(paraquat-p-phenylene)
1
2
4+ was previously obtained by H NMR in CD3CN at 62
°C.5 First-order rate constants (kobs) in acetonitrile at 62
°C have been obtained in the presence of variable excess
amounts of the polyether templates 3-8 (up to ∼0.08 M)
by following the kinetics of formation of either pseudoro-
taxanes or rotaxanes 154+-204+. These compounds present
a charge-transfer band at λ 520 nm,6 which has been
exploited to study the kinetics by UV/vis spectroscopy.
In tr od u ction
(2) For general reviews on template effects, see: (a) Anderson, S.;
Anderson, H. L.; Sanders, J . K. M. Acc. Chem. Res. 1993, 26, 469-
475. (b) Hoss, R.; Vo¨gtle, F. Angew. Chem., Int. Ed. Engl. 1994, 33,
375-384. (c) Busch, D. H.; Vance, A. L.; Kolchinski, A. G. In
Comprehensive Supramolecular Chemistry; Atwood, J . L., Davies, J .
E. D., MacNicol, D. D., Vo¨gtle, F., Sauvage, J .-P., Hosseini, M. W.,
Eds.; Pergamon: Oxford, 1996; Vol. 9, Chapter 1. (d) Gerbeleu, N. V.;
Arion, V. B.; Burgess, J . Template Synthesis of Macrocyclic Compounds;
Wiley-VCH: Weinheim, Germany, 1999. (e) Templated Organic Syn-
thesis; Diederich, F., Stang, P. J ., Eds.; Wiley-VCH: Weinheim,
Germany, 2000.
The design and creation of machine-like molecular
assemblies has attracted considerable attention in recent
years because of potential applications in the field of
information processing and technology.1 Many such as-
semblies have as a distinctive structural feature one or
more macrocycles threaded by a linear component whose
unthreading is either fully reversible (pseudorotaxanes)
or prevented by the presence of large stoppers at the ends
of the chain (rotaxanes). The efficient preparation of these
interesting supramolecular structures has enormously
benefited from template-directed approaches.2,3 However,
despite the abundance of preparative reports and the
general interest in the subject of templated synthesis,
the kinetic study of template effects in the formation of
rotaxanes lagged behind.
(3) For reviews on template-directed syntheses of rotaxanes, see:
(a) Amabilino, D. B.; Stoddart, J . F. Chem. Rev. 1995, 95, 2725-2828.
(b) Belohradsky, M.; Raymo, F. M.; Stoddart, J . F. Collect. Czech. Chem.
Commun. 1996, 61, 1-43. (c) Amabilino, D. B.; Raymo, F. M.; Stoddart,
J . F. In Comprehensive Supramolecular Chemistry; Atwood, J . L.;
Davies, J . E. D., MacNicol, D. D., Vo¨gtle, F., Sauvage, J .-P., Hosseini,
M. W., Eds.; Pergamon: Oxford, 1996; Vol. 9, Chapter 3. (d) Gibson,
H. W. In Large Ring Molecules; Semlyen, J . A., Ed.; Wiley: New York,
1996; pp 191-262. (e) Philp, D.; Stoddart, J . F. Angew. Chem., Int.
Ed. Engl. 1996, 35, 1154-1196. (f) Molecular Catenanes, Rotaxanes
and Knots; Sauvage, J .-P., Dietrich-Buchecker, C. O., Eds.; Wiley-
VCH: Weinheim, Germany, 1999. (g) Bruce, J . I.; Sauvage, J .-P. Adv.
Mol. Struct. Res. 1999, 5, 153-187. (h) Blanco, M. J .; J imenez, M. C.;
Chambron, J . C.; Heitz, V.; Linke, M.; Sauvage, J .-P. Chem. Soc. Rev.
1999, 28, 293-305. (i) Gibson, H. W.; Mahan, E. J . In Cyclic Polymers,
2nd ed.; Semlyen, J . A., Ed.; Kluwer: Dordrecht, The Netherlands,
2000; pp 415-560.
With the aim at evaluating the role played by large
stoppers in the linear component, we recently investi-
† Universita` di Roma La Sapienza.
‡ Universita` di Roma Tor Vergata.
(1) (a) Acc. Chem. Res. 2001, 34, 409-522 (Molecular Machines
Special Issue). (b) Molecular Machines and Motors; Sauvage, J .-P., Ed.;
Structure And Bonding, Vol. 99; Springer: Berlin, 2001. (c) Molecular
Switches; Feringa, B. L., Ed.; Wiley-VCH: Weinheim, Germany, 2001.
(d) Balzani, V.; Credi, A.; Venturi, M. Molecular Devices and Machiness
A J ourney into the Nano World; Wiley-VCH: Weinheim, Germany,
2003.
(4) Doddi, G.; Ercolani, G.; Franconeri, S.; Mencarelli, P. J . Org.
Chem. 2001, 66, 4950-4953.
(5) Capobianchi, S.; Doddi, G.; Ercolani, G.; Keyes, J . W.; Mencarelli,
P. J . Org. Chem. 1997, 62, 7015-7017.
(6) Ballardini, R.; Balzani, V.; Gandolfi, M. T.; Prodi, L.; Venturi,
M.; Philp, D.; Ricketts, H. G.; Stoddart, J . F. Angew. Chem., Int. Ed.
Engl. 1993, 32, 1301.
10.1021/jo035483e CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/13/2004
J . Org. Chem. 2004, 69, 1393-1396
1393

SCHEME 1
F IGURE 1. Rate enhancement produced by templates 3 (0),
4 (O), and 5 (4) on the ring closure reaction of the trication
1
3+. The points are experimental, and the curves are calculated
(see the text).
To avoid polymerization reactions, the concentration of
the substrate 13+ has been kept as low as possible (∼3-5
× 10-4 M). The ratios kobs/k0 for templates 3 and 5 and 6
and 8 are plotted in Figures 1 and 2, respectively, against
their concentrations. Such ratios provide a measure of
the rate enhancements produced by the presence of the
templates. For the sake of comparison, the previously
published data relative to templates 4 and 74 are also
reported in the corresponding figure.
F IGURE 2. Rate enhancement produced by templates 6 (0),
7 (O), and 8 (4) on the ring closure reaction of the trication
1
3+. The points are experimental, and the curves are calculated
(see the text).
The data in Figures 1 and 2 show that the ring closure
of the trication 13+ is significantly accelerated by the
presence of templates 3-8 up to a maximum of ca. 200
times in the case of 5 at a concentration of ca. 0.08 M.
However, before commenting upon these rate increases,
it is useful to go deep into the analysis of the kinetic data.
Consider the kinetic scheme illustrated in Scheme 1.
Assuming that the equilibrium of formation of complexes
93+-143+ is fast with respect to the ring closure reaction,
the rate increase produced by the template, kobs / k0, is
given by eq 1.7 Since the concentration of template is in
large excess with respect to that of the substrate, in fact
its analytical concentration can be substituted for its
actual concentration in eq 1. The constants KT# ()kcatKsub
k0) and Ksub are the association constants of the template
with the cyclic transition state and with the open chain
precursor 13+, respectively. Catalysis will be observed
when the template binds the transition state more
strongly than the reactants.8,9 On increasing the template
concentration, the ratio kobs/k0 tends to a plateau value
/
(7) D’Acerno, C.; Doddi, G.; Ercolani, G.; Mencarelli, P. Chem.sEur.
J . 2000, 6, 3540-3546.
kobs
k0
1 + KT#[template]
1 + Ksub[template]
(8) Cacciapaglia, R.; Mandolini, L. Chem. Soc. Rev. 1993, 22, 221-
)
(1)
231.
(9) Kraut, J . Science 1988, 242, 533-540.
1394 J . Org. Chem., Vol. 69, No. 4, 2004

TABLE 1. Associa tion Con sta n ts in CH3CN a t 62 °C
smaller for the longest one (5/8 pair) where the KT# value
is only halved. These results confirm our previous finding
that the two bulky TIPS groups reduce the template
ability of the guest,4 but underscore the fact that this
effect is greater the shorter the chain. It is known that
two structural features are required for optimum com-
plexation of a guest molecule by cyclobis(paraquat-p-
phenylene), namely, an aromatic core, which is essential
in placing the guest in the host cavity mainly by π-π
stacking interactions,10 and two side arms with suitably
placed oxygen atoms that interact with the acidic
R-hydrogens of the pyridinium rings of the host by
[C-H‚‚‚O] hydrogen bonding.11 The latter interactions
should be the most affected by the steric hindrance of
the two TIPS stoppers. In our previous paper we sug-
gested that also entropic effects could play a significant
role.4 Indeed the interaction between the oxygen atoms
of the side arms and the pyridinium R-protons restricts
the conformational motion of the polyethereal chains with
a consequent entropy loss. The entropy associated with
internal rotations depends not only on potential energy
barriers but also on the reduced moments of inertia of
the rotating groups.12 An increase of the reduced mo-
ments of inertia has the effect of decreasing the spacing
between the energy levels of internal rotations, and thus
of increasing the conformational entropy at temperatures
above absolute zero. The two heavy TIPS groups placed
at the end of the side arms increase the conformational
entropy of the chain, and thus, restriction of conforma-
tional motion of the side arms upon binding occurs with
a greater entropy loss. Now we are in a position to say
which of the two effects is more important. Indeed
increasing the length of the side arms and placing the
heavy TIPS groups at the end of them has the effect of
increasing the moment of inertia associated with internal
rotations involving an increase of conformational entropy.
On the contrary, steric effects exerted by the bulky TIPS
groups are more important the shorter the chain. In other
words if entropic effects were dominant, we should expect
that the ratio KT#(H)/KT#(TIPS) increases on increasing
the chain length, whereas if steric effects were dominant,
we should expect the contrary. The results point out that
steric effects are more important than entropic effects.
Assuming that steric effects are negligible in the reaction
in the presence of guest 8, we can estimate that the
entropic effects due to the different masses of end groups
should not account for more than a factor of 2.
template
Ksub, M-1
KT#, M-1
KT#/Ksub
3
8 ( 2
11 ( 2
6 ( 1
2900 ( 200
3000 ( 210
3450 ( 100
59 ( 15
360 ( 70
273 ( 30
627 ( 50
4a
5
6
7a
8
7 ( 2
7 ( 1
850 ( 80
121 ( 23
256 ( 19
1790 ( 70
a
Reference 4.
given by the ratio KT#/Ksub. If however the product Ksub
[template] is ,1 even at the maximum template concen-
tration, eq 1 reduces to the linear form of eq 2 in which
the tendency to saturation disappears.
kobs
) 1 + KT#[template]
(2)
k0
All the curves in Figures 1 and 2 with the exception of
that relative to guest 6 show a clear tendency to satura-
tion; thus, the values of kobs/ k0 have been fitted to eq 1,
except in the case of 6, where they have been fitted to eq
2. The association constants obtained from the fitting
procedure are reported in Table 1; they have been used
to calculate the curves in Figures 1 and 2 by eq 1 or, in
the case of 6, by eq 2.
The saturation value, KT#/Ksub, is the maximum theo-
retical rate enhancement which would be attained when
the substrate is completely bound to the template. The
corresponding values, reported in Table 1, indicate that
the complexed forms of 13+ are more reactive than the
free one. The enhancements range from ∼30 times for
guest 6 (this very approximate value has been estimated
by assuming Ksub[template] ≈ 0.1, from which Ksub ≈ 2
M-1) to ∼600 times for guest 5. Such rate enhancements
are due to the fact that the associations of the acyclic
trication 13+ with all the templates are rather weak
whereas the cyclic transition state shows a much greater
ligand affinity toward them. This is mainly due to the
preorganization of the cyclic transition state and, sec-
ondarily, to the development of a further positive charge
on the initially neutral nitrogen atom.
Upon inspection of Table 1 and Figure 1, it is apparent
that guests 3-5, which are devoid of terminal stoppers
and which give rise to the formation of pseudorotaxanes,
have similar catalytic effects. Indeed the increase of the
length of the side arms beyond the two oxyethylene units
of 3 involves only modest variations, with a non clearly
recognizable trend, of both the values of Ksub and KT#.
The behaviors of guests 6-8 giving rise to the formation
of rotaxanes and illustrated in Figure 2 are, in contrast,
much more differentiated. In this case there is a clear
trend showing that catalysis increases on increasing the
length of the side arms. Comparing the results for the
pairs 3/6, 4/7, and 5/8, having the same number of
oxygens along the polyethereal chains but differing for
the nature of the end groups, it appears that substitution
of the TIPS groups for the terminal hydrogens involves
a significant lowering of catalysis that can be mainly
ascribed to the lower values of the KT# constants. This
effect is clearly dependent on the side chain length: it is
dramatic for the shortest one (3/6 pair) where the KT#
value is reduced from 2900 to 59 M-1, whereas it is much
In conclusion the results here presented indicate that,
in the self-assembly of a rotaxane, the template effect of
the guest is lowered by the presence of two large stoppers
at the end of the linear chains; this effect is more
important the shorter the chain and can be mainly
ascribed to steric effects.
Exp er im en ta l Section
Ma ter ia ls a n d Meth od s. 1,1′′-[1,4-Phenylenebis(methyl-
ene)]-1′-(4-(bromomethyl)benzyl)-bis(4,4′-bipyridinium) tris(hexa-
fluorophosphate) (13+‚3PF6-) was from our previous work.4
(10) Ercolani, G.; Mencarelli, P. J . Org. Chem. 2003, 68, 6472-6473.
(11) Houk, K. N.; Menzer, S.; Newton, S. P.; Raymo, F. M.; Stoddart,
J . F.; Williams, D. J . J . Am. Chem. Soc. 1999, 121, 1479-1487.
(12) Ercolani, G. J . Org. Chem. 1999, 64, 3350-3353 and references
therein.
J . Org. Chem, Vol. 69, No. 4, 2004 1395

The compounds 3,13 5,14 and 615 were prepared according to
literature procedures.
HPLC grade acetonitrile was used in the kinetic experiments
without further purification. Kinetic measurements were carried
out on a UV-vis spectrophotometer.
Kin etic Mea su r em en ts. Kinetic measurements were carried
out, at 62 °C, in acetonitrile, in a 3 mL cuvette (optical path 1
cm) kept in the thermostated cell compartment of the spectro-
1,5-Bis[2-[2-[2-[2-(triisopropylsilyloxy)ethoxy]ethoxy]ethoxy]-
ethoxy]naphthalene (8) was prepared by following the procedure
reported for the simpler homologue 7:15 Triisopropylsilyl triflate
(1.53 g, 4.9 mmol) in dry CH2Cl2 (20 mL) was added to a solution
of 5 (1.0 g, 1.96 mmol) and 2,6-dimethylpyridine (0.52 g, 4.9
mmol) in dry CH2Cl2 (30 mL) under N2. After the mixture was
stirred at room temperature overnight, the organic layer was
washed with H2O and dried (Na2SO4). The solvent was removed
under reduced pressure, and the residue was purified by column
chromatography (SiO2, CH2Cl2/CH3OH, 95/5) to afford 8 as a
pale oil (1.24 g, 77%). ES-MS: m/z ) 843.0 (M + NH4)+, 848.0
photometer. In a typical run, 100 µL of a 0.010 M solution of
-
1
3+‚3PF6 was added to a 2.5 mL solution of the template 3, 5,
6, or 8 at the appropriate concentration (see below). The
appearance of the charge-transfer band of 154+, 174+, 184+, or
204+ was followed at λ 520 nm. In all of the cases a clean first-
order behavior was observed. Relative kinetic constants (kobs
/
k0, where k0 ) 8.3 × 10-7 s-1) at the various template concen-
trations (corrected for the volume increase at 62 °C and given
in parentheses in M) were as follows: (template 3) 1 (0), 48.8
(2.00 × 10-2), 80.7 (3.65 × 10-2), 101.9 (4.42 × 10-2), 106.4 (5.15
× 10-2), 136.1 (7.48 × 10-2); (template 5) 1 (0), 51.8 (1.62 × 10-2),
52.4 (1.65 × 10-2), 92.8 (3.07 × 10-2), 137.4 (4.98 × 10-2), 162.4
(6.51 × 10-2), 194.0 (7.97 × 10-2); data plotted in Figure 1;
(template 6) 1 (0), 2.2 (2.00 × 10-2), 2.62 (3.00 × 10-2), 4.08 (4.83
× 10-2), 5.40 (5.50 × 10-2), 3.53 (6.02 × 10-2); (template 8) 1
(0), 26.8 (1.51 × 10-2), 48.0 (3.16 × 10-2), 66.4 (5.00 × 10-2),
81.3 (6.53 × 10-2), 95.1 (8.00 × 10-2); data plotted in Figure 2.
1
(M + Na)+. H NMR (300 MHz, CDCl3, 25 °C): δ 1.05-1.08 (42
H, m), 3.57-3.86 (24 H, m), 4.00 (4 H, m), 4.29 (4 H, m), 6.84 (2
H, d, J ) 8 Hz), 7.35 (2 H, t, J ) 8 Hz), 7.87 (2 H, d, J ) 8 Hz).
Anal. Calcd for C44H80O10Si2: C, 64.04; H, 9.77. Found: C, 63.65;
H, 9.42.
(13) Brown, C. L.; Philp, D.; Spencer, N.; Stoddart, J . F. Isr. J . Chem.
1992, 32, 61-67.
(14) Ashton, P. R.; Huff, J .; Menzer, S.; Parsons, I. W.; Preece, J .
A.; Stoddart, J . F.; Tolley, M. S.; White, A. J . P.; Williams, D. J . Chem.s
Eur. J . 1996, 2, 31-44.
(15) Bravo, J . A.; Raymo, F. M.; Stoddart, J . F.; White, A. J . P.;
Williams, D. J . Eur. J . Org. Chem. 1998, 2565-2571.
J O035483E
1396 J . Org. Chem., Vol. 69, No. 4, 2004