Cooperative self-assembly of dendrimers via pseudorotaxane formation from a homotritopic guest molecule and complementary monotopic host dendrons

Article abstract of DOI:10.1021/ja012155s

Interaction of the homotritopic guest 1,3,5-tris[p-(benzylammoniomethyl)phenyl]benzene tris- (hexafluorophosphate) (1a) with dibenzo-24-crown-8 (DB24C8) leads to the sequential self-assembly of [2]-, [3]-, and [4]-pseudorotaxanes 7a, 8a, and 9a, respectiv

Full text of DOI:10.1021/ja012155s

Published on Web 04/02/2002
Cooperative Self-Assembly of Dendrimers via Pseudorotaxane
Formation from a Homotritopic Guest Molecule and
Complementary Monotopic Host Dendrons
Harry W. Gibson,* Nori Yamaguchi, Lesley Hamilton, and Jason W. Jones
Contribution from the Department of Chemistry, Virginia Polytechnic Institute &
State UniVersity, Blacksburg, Virginia 24061
Received September 10, 2001. Revised Manuscript Received October 8, 2001
Abstract: Interaction of the homotritopic guest 1,3,5-tris[p-(benzylammoniomethyl)phenyl]benzene tris-
(hexafluorophosphate) (1a) with dibenzo-24-crown-8 (DB24C8) leads to the sequential self-assembly of
[2]-, [3]-, and [4]-pseudorotaxanes 7a, 8a, and 9a, respectively. The self-assembly processes were studied
using NMR spectroscopy. In CD3CN and CD3COCD3 the individual association constants K1, K2, and K3
+
for 1:1, 1:2, and 1:3 complexes were determined by several methods. Via Scatchard plots, the three NH2
sites of 1a were shown to behave independently in binding DB24C8. K values (4.4 × 102, 1.4 × 102, and
41 M-1, respectively, in CD3CN) directly determined from signals for the individual complexes (7a, 8a, and
9a) were somewhat higher than those estimated from the Scatchard plot because of concentration
dependence, but the ratios of association constants followed the expected statistical order (K1:K2:K3
)
3:1:1/3). These are believed to be the first evaluations of association constants leading to a [4]-pseudoro-
taxane. In the less polar CDCl3, association constants could not be determined because ∼90% of the
dissolved tritopic guest, which by itself is insoluble, was present as the fully loaded [4]pseudorotaxane 9a!
Self-assembly of homotritopic guest 1a with benzyl ether dendrons of the first, second, and third generations
functionalized at the “focal point” with DB24C8 moieties (3-5) produces pseudorotaxane dendrimers. The
self-assembly processes were studied using 1H NMR spectroscopy. In CD3COCD3 for all three generations
the individual association constants K1, K2, and K3 for [2]-, [3]-, and [4]-pseudorotaxane complexes 7c-e,
8c-e, and 9c-e indicated that the self-assembly was cooperative; that is, the ratios of the individual
association constants exceeded the expected statistical ratios. Scatchard plots confirmed this behavior.
Self-assembly processes in the less polar CDCl3 were kinetically slow, requiring ca. 1, 2, and 3 days,
respectively, for the first, second, and third generation systems to reach equilibrium with 1a; the slow rate
is attributed to the insolubility of the homotritopic guest 1a in this medium and the steric demands of the
resulting dendrimers. However, only dendrimers of 1:3 stoichiometry, that is, the nanoscopic [4]-
pseudorotaxanes 9, were formed! Moreover, it is noteworthy that the extent of dissolution of 1a (reflective
of the overall association constant which is too high to measure) increases with generation number,
presumably because of the more effective screening of the ionic guest by the larger dendrons and perhaps
favorable π-π and CH-π interactions. Such cooperative effects suggest a number of applications that
can take advantage of the pH-switchable nature of these self-assembly processes.
delivery,7 sensors/diagnostics,8 and membrane chemistry.9 How-
ever, structural control and synthetic efficiency still remain major
Introduction
Supramolecular chemistry has developed rapidly as scientists
around the world endeavor to produce nanoscopically controlled
multicomponent structures with designed functionality.1 Pseu-
dorotaxanes and rotaxanes,2 mechanically linked molecular com-
pounds in which a cyclic molecule is threaded by a linear mole-
cule, are an important subset of such self-assembled structures.
Dendrimers with their large and controllable numbers of end
groups, unique shapes, and physical properties provide an almost
endless array of possibilities for design of materials with targeted
end-use functionalities.3 Thus, dendrimers are beginning to find
potential applications in the fields of photo- and electroactive
materials,4 bioactive agents,5 catalysis,6 encapsulation and
issues in dendrimer research.10 Three methods (convergent,11
divergent,12 and double-stage convergent13) are recognized for
high molecular weight, monodisperse dendrimer synthesis.
(1) Vo¨gtle, F. Supramolecular Chemistry; John Wiley and Sons: New York,
1991. Cram, D. J.; Cram, J. M. Container Molecules and Their Guests;
Royal Society of Chemistry: Cambridge, U.K., 1994. Lehn, J.-M. Supra-
molecular Chemistry; VCH Publishers: New York, 1995. ComprehensiVe
Supramolecular Chemistry; Atwood, J. L., Davies, J. E. D., MacNicol, D.
D., Vo¨gtle, F., Eds.; Pergamon Press: New York, 1996. Moore, J. S. Curr.
Opin. Colloid Interface Sci. 1999, 4, 108-116. Caulder, D. L.; Raymond,
K. N. Acc. Chem. Res. 1999, 32, 975-982. Rowan, A. E.; Elemans, J. A.
A. W.; Nolte, R. J. M. Acc. Chem. Res. 1999, 32, 995-1006. Leininger,
S.; Olenyuk, B.; Stang, P. J. Chem. ReV. 2000, 100, 853-908. Self-Assembly
in Supramolecular Systems; Lindoy, L. F., Atkinson, I. M., Eds.; Royal
Society of Chemistry: Cambridge, U.K., 2000. Ozin, G. A. Chem. Comun.
2000, 419-432. Steed, J. W.; Atwood, J. L. Supramolecular Chemistry;
Wiley and Sons: New York, 2000. Holliday, B. J.; Mirkin, C. A. Angew.
Chem., Int. Ed. 2001, 40, 2022-2043. Brunsveld, L.; Folmer, B. J. B.;
Meijer, E. W.; Sijbesma, R. P. Chem. ReV. 2001, 101, 4071-4098.
* To whom correspondence should be addressed. E-mail: hwgibson@
vt.edu.
9
10.1021/ja012155s CCC: $22.00 © 2002 American Chemical Society
J. AM. CHEM. SOC. 2002, 124, 4653-4665
4653

A R T I C L E S
Gibson et al.
Scheme 1. Cartoon Representations of Formation of [2]-, [3]-, and
[4]-Pseudorotaxane Complexes 7, 8, and 9 from Homotritopic
Guest 1a and DB24C8 and Derivatives 2b, 3-5a
Zimmerman et al. introduced a self-assembly approach, which
guarantees structural accuracy, while eliminating steps from the
conventional multistep covalent approach.14 In this case, six
subunits were brought together by hydrogen bonding to construct
supramolecular dendritic structures up to the fourth generation.
Percec et al. achieved supramolecular dendrimers based on
building block shape and size and the interactions of the focal
point moieties.15 Recently, supramolecular chemistry has been
used to attach other functionalities to the surfaces of dendrimers
in a noncovalent manner.16
Our ultimate aim is to devise methods utilizing multitopic
guest/host systems to prepare precisely controlled multilayered
dendritic assemblies by use of orthogonal guest/host pairs.
(2) For reviews of pseudorotaxanes and rotaxanes, see: (a) Amabilino, D. B.;
Stoddart, J. F. Chem. ReV. 1995, 95, 2725-2828. (b) Gibson, H. W. In
Large Ring Molecules; Semlyen, J. A., Ed.; John Wiley and Sons: New
York, 1996; Chapter 6, pp 191-262. (c) Nepolgodiev, S. A.; Stoddart, J.
F. Chem. ReV. 1998, 98, 1959-1976. (d) Raymo, F. M.; Stoddart, J. F.
Chem. ReV. 1999, 99, 9, 1643-1664. (e) Fyfe, M. C. T.; Stoddart, J. F.
AdV. Supramol. Chem. 1999, 5, 1-53. (f) Molecular Catenanes, Rotaxanes,
and Knots; Sauvage, J.-P., Dietrich-Buchecker, C. O., Eds.; Wiley-VCH:
Weinheim, 1999. (g) Dietrich-Buchecker, C.; Rapenne, G.; Sauvage, J.-P.
Chapter 6 in ref 2f, pp 107-142. (h) Heim, C.; Udelhofen, D.; Vo¨gtle, F.
Chapter 8 in ref 2f, pp 177-222. (i) Gong, C.; Gibson, H. W. Chapter 11
in ref 2f, pp 277-321. (j) Hubin, T. J.; Busch, D. H. Coord. Chem. ReV.
2000, 200-202, 5-52. (k) Cantrill, S. J.; Pease, A. R.; Stoddart, J. F. J.
Chem. Soc., Dalton Trans. 2000, 3715-3734. (l) Mahan, E.; Gibson, H.
W. In Cyclic Polymers, 2nd ed.; Semlyen, J. A., Ed.; Kluwer Publishers:
Dordrecht, 2000; pp 415-560.
(3) Newkome, G. R.; Moorefield, C. N.; Vo¨gtle, F. Dendritic Molecules: Con-
cepts, Synthesis, PerspectiVes; VCH: Weinheim, 1996. Matthews, O. A.;
Shipway, A. N.; Stoddart, J. F. Prog. Polym. Sci. 1998, 23, 1-56. Bosman,
A. W.; Janssen, H. M.; Meijer, E. W. Chem. ReV. 1999, 99, 1665-1688.
Newkome, G. R.; He, E.; Moorefield, C. N. Chem. ReV. 1999, 99, 1689-
1746. Tully, D. C.; Fre´chet, J. M. J. Chem. Commun. 2001, 1229-1239.
Grayson, S. M.; Fre´chet, J. M. J. Chem. ReV. 2001, 101, 3819-3868.
(4) Freeman, A. W.; Koene, C.; Malenfant, P. R. L.; Thompson, M. E.; Fre´chet,
J. M. J. J. Am. Chem. Soc. 2000, 122, 12385-12386. Weener, J.-W.; Meijer,
E. W. AdV. Mater. 2000, 12, 741-746. Schenning, A. P. H. J.; Peeters, E.;
Meijer, E. W. J. Am. Chem. Soc. 2000, 122, 4489-4495. Baars, M. W. P.
L.; van Boxtel, M. C. W.; Bastiaansen, C. W. M.; Broer, D. J.; Sontjens,
S. H. M.; Meijer, E. W. AdV. Mater. 2000, 12, 715-719. Malenfant, P. R.
L.; Fre´chet, J. M. J. Macromolecules 2000, 33, 3634-3640. Newkome, G.
R.; Narayanan, V. V.; Godinez, L. A. J. Org. Chem. 2000, 65, 1643-
1649. Newkome, G. R.; He, E.; God´ınez, L. A.; Baker, G. R. J. Am. Chem.
Soc. 2000, 122, 9993-10006. Lupton, J. M.; Samuel, I. D. W.; Beavington,
R.; Burn, P. L.; Ba¨ssler, H. AdV. Mater. 2001, 13, 258-261. Maus, M.;
De, R.; Lor, M.; Weil, T.; Mitra, S.; Wiesler, U.-M.; Herrmann, A.; Hofkens,
J.; Vosch, T.; Mu¨llen, K.; De Schryver, F. C. J. Am. Chem. Soc. 2001,
123, 7668-7676. Toba, R.; Quintela, J. M.; Peinador, C.; Roman, E.; Kaifer,
A. E. Chem. Commun. 2001, 857-858.
(5) Choi, J. S.; Lee, E. J.; Choi, Y. H.; Jeong, Y. J.; Park, J. S. Bioconjugate
Chem. 1999, 10, 62-65. Choi, J. S.; Joo, D. K.; Kim, C. H.; Kim, K.;
Park, J. S. J. Am. Chem. Soc. 2000, 122, 474-480. Balogh, L.; Swanson,
D. R.; Tomalia, D. A.; Hagnauer, G. L.; McManus, A. T. Nano Lett. 2001,
1, 18-21. Kobayashi, H.; Kawamoto, S.; Saga, T.; Sato, N.; Ishimori, T.;
Konishi, J.; Ono, K.; Togashi, K.; Brechbiel, M. W. Bioconjugate Chem.
2001, 12, 587-593.
(6) Oosterom, G. E.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen P. W. N.
M. Angew. Chem., Int. Ed. 2001, 40, 1828-1849. Zhou, M.; Roovers, J.
Macromolecules 2001, 34, 244-252. Hecht, S.; Fre´chet, J. M. J. J. Am.
Chem. Soc. 2001, 123, 6959-6960. Niu, Y.; Yeung, L. K.; Crooks, R. M.
J. Am. Chem. Soc. 2001, 123, 6840-6846. Astruc, D.; Chardac, F. Chem.
ReV. 2001, 101, 2991-3024.
(7) Baars, M. W. P. L.; Kleppinger, R.; Koch, M. H. J.; Yeu, S.-L.; Meijer, E.
W. Angew. Chem., Int. Ed. 2000, 39, 1285-1288. Gorman, C. B.; Smith,
J. C. Acc. Chem. Res. 2000, 34, 60-71. Hecht, S.; Vladimirov, N.; Fre´chet,
J. M. J. J. Am. Chem. Soc. 2001, 123, 18-25. Marsitzky, D.; Vestberg,
R.; Blainey, P.; Tang, B. T.; Hawker, C. J.; Carter, K. R. J. Am. Chem.
Soc. 2001, 123, 6965-6972.
(8) Le Derf, F.; Levillain, E.; Trippe’, G.; Gorgues, A.; Salle’, M.; Sebastian,
R.-M.; Caminade, A.-M.; Majoral, J.-P. Angew. Chem., Int. Ed. 2001, 40,
224-227. Gong, L.-Z.; Hu, Q.-S.; Pu, L. J. Org. Chem. 2001, 66, 2358-
2367.
a a, R ) H, b, R ) COOCH3, c, R ) COOCH2G1, d, R ) COOCH2G2,
e, R ) COOCH2G3.
Because of the selectivity of the host imbued by the size and
shape of the cavity, pseudorotaxanes are ideally suited for the
construction of such nano-objects. In nature, this sort of process
is exemplified by viruses, which can form rodlike, filamentous,
helical, or polydedral aggregates consisting of proteins self-
assembled about a nucleic acid.17
As a beginning toward this goal, we have examined using
1H NMR spectroscopy self-assembly of a tritopic guest species,
first with a simple host, and then with dendron-functionalized
hosts to form pseudorotaxanes as described in a preliminary
account.18 In this paper, we describe equilibrium studies of these
[2]-, [3]-, and [4]-pseudorotaxane complexes, culminating in
what we believe are the first self-assembled pseudorotaxane
dendrimers.
Results and Discussion
Our strategy for self-assembling [4]pseudorotaxane dendrim-
ers is illustrated in Scheme 1. A homotritopic building block
for the core was designed to have three arms, each containing
a guest moiety (represented by the filled rectangle) capable of
binding the host moieties, represented by circles or ellipses,
located at the focal points of first, second, and third generation
dendrons. Stoddart et al. reported that dibenzo-24-crown-8
(DB24C8) and other crown ethers form pseudorotaxanes with
secondary ammonium salts.19 Association constants were esti-
mated by 1H NMR for the [2]pseudorotaxanes and a single [3]-
(13) Kawaguchi, T.; Walker, K. L.; Wilkins, C. L.; Moore, J. S. J. Am. Chem.
Soc. 1995, 117, 2159-2165.
(14) Zimmerman, S. C.; Zeng, F.; Reichert, D. E. C.; Kolotuchin, S. V. Science
1996, 271, 1095-1098. Zeng, F.; Zimmerman, S. C. Chem. ReV. 1997,
97, 1681-1712.
(15) Percec, V.; Cho, W.-D.; Ungar, G.; Yeardley, D. J. P. J. Am. Chem. Soc.
2001, 123, 1302-1315.
(16) Nagaskai, T.; Kimura, O.; Masakatsu, U.; Arimori, S.; Hamachi, I.; Shinkai,
S. J. Chem. Soc., Perkin Trans. 1 1994, 75-81. Castro, R.; Cuadrado, I.;
Alonso, B.; Casado, C. M.; Mora, M.; Kaifer, A. E. J. Am. Chem. Soc.
1997, 119, 5760-5761. Gonzalez, B.; Casado, C. M.; Alonso, B.; Cuadrado,
I.; Moran, M.; Wang, Y.; Kaifer, A. E. J. Chem. Soc., Chem. Commun.
1998, 2569-2570. Baars, M. W. P. L.; Karlsson, A. J.; Sorokin, V.; de
Waal, B. F. W.; Meijer, E. W. Angew. Chem., Int. Ed. 2000, 39, 4262-
4265. Boas, U.; Karlsson, A. J.; de Waal, B. F. M.; Meijer, E. W. J. Org.
Chem. 2001, 66, 2136-2145. Michels, J. J.; Baars, M. W. P. L.; Meijer,
E. W.; Huskens, J.; Reinhoudt, D. N. J. Chem. Soc., Perkin Trans. 2 2000,
1914-1918. Lee, J. W.; Ko, Y. H.; Park, S.-H.; Yamaguchi, K.; Kim, K.
Angew. Chem., Int. Ed. 2001, 40, 746-749. de Groot, D.; de Waal, B. F.
M.; Reek, J. N. H.; Schenning, A. P. H. J.; Kamer, P. C. J.; Meijer, E. W.;
van Leeuwen, P. W. N. M. J. Am. Chem. Soc. 2001, 123, 8453-8458.
Gibson, H. W.; Bosman, A. W.; Bryant, W. S.; Jones, J. W.; Jannsen, R.
A. J.; Meijer, E. W. Polym. Mater. Sci. Eng. 2001, 84, 66-67.
(17) Zubay, G. L. Biochemistry, 4th ed.; W. C. Brown Publishers: Boston, 1998;
pp 101-106, 734-737.
(9) Jansen, J. F. G. A.; de Brabander-van den Berg, E. M. M.; Meijer, E. W.
Science 1994, 266, 1226-1229. Jansen, J. F. G. A.; Meijer, E. W. J. Am.
Chem. Soc. 1995, 117, 4417-4418. Kovvali, A. S.; Sirkar, K. K. Ind. Eng.
Chem. Res. 2001, 40, 2502-2511.
(10) Moore, J. S. Acc. Chem. Res. 1997, 30, 402-413.
(11) Wooley, K. L.; Hawker, C. J.; Fre´chet, J. M. J. J. Am. Chem. Soc. 1991,
113, 4252-4261.
(12) Newkome, G. R.; Yao, Z.; Baker, G. R.; Gupta, V. K.; Russo, P. S.; Sanders,
M. J. J. Am. Chem. Soc. 1986, 108, 849-850. Tomalia, D. A.; Baker, H.;
Dewald, J.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith,
P. Macromolecules 1986, 19, 2466-2468.
(18) Yamaguchi, N.; Hamilton, L. M.; Gibson, H. W. Angew. Chem., Int. Ed.
1998, 37, 3275-3279.
9
4654 J. AM. CHEM. SOC. VOL. 124, NO. 17, 2002

Cooperative Self-Assembly of Dendrimers
A R T I C L E S
Scheme 2. Structures and Proton Designations of Derivatized Dibenzo-24-crown-8 Compounds
1
pseudorotaxane,19e but not for the very interesting [4]-, [5]-,
and [6]-pseudorotaxanes.19b,d,g We chose to use this molecular
recognition motif in our pursuit of dendritic pseudorotaxanes.
I. Building Blocks For Self-Assembly. 1,3,5-Tris(p-benzyl-
ammoniomethylphenyl)benzene tri(hexafluorophosphate) (1a)18,20
exhibited good solubility in acetone and acetonitrile but not in
chloroform and methylene chloride.
II. Model Complexation Studies. A. In CD3CN. The H
NMR spectra in acetonitrile-d3 were the most clearly resolved
and provide a useful basis for discussion of the complexation
processes in acetone and chloroform. As reported for 6a/
DB24C8,19 sets of signals are observed for free and complexed
DB24C8 and free and complexed ammonium salt moieties, due
1
to slow association and dissociation relative to the H NMR
time scale.
As illustrated (Scheme 3a), when DB24C8 is complexed with
the ammonium salt moiety of 1a, there are at least six and as
many as 12 nonequivalent sets of ethyleneoxy protons.21 The
signals for the uncomplexed benzylic protons, Hdu and Heu, of
guest 1a appear at 4.25 and 4.23 ppm, respectively, and move
upfield as the crown ether concentration increases (see below
for a discussion of possible reasons for this shift). The merged
signal for these protons, Hdc and Hec, in the [2]-, [3]-, and
[4]-pseudorotaxane complexes 7a, 8a, and 9a in turn (Scheme
4), is constant at 4.74 ppm.21 The percentage of ammonium
species complexed was determined by integration of these two
sets of signals; it ranged from 26.5 to 95.8% at [DB24C8]o )
10 to 50 mM. In the presence of DB24C8, the signals for Hdu
and Heu are more complicated than those of 1a alone. This can
be understood by reference to the structure of expected
[2]pseudorotaxane 7a (Scheme 4); note that the uncomplexed
NCH2 protons Hdu1 and Heu1 of the two arms exist as two
diastereotopic pairs due to the asymmetry brought about by
complex formation. However, in [3]pseudorotaxane 8a, Hdu2
and Heu2 are equivalent within each pair. Yet in 8a, Hdc and
The benzylic alcohol moieties of the first three generations
of benzyl ether dendrons11 were coupled to 2-carboxydibenzo-
24-crown-8 (2a), leading to the monotopic host dendrons 3-5
(Scheme 2).18 Model ester 2b was also prepared.18 Molecular
mechanics calculations on the targeted [4]pseudorotaxane den-
drimers 9c, 9d, and 9e (Scheme 1) yielded disk-shaped structures
with approximate “diameters” of 8, 10, and 12 nm.
(19) (a) Ashton, P. R.; Campbell, P. J.; Chrystal, E. J. T.; Glink, P. T.; Menzer,
S.; Philp, D.; Spencer, N.; Stoddart, J. F.; Tasker, P. A.; Williams, D. J.
Angew. Chem., Int. Ed. Engl. 1995, 34, 1865-1869. (b) Ashton, P. R.;
Chrystal, E. J. T.; Glink, P. T.; Menzer, S.; Schiavo, C.; Spencer, N.;
Stoddart, J. F.; Tasker, P. A.; White, A. J. P.; Williams, D. J. Chem.-Eur.
J. 1996, 2, 709-728. (c) Ashton, P. R.; Fyfe, M. C. T.; Hickingbottom, S.
K.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. J. Chem. Soc., Perkin
Trans. 2 1998, 2117-2128. (d) Fyfe, M. C. T.; Stoddart, J. F. AdV.
Supramol. Chem. 1999, 5, 1-53. (e) Chang, T.; Heiss, A. M.; Cantrill, S.
J.; Fyfe, M. C. T.; Pease, A. R.; Rowan, S. J.; Stoddart, J. F.; Williams, D.
Org. Lett. 2000, 2, 2943-2946. (f) See: Rowan, S. J.; Cantrill, S. J.;
Stoddart, J. F.; White, A. J. P.; Williams, D. J. Org. Lett. 2000, 2, 759-
762 for complexation of 6a with 2-formyldibenzo-24-crown-8 with re-
duced (but unmeasured) Ka relative to the unsubstituted crown. (g) Cantrill,
S. J.; Pease, A. R.; Stoddart, J. F. J. Chem Soc., Dalton Trans. 2000, 3715-
3734. (h) Chang, T.; Heiss, A. M.; Cantrill, S. J.; Fyfe, M. C. T.; Pease, A.
R.; Rowan, S. J.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. Org. Lett.
2000, 2, 2947-2950. (i) Amirsakis, D. G.; Garcia-Garibay, M. A.; Rowan,
S. J.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. Angew. Chem., Int.
Ed. 2001, 40, 4256-4261.
Hec of the complexed arms each consist of diastereotopic pairs,
as reflected in the additional fine structure observed in the 4.74
ppm signal.21
The aromatic protons of DB24C8 (Figure 1) can also be used
to estimate the extent of complexation. The signal (6.80 ppm)
for the complexed species (HArc) is shifted upfield, and the
splitting pattern is simpler than that (6.92 ppm) of the uncom-
(20) Ashton, P. R.; Collins, A. N.; Fyfe, M. C. T.; Glink, P. T.; Menzer, S.;
Stoddart, J. F.; Williams, D. J. Angew. Chem., Int. Ed. Engl. 1997, 36,
59-62.
(21) See Supporting Information.
9
J. AM. CHEM. SOC. VOL. 124, NO. 17, 2002 4655

A R T I C L E S
Gibson et al.
Scheme 3. (a. Left) Representation of the Complexation Site
between the Ammonium Salt Moiety of Homotritopic Guest 1a and
DB24C8, Designating the Diastereotopic Ethyleneoxy Protons
Resulting from the Fact that the Two Faces of the Crown Ether
Are Diastereotopica and (b. Right) Representation of the
Complexation Site between the Ammonium Salt Moiety of
Homotritopic guest 1a and Either Ester 2b or Crowned Dendrons
3-5, Designating the Enantiotopic Ethyleneoxy Protons Resulting
from the Fact that the Two Faces of the Crown Ether Are
Enantiotopicb
Scheme 4. Designation of the Guest Protons in the [2]Pseudo-
rotaxane Complexes 7, [3]Pseudorotaxane Complexes 8, and
[4]Pseudorotaxane Complexes 9 from Homotritopic Guest 1a and
DB24C8 and Derivatives 3-5 for NMR Signal Assignmentsa
a When R1 ) R2, as in [2]pseudorotaxane 7a or [4]pseudorotaxane 9a
(Schemes 1 and 3), there are four of each type of proton. When R1 * R2 as
in [3]pseudorotaxane 8a (Schemes 1 and 4), the fore and aft pairs are
enantiotopic if rotation of the crown ether about the ammonium ion and
other rotations about biaryl bonds are slow. bThere are in principle a
minimum of 24 types of ethyleneoxy protons. An enantiomer of the structure
shown results when the ester group occupies the position designated by
the dashed line. In [3]pseudorotaxane 8 (Scheme 4), a racemic pair (RR/
SS) and a third diastereomer (RS)SR) can form. In [4]pseudorotaxane 9
(Scheme 4), two racemic pairs (RRR/SSS) and (RRS/SSR) can form.
Additionally, in [3]pseudorotaxanes 8 (Scheme 4), if rotation of the crown
ether about the ammonium ion and other rotations about biaryl bonds are
slow, there will be two geometric isomers, one with the the dendron units
syn and one with them anti. In [4]pseudorotaxanes 9 (Scheme 4), under
conditions of slow rotation there will be two geometric isomers: up-up-
up ) down-down-down and up-up-down ) down-down-up with
respect to the relative dispositions of the dendritic substitutent on the crown
ether. All of these effects together produce complicated patterns for the
ethyleneoxy proton signals.
a
With the exception of the protons on the central 1,3,5-substituted
plexed host (HAru). On the basis of integration of these signals,
the fraction of complexed ammonium ion ranged from 26.1%
at 10 mM DB24C8 to 96.4% at 50 mM. There is good
agreement between the results from these signals and those from
the NCH2 peaks.
phenylene ring and the complexed NCH2, the numbers in the subscripts
refer to the stoichiometry of the complex, e.g., “1” for the 1:1 complex 7.
The letter following the number indicates whether the proton in question is
associated with an uncomplexed arm (“u”) or a complexed arm (“c”). (a, R
) H (from DB24C8), b, R ) COOCH3 from 2b, c, R ) COOCH2G1 from
3, d, R ) COOCH2G2 from 4, e, R ) COOCH2G3 from 5).
Turning to the aromatic protons of guest 1a, proton Hau of
the uncomplexed core 1a is detected as a singlet at 7.94 ppm.
As the concentration of DB24C8 is increased to 30 mM, a clear
triplet (J ) 1.2 Hz) emerges at 7.90 ppm due to Ha1 of [2]-
pseudorotaxane 7a (Scheme 4), while the 7.94 ppm signal
diminishes in intensity (Figure 1). As [DB24C8]o increases
further to 40 mM, the former signal grows and the latter
disappears, while a new triplet (J ) 1.6 Hz) forms at 7.52 ppm,
attributable to Ha4 of [3]pseudorotaxane 8a (Scheme 4). Further
increases in [DB24C8]o lead to the appearance and dramatic
increase in a singlet at 7.48 ppm due to Ha5 of [4]pseudorotaxane
9a (Scheme 4). Correspondingly, a doublet (J ) 1.2 Hz) at 7.73
ppm ([DB24C8]o ) 10-30 mM) is ascribed to Ha2 of 1:1
complex 7a, and the doublet (J ) 1.6 Hz) at 7.69 ppm is
attributed to Ha3 of 1:2 complex 8a (Scheme 4). The Ha1 and
1
Figure 1. The aromatic region of H NMR spectra (400 MHz, 22 °C) of
CD3CN solutions of homotritopic guest 1a (10 mM) and DB24C8 (a) 10,
(b) 20, (c) 30, (d) 40, (e) 90 mM. The first letter and the number of the
subscript designate the proton (see Schemes 3 and 4) and the second letter
whether the signal corresponds to uncomplexed (u) or complexed (c) species.
H
a2 signals are superimposed on the broad signal for complexed
NH2+ at 7.62-7.75 ppm, the latter position in agreement with
results for DB24C8/3a in CD3CN.19
The phenylene protons of 1a can be similarly analyzed as
follows, even though there is a general upfield shift of all signals
with increasing [DB24C8]o. In the uncomplexed guest 1a, Hbu
is observed as a doublet (J ) 8 Hz) at 7.58 ppm, and Hcu appears
as a doublet (J ) 8 Hz) at 7.88 ppm. Upon addition of DB24C8
(10 mM, Figure 1a), signals (doublets, J ) 8 Hz) are observed
9
4656 J. AM. CHEM. SOC. VOL. 124, NO. 17, 2002

Cooperative Self-Assembly of Dendrimers
A R T I C L E S
of 9a with minor peaks due to Hc2c and Hb2c of 8a (Scheme 4)
at [DB24C8]o ) 90 mM (Figure 2e).
The ortho, meta, and para protons Hfu and Hgu of the terminal
phenyl groups of uncomplexed 1a appear at 7.48 ppm. As
reported for DB24C8 and 6a in CD3CN,19 a new signal appears
at 7.26 ppm upon addition of DB24C8 to 1a (not shown). The
pattern does not change as [DB24C8]o increases from 10 to 90
mM; furthermore, the ratio relative to the aromatic protons (8H)
of complexed DB24C8 at 6.8 ppm is constant (0.38). We
conclude that this signal is due to the three complexed terminal
phenyl protons Hgc of species 7a, 8a, and 9a (Scheme 4) and is
part of a coupling pattern, the rest of which (Hfc) is hidden inside
the multiplet at 7.35-7.55 ppm, as also reported for DB24C8/
6a in CD3CN.19
With these assignments21 in hand, it is possible to estimate
the three association constants K1, K2, and K3 (Scheme 1) by
several corroborative methods. First, using the extent of
complexation, p, determined from the NCH2 and crown ether
signals, a Scatchard plot was constructed (Figure 2a). The
linearity of this plot indicates conclusively that the complexation
sites act independently.22 Furthermore, the slope of this plot is
proportional to the negative of the average association constant
(Kave), and the intercept is Kave (eq 1).22 Because the three guest
sites act independently, the ratios of the association constants
are known from statistics to be 3:1:1/3,22 meaning all K values
can be determined (Table 1).
Figure 2. (a. Top): Scatchard plot for complexation of homotritopic guest
1a and DB24C8 in CD3CN at 22 °C (y ) -144x + 155, r2 ) 0.967). (b.
Bottom): Scatchard plots for complexation of DB24C8 with homo-
tritopic guest 1a (O) (y ) -168x + 146, r2 ) 0.987) and deuterated
homotritopic guest 1b (0) in CD3COCD3 at 22 °C (y ) -90x + 95, r2 )
0.994). p ) fraction of ammonium sites bound. Error bars in p, (0.03
absolute; error bars in p/[DB24C8], (15% relative.
p/[DB24C8] ) -pKave + Kave
(1)
+
where p is the fraction of NH2 sites of 1a bound, and Kave is
the average microscopic association constant.
1
at 7.57 and 7.59 (minor, ∼ /3 intensity) ppm; we attribute the
Direct estimates of K1, K2, and K3 are available from the
signals for Hau, Ha1, and Ha4, which give the concentrations of
1a, [2]pseudorotaxane 7a, and [3]pseudorotaxane 8a. Unfortu-
nately, the Ha5 signal of [4]pseudorotaxane 9a, though observ-
able, is not easily integrated. However, the concentration of 9a
upfield signal at 7.57 ppm to Hb1c of [2]pseudorotaxane complex
7a and the minor signal at 7.59 ppm to Hb2c (on a complexed
arm) of [3]pseudorotaxane 8a (Scheme 4). This region is
complicated because complexes 7a, 8a, and 9a each yield
separate signals for their complexed arms. This is also the case
for the uncomplexed arms of 7a and 8a, making accurate
integration in this region impossible due to peak overlap. As
[DB24C8]o increases, the doublet at 7.59 ppm grows in intensity
at the expense of the 7.57 ppm signal, and at the same time a
new doublet (J ) 8 Hz) emerges at 7.56 and grows as
[DB24C8]o increases. The final 7.56 ppm signal is attributed
to Hb3c of [4]pseudorotaxane complex 9a (Scheme 4, Figure
1e). The minor doublet (partially hidden) at 7.55 ppm for
[DB24C8]o ) 90 mM is attributed to Hb2u (uncomplexed arm)
of residual [3]pseudorotaxane complex 8a (Scheme 4, Fig-
ure 1e); both the NCH2 and DB24C8 aromatic signals indi-
can be determined by realizing that N1a + N7a + N8a + N9a
)
1, where N represents the mole fraction of each species. The
total integral from 7.1 to 8.0 ppm represents a total of 30
+
aromatic protons plus the protons of the complexed NH2
moieties of the core structure 1a. Therefore, N1a ) #Hau/3, N7a
) #Ha1, and N8a ) #Ha4/2; N9a was estimated by difference.
Furthermore, the percent complexation was independently
checked for the crown ether versus the NCH2 moieties. These
K values (Table 1) are in reasonable agreement with the values
derived from the Scatchard treatment, but somewhat higher.
Generally, we have observed that K decreases with [DB24C8]o
in these systems; possible reasons for this are discussed below.
Because the Scatchard plot includes all the concentrations, it
yields a lower average K than direct determinations at lower
concentrations. Kave (1.5 × 102 M-1) is lower than the value of
420 M-1 reported for complexation of dibenzylammonium
hexafluorophosphate (6a) and DB24C8 in CD3CN.19 Because
if all else were equal the average K value for 1a would be the
same as the K value for 6a/DB24C8, it seems that binding of
the crown ether to the guest units of homotritopic 1a is less
favored than its binding to 6a. We attribute this partially to an
+
cate that >95% of the NH2 units are complexed at this
concentration.
In the case of the Hcu signal (7.88 ppm) of homotritopic guest
1a, the changes are analogous, producing doublets, all with J
) 8 Hz, with chemical shifts of ∼7.84, ∼7.86, and ∼7.88 ppm
(Figure 1, all move upfield with increasing [DB24C8]o). As
[DB24C8]o increases from 10 to 90 mM, the 7.88 ppm peak
disappears, leaving two overlapping doublets (J ) 8 Hz) at 7.84
(major) and 7.86 (minor) ppm. These signals are assigned as
follows: 7.84 ppm, Hc3c of [4]pseudorotaxane 9a; 7.86 ppm,
Hc2c of [3]pseudorotaxane 8a; 7.88 ppm, Hc1c of [2]pseudoro-
taxane 7a (Scheme 4). Note the symmetry of the residual signals
at 7.78 and 7.56 ppm, respectively, representing Hc3c and Hb3c
(22) Freifelder, D. M. Physical Biochemistry; W. H. Freeman and Co.: New
York, 1982; pp 659-660. Marshall, A. G. Biophysical Chemistry; Wiley
and Sons: New York, 1978; pp 70-77. Connors, K. A. Binding Constants;
Wiley and Sons: New York, 1987; pp 78-86.
9
J. AM. CHEM. SOC. VOL. 124, NO. 17, 2002 4657

A R T I C L E S
Gibson et al.
Table 1. Association Constants for Model Psuedorotaxane Complexes, 22 °C
host/guest system
solvent
10-2 × K (M-1
)
10-2 × K (M-1
)
10-2 × K (M-1
)
10-6 × K a (M-3
)
1
2
3
o
DB24C8/1a
CD3CN
4.4 ((0.1)b
3.1 ((0.4)d
3.7 ((1.7)e
3.3 ((0.5)f
7.3 ((1.3)g
1.9 ((0.3)h
3.2 ((0.2)i
2.0 ((0.1)j
1.8 ((0.1)k
1.4 ((0.2)b
1.0 ((0.2)d
1.3 ((0.2)e
1.1 ((0.2)f
2.2 ((0.9)g
0.64 ((0.10)h
0.41 ((0.04)b
0.35 ((0.04)d
0.57 ((0.13)e
0.37 ((0.05)f
0.48 ((0.14)g
0.21 ((0.04)h
2.5 ((0.7)c
1.1 ((0.6)c
2.7 ((2.4)c
1.3 ((0.6)c
7.7 ((7.0)c
1.7 ((0.7)c
DB24C8/1a
CD3COCD3
DB24C8/1b
DB24C8/6a
2b/6a
DB24C8/6b
DB24C8/1a
CD3COCD3
CD3COCD3
CD3COCD3
CD3COCD3
CDCl3
3.9 ((0.4)l
a Overall association constant for formation of [4]pseudorotaxane 9a from 1 mol of 1a or 1b and 3 mol of DB24C8; Ko ) K1K2K3. b Relative concentrations
were estimated by integration of Ha signals for free 1a (7.94 ppm, Hau, 3H), [2]- (7a, 7.90 ppm, Ha1, 1H), and [3]-pseudorotaxanes (8a, 7.52 ppm, Ha4, 1H);
[4]-pseudorotaxane (9a) concentration was determined by difference using values of extent of complexation estimated from both complexed and “uncomplexed”
NCH2 and crown ether aromatic protons, which also yielded the concentration of the “uncomplexed” crown ether. Range of initial concentrations of 1a/
DB24C8 used: for K1, 10/10 to 10/60 mM; for K2, 10/20 to 10/60 mM/mM; for K3, 10/30 to 10/60 mM. Error bars are standard deviations from multiple
independent integrations of the spectra. c Error cited is average deviation from the nominal value calculated using both the maximum and the minimum
values for K1, K2, and K3 based on the individual error bars. d By Scatchard plot analysis (Figure 2a) using values of extent of complexation estimated from
both complexed and “uncomplexed” NCH2 and crown ether aromatic protons, which also yielded the concentration of the “uncomplexed” crown ether, over
the range of initial concentrations of 1a/DB24C8 from 10/10 to 10/90 mM/mM. Kave ) (-slope + intercept)/2 ) 1.5 × 102 M-1 ) 4.33K3; K2 ) 3K3 and
K1 ) 9K3. Error bars are based on maximum and minimum slope fits. e The molar ratios of 1a, 7a, 8a, and 9a were determined by integration of Hau (7.96
ppm, 3H, 1a), Ha1 (7.94 ppm, 1H, 7a), Ha2 (7.82 ppm, 2H, 7a), Ha3 (7.80 ppm, 2H, 8a), and Ha5 (7.67 ppm, 3H, 9a) (Scheme 4). The signals were integrated
by the cut and weigh method, taking into account the facts that Ha2 and Ha3 ride atop the signal for complexed NH2+ and that Ha4 overlaps Ha5. In the former
case, the baseline was corrected, and in the latter, since both Ha3 and Ha4 are derived from 8a, by subtraction of one-half the integral of Ha3. The concentration
of uncomplexed DB24C8 was determined by integration of the well resolved Hbc (3.91 ppm) versus Hbu (3.83 ppm) (Scheme 2). The results from the
following initial concentrations of 1a/DB24C8 were used to evaluate K1, 10/20, 10/20, 10/30 mM/mM; K2, 10/30, 10/40, 10/50, 10/60 mM/mM; K3, 10/20,
10/30, 10/40, 10/50, 10/60 mM/mM. Error bars are the standard deviations. f By Scatchard plot analysis (Figure 2b) using values of extent of complexation
estimated from both complexed and “uncomplexed” NCH2 and â-OCH2 signals, which also yielded the concentration of the “uncomplexed” crown ether,
over the range of initial concentrations of 1a/DB24C8 from 10/10 to 10/90 mM/mM. Kave ) (-slope + intercept)/2 ) 1.6 × 102 M-1 ) 4.33K3; K2 ) 3K3
and K1 ) 9K3. Error bars are based on maximum and minimum slope fits. g By deconvolution of “uncomplexed” NCH2 signals to determine the relative
concentrations of 1a, [2]- (7a), and [3]-pseudorotaxanes (8a); the extent of complexation was estimated from both complexed and “uncomplexed” NCH2 and
â-OCH2 signals, which also yielded the concentration of the “uncomplexed” crown ether. The concentration of the [4]pseudorotaxane (9a) was determined
by difference. The results from solutions of the following initial concentration ranges of 1a/DB24C8 were used: for K1, from 10/10 to 10/60 mM/mM; for
K2, from 10/10 to 10/60 mM/mM; for K3, from 10/30 to 10/60 mM/mM. Error bars are standard deviations. h By Scatchard plot analysis (Figure 2b) using
values of extent of complexation estimated from both complexed and “uncomplexed” NCH2 and â-OCH2 signals, which also yielded the concentration of
the “uncomplexed” crown ether, over the range of initial concentrations of 1b/DB24C8 from 10/10 to 10/90 mM/mM. Kave ) (-slope + intercept)/2 ) 93
M-1 ) 4.33K3; K2 ) 3K3 and K1 ) 9K3. Error bars based on maximum and minimum slope fits. i By integration of complexed versus “uncomplexed” NCH2
and γ-OCH2 signals at initial concentrations of 6a/DB24C8 ) 20/20 mM/mM. j By integration of Hdc versus Hdu signals at initial concentrations of 2b/6a
) 20.4/20.3 mM/mM. k By integration of complexed versus “uncomplexed” NCH2 signals over a range of initial concentrations of 6b/DB24C8 from 10/10
to 10/60 mM/mM. l By integration of Hc2u and Hb2u of [3]pseudorotaxane 8a versus Hc3c and Hb3c of [4]pseudorotaxane 9a (Scheme 4), respectively, in a
solution initially 30 mM in DB24C8 containing solid 1a in an amount equivalent to 10 mM had it all dissolved; 90.0 ( 0.5% of the solid dissolved.
unaccounted equilibrium process that competes more strongly
with pseudorotaxane formation in the case of 1a (see below).
Heu beginning at 4.64 and 4.58 ppm in 1a shift upfield and
disintegrate into broader multiplets with increasing concentration
of DB24C8 and eventually disappear with 9 equiv of DB24C8.
The behavior of the signals for Hdu and Heu is partially
attributable to the existence of the [2]- and [3]-pseudorotaxane
complexes 7a and 8a. As illustrated in Scheme 4, when one of
the arms is occupied with DB24C8, the initially equivalent pairs
of Heu and Hdu protons of 1a each become nonequivalent
(diastereotopic) in 7a, meaning that there are two pairs of
nonequivalent benzylic protons, Hd1u, Hd1′u, He1u, and He1′u, on
each uncomplexed arm. When two of the arms are complexed
with DB24C8 in 8a, the two Hdu protons and two Heu protons
of 8a are once again equivalent by symmetry as shown.
The gradual upfield shifts observed for Hdu and Heu signals
were initially hypothesized to be the result of the increased
B. In CD3COCD3. 1. Tritopic Guest 1a with DB24C8. The
1
aliphatic region of the H NMR spectra of solutions of the
homotritopic molecule 1a and DB24C8 in acetone-d6 (Figure
3) again reveals slow association and dissociation. The signal
assignments were made with the aid of the COSY spectrum.21
In CD3CN the ethyleneoxy proton signals were not readily
integrated individually, whereas in CD3COCD3 the signals for
the complexed and uncomplexed â-protons, in particular, are
observed with baseline separation, allowing facile quantitation
of the fraction of crown ether involved in complexation.
1
Peaks in the aromatic region of the H NMR spectra of
solutions of 1a and DB24C8 were assigned by COSY (Figure
4) and analogy to CD3CN spectra: Hau of 1a at 7.98 ppm, Ha1
of [2]pseudorotaxane 7a at 7.94 ppm, Ha2 of 7a at 7.73 ppm,
Ha3 of [3]pseudorotaxane 8a at 7.69 ppm, and Ha5 of [4]-
pseudorotaxane 9a at 7.66 ppm (Scheme 4). The Hgc signal for
pseudorotaxanes 7a, 8a, and 9a (Scheme 4) at 7.3 ppm is well
resolved; comparing its integral with that for the total aromatic
proton resonances of the crown ether (6.8-7.0 ppm) allows an
independent assessment that agrees well with results from the
â-OCH2 and NCH2 signals.
-
concentration of “free” PF6 with respect to the concentration
of uncomplexed ammonium salt moieties, that is, ion pairing
-
of the “free” PF6 with the uncomplexed ammonium species.
The pseudorotaxane geometry does not allow tight ion pairing,
-
so the “free” PF6 ions resulting from complexation are
potentially available to interact with uncomplexed ammonium
ion moieties, as we had previously observed in a paraquat-based
pseudorotaxane system.23 However, addition of n-Bu4NPF6 in
concentrations up to 2 M to 10 mM solutions of 1a (without
An intriguing observation in the 1H NMR spectra of solutions
of 1a and DB24C8 is the behavior of the signals for Hdu and
Heu (Figure 3). Two sharp singlets corresponding to Hdu and
(23) Yamaguchi, N.; Nagvekar, D. S.; Gibson, H. W. Angew. Chem., Int. Ed.
1998, 37, 2361-2364.
9
4658 J. AM. CHEM. SOC. VOL. 124, NO. 17, 2002

Cooperative Self-Assembly of Dendrimers
A R T I C L E S
chemical shifts of Hdu and Heu. These results indicate that ion
pairing is not the source of the observed shifts.
2. Monotopic Deuterated Guest 6b and DB24C8. To gain
further insight into these signal pattern changes for Hdu and Heu,
deuterated dibenzylammonium hexafluorophosphate 6b was
prepared,21 and its complexation was examined. As [DB24C8]o
was increased from 0 to 140 mM in a solution 10 mM in 6b,
the signal for the uncomplexed NCH2 moved upfield 0.05 ppm
as compared to 0.3 ppm for 1a in Figure 3. The 31P resonance
did not change, and 19F chemical shift changes were relatively
small (<0.5 ppm). These results argue against ion pairing of
the PF6 anions “freed” by the complexation with the accessible
uncomplexed sites.
1
3. Tritopic Deuterated Guest 1b and DB24C8. The H
NMR spectrum of deuterated homotritopic molecule 1b21 in
acetone-d6 revealed the signal for the Hd proton at 4.58 ppm,
the same position as in 1a. In spectra of solutions of guest
1b and DB24C8,21 the signal for Hdu did not shift upfield as
dramatically or change its shape with increased concentra-
tion of DB24C8 as we observed with protiated analogue 1a
(Figure 3)!
To explain why the NCH2 signals in completely uncomplexed
1a are shifted and why discrete signals for 1a, 7a, and 8a are
not observed at specific fixed chemical shifts, we propose
+
nonpseudorotaxane complexation of the unthreaded NCH2
moieties, that is, of the exo type, either “perching” or “nesting”,25
which is well known.26 Thus, as the crown ether concentration
is increased, the fraction of ammonium ion moieties that are
involved in this latter type of complexation also increases.
Because this equilibration is rapid on the NMR time scale, the
signals are time-averaged. The increased electron density on
1
Figure 3. The aliphatic region of H NMR spectra (400 MHz, 22 °C) of
CD3COCD3 solutions of homotritopic guest 1a (10 mM) and DB24C8 (a)
0, (b) 10, (c) 20, (d) 30, (e) 40, (f) 50, (g) 60, and (h) 90 mM. The first
letter and number of the subscript designate the proton (see Schemes 3 and
4) and the second letter whether the signal corresponds to uncomplexed
(u) or complexed (c) species.
+
the NH2 moieties as a result of this H-bonding and also the
shielding effect of the benzo groups of the proximal crown ether
cause an upfield shift of the NCH2 protons. In the deuterated
homotritopic 1b there are only Hd protons; the deuterons on
the “external” benzylic positions are less acidic than the Hd
protons,27 and this apparently prohibits, or at least inhibits,
formation of the exo complexes and/or alters the co-conforma-
tions of the pseudorotaxane moieties in such a way that no
chemical shift change results from increased [DB24C8].
4. Homotritopic Guest 1a and Dibenzo-18-crown-6. For
evidence in support of exo complexation, homotritopic guest
1a (10 mM) was examined in acetone-d6 in the presence of 30
mM dibenzo-18-crown-6 (DB18C6), which is too small to form
a pseudorotaxane. Indeed, in accordance with the hypothesis
of formation of exo hydrogen bonded complexes, the NCH2
protons shifted upfield by 0.05 ppm. However, with deuterated
dibenzylammonium hexafluorophosphate 6b there were no
signficant changes in the chemical shifts of the NCH2 protons.
Protiated analogue 6a (20 mM) in the presence of DB18C6
(saturated, <10 mM) also revealed a small upfield shift; the
(24) Below -40 °C all of the crown ether was consumed based on the â-proton
signals. Because of the lack of resolution of appropriate signals for 1, 7a,
8a, and 9a, it was not possible to estimate K1, K2, and K3.
(25) Newcomb, M.; Moore, S. S.; Cram, D. J. J. Am. Chem. Soc. 1977, 99,
6405-6410.
(26) Metcalfe, J. C.; Stoddart, J. F.; Jones, G. J. Am. Chem. Soc. 1977, 99,
8317-8319. Izatt, R. M.; Lamb, J. D.; Izatt, N. E.; Rossiter, B. E., Jr.;
Christensen, J. J.; Haymore, B. L. J. Am. Chem. Soc. 1979, 101, 6273-
6276. Doxsee, K. M.; Francis, P. E., Jr.; Weakley, T. J. R. Tetrahedron
2000, 56, 6683-6691 and references therein.
(27) For a comparison of the acidity of H2O versus D2O (pKa ) 15.4 and 17.2,
respectively, at 25 °C in H2O) see: Isaacs, N. Physical Organic Chemistry,
2nd ed.; Longman Scientific and Technical: Essex, U.K., 1995; p 244.
Figure 4. Aromatic region of COSY spectrum of a CD3COCD3 solution
of homotritopic guest 1a (10 mM) and DB24C8 (30 mM). The first letter
and number of the subscript designate the proton (see Scheme 4) and the
second letter whether the signal corresponds to uncomplexed (u) or
complexed (c) species.
DB24C8) had no effect on the chemical shifts for Hdu and Heu.
Furthermore, low-temperature NMR spectroscopy on a solution
of 1a/DB24C8 (10/30 mM)24 did not reveal any change in the
9
J. AM. CHEM. SOC. VOL. 124, NO. 17, 2002 4659

A R T I C L E S
Gibson et al.
lower saturation concentration of DB18C6 in a solution of
ammonium salt 6a relative to that in triammonium salt 1a (∼40
mM) is consistent with stronger exo complexation of 1a,
possibly due to its higher charge density and opportunities for
multisite H-bonding and other attractive interactions, for
example, π-stacking. It should be noted that the extent of exo
complexation with DB18C6 is expected to be lower than with
DB24C8 since the latter possesses twice as many nonphenolic
ether oxygen atoms which are more basic than the phenolic ether
oxygen atoms.
by integration of the crown ether aromatic signals (6.8-7.0 ppm)
and that of Hgc of pseudorotaxanes 7a, 8a, and 9a (Scheme 4)
at 7.3 ppm. The K’s (Table 1) are close to the relative, statistical
values (3:1:1/3) anticipated for independent guest sites in the
homotritopic species,22 but somewhat higher, particularly for
K1, than those resulting from the Scatchard plot. The reason
for this lies in the concentration dependence of the K values;
the Scatchard plot gives an average value over the entire
concentration range of DB24C8, while the integration technique
was used only at lower [DB24C8]o.
A significant aspect of the formation of exo complexes is
that the “free” ammonium ion and crown ether moieties are
consumed, thereby reducing the true concentrations of both
species. Therefore, the calculated association constants are
underestimated. The formation of exo hydrogen bonded com-
plexes nicely rationalizes both the shifts of “uncomplexed”, that
is, nonpseudorotaxane type, benzylic NCH2 protons (and other
signals), and the decrease in calculated K values with increasing
concentration of host moieties.
The Ka for [2]pseudorotaxane formation from DB24C8 with
deuterated 6b is ca. one-half that with protiated 6a (Table 1).
Variable temperature (+22 to -60 °C) H NMR spectroscopy
1
on a solution of DB24C8/6a produced results similar to those
reported for this system in CD3CN, showing some curvature in
a van’t Hoff plot.19b Although this has been attributed to “a
nonneglible heat capacity(∆C°p)”,19b we suggest that it is due
to the fact that the association constants for pseudorotaxane
formation are underestimated to differing extents at different
temperatures due to the fact that the exo complexation and
pseudorotaxane complexation do not have the same temperature
dependence; recall that the concentrations of the uncomplexed
host and guest species (here DB24C8 and 6a) have been
assumed to include all species not in the pseudorotaxane state,
thereby failing to take into account exo complexation. The K
values are thereby underestimated.
5. Association Constants of Homotritopic Guests 1a and
1b with DB24C8. The association constants for the pseudoro-
taxane complexes of 1a and DB24C8 in acetone-d6 were first
estimated via the Scatchard treatment (Figure 2b, Table 1) based
on integration of the complexed and “uncomplexed” NCH2 and
crown ether signals. Because the plot is linear, binding is
noncooperative, that is, statistical. Similarly, the association
constants for the pseudorotaxane complexes of deuterated
homotritopic guest 1b and DB24C8 in acetone-d6 were estimated
via the Scatchard treatment (Figure 2b, Table 1). The lower
association constants for 1b as compared to those of 1a are
presumably due to the lower acidity27 of the benzylic deuterons
of the ammonium salt moieties in 1b relative to the protons of
1a, since CH- -O bonding is known to be important in these
6. 2-Carbomethoxydibenzo-24-crown-8 (2b) with Diben-
zylammonium Hexafluorophosphate (6a). 2-Carbomethoxy-
dibenzo-24-crown-8 (2b) serves as a good model for dendrons
3-5. Upon complexation with 6a,21 the Hdc and Hdu signals
are well resolved, providing one means of assessing the extent
of complexation. The integrals for the well-resolved complexed
versus uncomplexed γ-protons (Schemes 2 and 3b) provide a
second independent estimate of the extent of complexation. The
signal for the complexed γ-protons reveals more than one type
of environment (Scheme 3b). The association constant for [2]-
pseudorotaxane formation from ester 2b and 6a was lower than
that for DB24C8 with 6a (Table 1), as expected because of the
electron-withdrawing effect of the ester moiety.19f
systems.19 Note that again the average K value (1.6 × 102 M-1
)
for 1a/DB24C8 is less than the value for monotopic guest 6a
with DB24C8 (Table 1); we attribute this partially to the greater
propensity of tritopic 1a to participate in exo complexation
relative to the simpler guest 6a. This could be due to
+
simultaneous bonding to more than one NH2 site and/or the
increased possibilities for attractive interactions of the aromatic
rings of the host and guest 1a, coupled with screening of the
three proximate ionic charges.
C. In CDCl3. 1. Tritopic Guest 1a with DB24C8. Figure 5
shows the 1H NMR spectrum of a CDCl3 solution of DB24C8
(30 mM) and homotritopic core molecule 1a (as a solid in an
amount that corresponded to 10 mM had it completely dis-
solved). Note that 1a is not soluble in CDCl3. Again the
exchange process is slow.
A second analysis was based on direct integration of the
signals for Hau of 1a, Ha2 of 7a, Ha3 of 8a, and Ha5 of 9a. The
K values agree well with those derived from the Scatchard plot
(Table 1), but as noted above are slightly higher.
In contrast to spectra in acetone-d6, there is only one set of
NCH2 signals. We initially concluded,18 therefore, that all of
the homotritopic ammonium salt 1a in solution was completely
complexed; that is, only [4]pseudorotaxane 9a and DB24C8
were present. However, careful integration indicated that <100%
of the ammonium ion moieties of 1a were complexed in these
solutions. This conclusion was reached on the basis of two
analyses. In the first analysis, the region from 4 to 4.3 ppm
revealed an excess of protons over the expected eight from
R-OCH2 moieties when compared to the aromatic proton signals
of the crown ether (6.76-6.95 ppm). From this “excess”
integral, attributed to uncomplexed NCH2, and that for the
complexed NCH2 signal at 4.6-4.7 ppm, we found that 89.5%
of the NH2+ units were complexed and 10.5% uncomplexed at
[DB24C8]o ) 30 mM. By analogy to the CD3CN spectra, the
A third analysis involved the “uncomplexed” (actually time-
averaged uncomplexed and exo complexed) benzylic protons
of homotritopic guest 1a, that is, Hdu and Heu (Figure 3). We
assigned the three pairs of signals for these protons in 1a, [2]-
pseudorotaxane 7a, and [3]pseudorotaxane 8a. The three species
revealed different peak separations for Hdu and Heu, but the pairs
were easily identified because the intensities of the two peaks
in each pair were by definition identical. The signals were
deconvoluted to provide three distinct pairs of peaks which were
integrated to estimate the relative amounts of 1a, 7a, and 8a.
The relative amount of [4]pseudorotaxane 9a could then be
estimated as outlined above by difference, based on the
percentage of 1a that had been complexed as deduced from the
relative integrals for Hdc + Hec versus Hdu + Heu and confirmed
9
4660 J. AM. CHEM. SOC. VOL. 124, NO. 17, 2002

Cooperative Self-Assembly of Dendrimers
A R T I C L E S
1
Figure 6. The aliphatic region of H NMR spectra (400 MHz, 22 °C) of
(a) a 10 mM CDCl3 solution of third generation dendron 5 and (b) a 10
mM CDCl3 solution of third generation dendron 5 mixed with 1 mol equiv
of solid monotopic guest 6a. The first letter and number of the subscript
designate the proton (see Schemes 2 and 4) and the second letter whether
the signal corresponds to uncomplexed (u) or complexed (c) species.
1
Figure 5. The H NMR spectrum (400 MHz, 22 °C) of a 30 mM CDCl3
1
solution of DB24C8 mixed with
/ mol equiv of solid tritopic guest 1a
3
Table 2. Supramolecular Formulas, Calculated Supramolecular
Weights, and Observed (Ms) Mass/Charge Ratios
after 18 h. The first letter and number of the subscript designate the proton
(see Schemes 3 and 4) and the second letter whether the signal corresponds
to uncomplexed (u) or complexed (c) species.
structure
molecular formula
calcd MW
obs m/z
9a-PF6
8a-2PF6
[C48H48N3P2F12(C24H32O8)3]+
[C48H48N3PF6(C24H32O8)2]+
[C48H47N3PF6(C24H32O8)]+
2300.9
1707.8
1258.6
1112.6
2300.5a1,b
1707.8a2
1258.6a3
1112.6 a4
small doublets at 7.62 and 7.53 ppm were assigned to Hc2u and
Hb2u of [3]pseudorotaxane 8a, respectively, and the major
doublets at 7.67 and 7.47 ppm to Hc3c and Hb3c of [4]-
pseudorotaxane 9a (Scheme 4), respectively. In the second
analysis, integration of the well-resolved signals at 7.53 and
7.47, using the crown ether aromatic proton signal integral as
a reference, indicated at [DB24C8]o ) 30 mM that 9.4% of the
dissolved 1a was present as [3]pseudorotaxane 8a and 90.6%
as [4]pseudorotaxane 9a. The results from the two analyses are
in excellent agreement, allowing K3 to be determined (Table
1). Thus, a small percentage of [2]pseudorotaxane 7a must exist
in these CDCl3 solutions, although it was not detected.
7a-PF6-HPF6
7a-PF6-2HPF6 [C48H46N3(C24H32O8)]+
a FAB mass spectrum recorded in the positive ion mode using 3-ni-
trobenzyl alcohol (3-NBA) as the matrix; sample prepared by slow
evaporation (25 °C) of an acetone solution 10 mM in 1a and 30 mM in
DB24C8. (1) 4%, (2) 33%, (3) 5%, (4) 11% of base peak at m/z ) 471.2
(DB24C8 + Na)+. b High-resolution FAB: 2300.9452 (M)+, 2301.9493
(M + 1)+, 2303.9608 (M + 2)+ in relative intensities 71:100:73; calcd
2300.9423 (M)+, 2301.9457 (M + 1)+, 2303.9614 (M + 2)+ in relative
intensities 75:100:69.
those of uncomplexed 5, nor were there changes in the aromatic
proton signals of the third generation dendron. However, shifts
of the signals for benzylic ether protons Hk and the ethyleneoxy
protons were observed, but no uncomplexed NCH2 (Hdu) signal
could be detected. The total concentration of 6a was 5.59 mM
based on the integral of the 4.55 ppm signal for Hdc + Hec (4H
per 6a) versus that of all of the benzylic proton signals Hk, Hn,
Hq, and Ht (30H per 5). All of 6a was present in solution as the
[2]pseudorotaxane complex.
While it is not possible to determine the first two association
constants in this solvent, the amount of homotritopic guest 1a
that dissolved was determined from the integrals noted above;
91 ( 1% of the solid 1a dissolved in 30 mM DB24C8, pro-
ducing a 9.1 ( 0.1 mM total concentration of 1a-based species,
that is, [3]pseudorotaxane 8a, and [4]pseudorotaxane 9a.
2. 2-Carbomethoxydibenzo-24-crown-8 (2b) with Homo-
tritopic Guest 1a. Complexation was evidenced by the 1H NMR
spectrum21 of a 15 mM CDCl3 solution of 4-carbomethoxy-
dibenzo-24-crown-8 (2b) with solid 1a in an amount which if
dissolved corresponded to 5.0 mM. After 22 h, 73.1% of the
D. Mass Spectrometry. The FAB MS spectrum exhibited
signals corresponding to the [4]pseudorotaxane complex 9a after
the loss of a PF6 counterion, the [3]pseudorotaxane complex
8a with only one PF6 counterion, and the [2]pseudorotaxane
complex 7a, both intact and after loss of PF6 .
- 21 The presence
-
-
+
solid 1a had dissolved ([1a]total ) 3.65 mM), and the NH2
moieties were 83% complexed as determined from the integrals
of the Hdc + Hec signals at 4.6-4.8 versus the Hdu + Heu peaks
at 4.25-4.35 ppm and the integral of all of the OCH2 signals
of the crown ether.
of [4]pseudorotaxane 9a was confirmed by high-resolution FAB
MS (Table 2).
III. Dendrimer Self-Assembly: Tritopic Guest 1a with
First, Second, and Third Generation Dendrons 3-5. A. In
CD3COCD3. H NMR spectra of solutions of 1a with first
3. Third Generation Dendron 5 with Dibenzylammonium
Hexafluorophosphate (6a). 1H NMR spectra of a 10 mM
solution of third generation dendron 5 in chloroform-d mixed
with 1 mol equiv of solid dibenzylammonium hexafluorophos-
phate (6a) were recorded periodically; no changes were noted
over a 24 h period (Figure 6). The signals for the benzylic
protons Hn, Hq, and Ht of dendron 5 (Scheme 2) in the
[2]pseudorotaxane complex 5:6a were not distinguishable from
1
(Figure 7), second,21 and third (Figure 8) generation dendrons
3, 4, and 5 individually in acetone-d6 exhibit signals for com-
plexed and free moieties due to slow association and dissocia-
tion. The signals for Hdu and Heu of 1a (singlets at 4.64 and
4.58 ppm) gradually shifted upfield and changed their shapes
to give multiple peaks, while their intensity decreased as the
9
J. AM. CHEM. SOC. VOL. 124, NO. 17, 2002 4661

A R T I C L E S
Gibson et al.
7 and 8),21 which may be explained in terms of the interaction
of neighboring complexed dendron units. Because of the
additional aromatic protons present in dendrons 3, 4, and 5,
most of the aromatic proton signals of the homotritopic core
1a are not readily analyzed, although importantly Hau at 7.96
ppm was clearly resolved and integratable in all cases, as with
the model system 1a/DB24C8.
The second and third generation dendritic systems were quan-
titatively analyzed via the “uncomplexed” (i.e., time averaged
exo hydrogen bonded complexed25,26 and truly uncomplexed)
NCH2 signals assigned as discussed above for the model sys-
tem: the downfield pair to 1a, the next upfield pair to the [2]-
pseudorotaxane 7, and the most upfield pair to the [3]pseudo-
rotaxane 8 (Scheme 4), keeping in mind that the two peak inten-
sities in a pair were equal. Distinct signals could be observed
and integrated up to 30 mM dendron (above a certain concentra-
tion only the downfield signal of the [3]pseudorotaxane 8 was
clearly resolved, and its integral was doubled for the estimation).
The diminishing signals all gradually merged with the R-eth-
yleneoxy multiplet at high dendron concentrations. Integration
of the 7.96 ppm peak for Hau of 1a provided corroboration of
the concentration of this species. This method could not be used
with the first generation system because Hdu + Heu overlaps
with complexed R-ethyleneoxy signals (see Figure 7e-g).
1
Figure 7. The aliphatic region of H NMR spectra (400 MHz, 22 °C) of
CD3COCD3 solutions of homotritopic guest 1a and first generation
monotopic dendron 3 at (a) 0/10, (b) 10/0, (c) 10/10, (d) 10/30, (e) 10/40,
(f) 10/50, and (g) 10/60 mM initial concentrations. The first letter of the
subscript designates the proton (see Schemes 2 and 4) and the second letter
whether the signal corresponds to uncomplexed (u) or complexed (c) species.
For the first generation system based on 3, determination of
the concentrations of uncomplexed 1a and pseudorotaxanes 7c
and 8c was achieved via the signals for Hau (7.96 ppm), Ha2
(7.76 ppm), and Ha3 (7.73 ppm); the concentrations of 9c were
determined by difference.
Because the concentrations of 1a, [2]pseudorotaxanes 7, [3]-
pseudorotaxanes 8, and [4]pseudorotaxanes 9 were known, the
association constants were known (Table 3). It is especially
noteworthy that the ratios of K1:K2:K3 exceed the statistical ratio
expected for independent (noncooperative) binding by the three
NH2 sites of 1a, that is, 3:1:1/3,22 demonstrating that positiVe
+
cooperatiVity driVes the complexation processes!
To verify this remarkable result, we constructed Scatchard
plots, which are independent of the calculations of the individual
association constants (Figure 9). The plots for all three genera-
tion dendron systems are clearly nonlinear and possess maxima
as expected for positively cooperative binding.22 By comparison
of the overall association constant (Ko) values (Table 3), it is
apparent that the extent of cooperativity increases as the size
of the dendron increases. We attribute this phenomenon to the
dendrons’ ability to screen the ionic core (1a) from the nonpolar
bulk solvent in a micelle-like structure: the larger the dendron,
the larger the effect. Evidence in support of the encapsulation
of the triammonium ion in the systems derived from the
1
Figure 8. The aliphatic region of H NMR spectra (400 MHz, 22 °C) of
CD3COCD3 solutions of homotritopic guest 1a and third generation
monotopic dendron 5 at (a) 0/10, (b) 10/0, (c) 10/10, (d) 10/20, (e) 10/30,
(f) 10/40, (g) 10/50, and (h) 10/60 mM initial concentrations. The first letter
and number of the subscript designate the proton (see Schemes 2 and 4)
and the second letter whether the signal corresponds to uncomplexed (u)
or complexed (c) species.
+
dendrons is afforded by the complexed NH2 signals. In the
case of the DB24C8 system in acetone-d6, the signal is observed
as a broad peak at 7.85 ppm (Figure 4) and with first generation
system 3 at 7.74 ppm, while in second and third generation
systems derived from 4 and 5 it appears as a sharp peak at 8.01
ppm (not shown). This is taken to mean that in the pseudoro-
taxanes derived from the latter two hosts, exchange of these
protons is slow because they are effectively “sealed” in the
interior of the assembly. π-Stacking28a and T-type N+C-H- -π
interactions28b may also play a role.
concentration of crown-functionalized dendron 3, 4, or 5 was
increased, as observed with the model system 1a/DB24C8
(Figure 3).
The ethyleneoxy protons of the dendrons are complicated
because of the substituted crown ether’s intrinsic dissymmetry
(Scheme 2). The ethyleneoxy protons of the complexed crown
ether moieties of the dendrons are even more complicated due
to the enantiotopism (and possibly geometic isomerism) (Scheme
3b) and afford no quantitative information. The signals for the
benzylic protons of the dendrons (Scheme 2) undergo distin-
guishable upfield chemical shifts upon complexation (Figures
As shown in Table 1, for noncooperative binding of DB24C8
by 1a, the Ko value is lower than with second and third
9
4662 J. AM. CHEM. SOC. VOL. 124, NO. 17, 2002

Cooperative Self-Assembly of Dendrimers
A R T I C L E S
Table 3. Association Constants for Dendritic Psuedorotaxane
Complexes, in Acetone-d6 at 22 °C
and ca. 3 days, respectively. Hec and Hdc appeared at 4.6 and
4.7 ppm in each case, and no uncomplexed NCH2 signals were
observed individually or by careful integration of the 3.4-4.4
ppm region (as was done with 1a/DB24C8 to detect ∼10% of
uncomplexed NCH2 species).
host/guest
system
10-2 × K (M-1
)
10-2 × K (M-1
)
10-2 × K (M-1
)
10-6 × K a (M-1
)
o
1
2
3
3/1a
4/1a
5/1a
1.6 ((0.5)b
2.5 ((0.6)c
2.4 ((0.4)e
0.65 ((0.13)b 0.67 ((0.26)b 0.70 ((0.64)d
1.4 ((0.2)c
2.8 ((0.2)e
2.1 ((0.6)c
2.3 ((0.3)e
7.4 ((4.8)d
15 ((6)d
The signals of Ha5, Hb3c, and Hc3c of [4]pseudorotaxanes 9
(Scheme 4) appear at 7.82, 7.51, and 7.78 ppm, respectively.
No signals assignable to uncomplexed aromatic moieties in [2]-
or [3]-pseudorotaxanes 7 or 8 were found. Recall that in the
model system 1a/DB24C8, the [3]pseudorotaxane 8a was ob-
served via Hb2u and Hc2u (Figure 5). The sharp singlet observed
for Ha5 and well-resolved doublets for Hbc and Hcc indicate that
these signals originate from a single species, confirming the
sole existence of the 1:3 complex 9c and the absence of the
[2]- or [3]-pseudorotaxane complexes 7c and 8c.
a Overall association constant for formation of [4]pseudorotaxane 9d or
9e from 1 mol of 1a and 3 mol of second or third generation dendron 4 or
5, respectively; Ko ) K1K2K3. b The molar ratios of 1a, 7c, and 8c were
determined by integration of Hau (7.96 ppm, 3H, 1a), Ha2 (7.76 ppm, 2H,
7c), and Ha3 (7.73 ppm, 2H, 8c); these comprise all of the uncomplexed
NCH2 moieties. The latter two signals ride atop the broad signal for
+
complexed NH2 and were integrated by the cut and weigh method. The
total concentration of uncomplexed NCH2 moieties was determined by
integration of Hdc + Hec (4.80-4.95 ppm) versus all benzylic OCH2 signals
(4.95-5.30 ppm, 6H: Hq and Ht, Scheme 2). From these parameters, [1a],
[7c], and [8c] were determined. From the known concentration of complexed
NCH2 moieties, [9c] was calculated by difference. The results from the
following initial concentrations of 1a/3 were used to evaluate K1, K2, and
K3: 10/30, 10/40, 10/50, 10/60 mM/mM. Error bars are the standard
deviations. c The extent of complexation of the dendron and NCH2 moieties
was determined by (1) integration of Hnu (5.26 ppm, 2H) versus all benzylic
Quantitative evidence of the exclusive formation of [4]-
1
pseudorotaxane dendrimers 9 came from integration of the H
NMR spectra. The ratios of integrals of the signals for Ha5
(Scheme 4) at 7.82-7.84 ppm versus those for Hdc + Hec at
4.7 and 4.5 ppm were 0.25, in accord with theory. This was
also true before equilibrium was reached, meaning that 1a
dissolves solely as the [4]pseudorotaxanes 9. In first generation
9c, the signals for Hdc, Hec, Hqc, and Htc (Schemes 2 and 4)
should integrate in the ratio of 2:2:2:4; indeed, the signals at
4.68, 4.57, 5.12, and 4.99 ppm (Figure 10) integrated in the
ratio 2.0:2.0:2.0:4.0, respectively. The stoichiometry of com-
plex from 1a and third generation dendron 5 was determined
to be 1:3 by integration of the signals for Hdc and Hec versus
complexed benzylic protons Hkc (Figure 11, Schemes 2 and 4).
The sole existence of the wholly complexed [4]pseudorotax-
ane dendrimer 9e was also demonstrated by the integrals of
signals for Ha5, Hkc, and Hdc + Hec protons in a 1.0:2.0:4.0
ratio.
OCH2 signals (4.9-5.3 ppm, 14H, Hn, Hq, and Ht, Scheme 2), (2) Hdc
+
Hec (ppm) versus all benzylic OCH2 signals, (3) Hdc + Hec (ppm) versus
aromatic protons Ho, Hp, Hr, Hs, Hw, Hy, and Hz (6.4-7.1 ppm, 14H, Scheme
2), and (4) integration of the doublet (J ) 8 Hz) for Hwu (7.00 ppm, 1H)
versus aromatic protons Ho, Hp, Hr, Hs, Hw, Hy, and Hz (6.4-7.1 ppm,
14H, Scheme 2). Integration of the pairs of signals for Hdu + Heu of 1a,
[2]- (7d), and [3]-pseudorotaxanes (8d) yielded the relative concentrations
of these species. The concentration of 1a was confirmed using the integration
of the Hau signal at ∼7.96 ppm. The concentration of the [4]pseudorotaxane
9d was determined by difference. The results from the following initial
concentrations of 1a/4 were used: for K1, from 10/10 to 10/30 mM/mM;
for K2 and K3, from 10/10 to 10/20 mM/mM. Error bars are the standard
deviations. d Error cited is average deviation from the nominal value
calculated using both the maximum and the minimum values for K1, K2,
and K3 based on the individual error bars. e The extent of complexation
was determined by integration of Hku (5.2 ppm, 2H) versus the aromatic
protons Hl, Hm, Ho, Hp, Hr, Hs, Hw, Hy, and Hz (6.4-7.0 ppm, 26H, Scheme
2). Integration of the pairs of signals for Hdu + Heu of 1a, [2]- (7e), and
[3]-pseudorotaxanes (8e) afforded the relative concentrations of these
species. The concentration of 1a was confirmed by integration of the Hau
signal at ∼7.96 ppm. The concentration of the [4]pseudorotaxane 9e was
determined by difference. The results from the following initial concentra-
tions of 1a/5 were used: for K1, from 10/10 to 10/20 mM/mM; for K2 and
K3, from 10/10 to 10/30 mM/mM. Error bars are the standard deviations.
Inasmuch as free tritopic guest 1a and [2]- and [3]-pseudoro-
taxanes 7 and 8 (Scheme 1) could not be detected in solutions
of crown-functionalized dendrons 3-5 and 1a in CDCl3, it was
not possible to calculate association constants. However, the
percentages of solid 1a dissolved in 30 mM solutions of the
dendrons serve as indicators of the relative Ka values for the
three [4]pseudorotaxane complexes 9c, 9d, and 9e. The amount
of 1a in a solution of dendron 3 was determined and cor-
roborated by three methods using the following integrals: (a)
generation dendrons 4 and 5. K1 for complexation of the
dendrons 3, 4, and 5 is less than that with DB24C8. This is
taken as a reflection of steric effects with the dendrons that are
eventually compensated through cooperative interactions which
increase K2 and K3 significantly for the dendrons relative to
DB24C8. This can be seen by the fact that Kave for 3 (97 M-1
is less than Ka for model ester crown 2b with monotopic guest
6a, but Kave for 4 and 5 are equal or greater.
In a solution of homotritopic guest 1a (10 mM) and third
generation dendron 5 (10 mM) at and below -20 °C no
uncomplexed dendron could be detected based on the Hku signal
(Scheme 2). Thus, at lower temperatures, formation of [4]-
pseudorotaxane 9e is complete. The second generation system
1a/4 behaved similarly, yielding only the self-assembled den-
drimer 9d.
B. In CDCl3. Dendrons 3 (Figure 10), 4,21 and 5 (Figure 11)
as 30 mM solutions were treated with solid homotritopic guest
1a (in an amount that corresponded to 10 mM if it completely
dissolved); equilibrium was reached after ca. 12 h, ca. 2 days,
)
Ha5 (7.84 ppm, 3H) versus the total for Hr, Hs, Hw, Hy, and Hz
(6.4-7.0 ppm, 8H), (b) Hqu (5.25 ppm, 2H) versus the total for
Hqu, Hqc, Htu, and Htc (4.9-5.4 ppm, 6H) of dendron 3, and (c)
Hdc + Hec (4.54 ppm, 12H) versus the total for Hqu, Hqc, Htu,
and Htc (4.9-5.4 ppm, 6H). After equilibration, 58.2 ((2.1)%
of 1a had dissolved, yielding a solution 5.82 ((0.21) mM in
total concentration of 1a, all of it in the form of [4]pseudoro-
taxane 9c. The amount of 1a taken into solution by 4 was
determined analogously; the final solution was 5.98 ((0.23)
mM in total concentration of 1a, all in the form of 9d. A total
of 66.6% of 1a ([9e] ) 6.66 ((0.30) mM) was taken into the
30 mM solution of third generation dendron 5; using a 10 mM
solution of 5 and an equivalent amount of solid 1a, the final
solution contained 2.25 ((0.12) mM of 9e. The latter concentra-
tion is 20% higher than the monotopic guest 6a (5.59 mM) in
(28) (a) Claissens, C. G.; Stoddart, J. F. J. Phys. Org. Chem. 1997, 10, 254-
272. (b) See: Cantrill, S. J.; Preece, J. A.; Stoddart, J. F.; Wang, Z.-H.;
White, A. J. P.; Williams, D. J. Tetrahedron 2000, 56, 6675-6681 for a
discussion of the importance of C-H- - -π bonds in crystals of tetrabenzo-
24-crown-8 and leading references to this phenomenon.
+
10 mM 5 (above) on a per NH2 basis. The larger crowned
dendrons are more effective hosts than the smaller ones. This
is consistent with cooperative binding of 5 by 1a.
9
J. AM. CHEM. SOC. VOL. 124, NO. 17, 2002 4663

A R T I C L E S
Gibson et al.
Figure 9. Scatchard plots for complexation of homotritopic guest 1a with (a) (left) first generation monotopic dendron 3, (b) (middle) second generation
monotopic dendron 4, and (c) (right) third generation monotopic dendron 5 in CD3COCD3 at 22 °C. p ) fraction of ammonium sites bound. Error bars in
p, (0.03 absolute; error bars in p/[host], (15% relative. The lines (second order polynomial fits) are simply to guide the eye.
Figure 10. The 1H NMR spectra (400 MHz, 22 °C) of (a) a 30 mM CDCl3
solution of first generation monotopic dendron 3; a 30 mM CDCl3 solution
1
of 3 mixed with /3 mol equiv of solid tritopic guest 1a after (b) 10 min
and (c) 15 h. The first letter and number of the subscript designate the
proton (see Schemes 2 and 4) and the second letter whether the signal
corresponds to uncomplexed (u) or complexed (c) species.
Figure 12. The MALDI-TOF mass spectrum (matrix: DHBA) of a sample
prepared by freeze-drying (-78 °C, in vacuo) a solution of homotritopic
guest 1a (2.50 mM) and third generation dendron 5 (7.50 mM) in acetone,
showing the presence of third generation dendritic [2]-, [3]-, and [4]-pseu-
dorotaxanes 7e, 8e, and 9e (Scheme 1), respectively.
CDCl3 to form a 1:1 complex containing three pseudorotaxane
moieties was reported.29 This may be termed “entropic coop-
erativity” since it involves bimolecular complexation of fairly
rigid complementary tritopic species. In contrast, the present
cooperativity appears to be more enthalpically driven in that it
involves four distinct molecules, three of which are very flexible,
interacting to form the [4]pseudorotaxanes 9c-e.
1
Figure 11. The H NMR spectra (400 MHz, CDCl3, 22 °C) of (a) a 30
1
mM solution of third generation monotopic dendron 5 mixed with /3 mol
equiv of solid homotritopic guest 1a recorded (a) immediately, (b) after 10
min, and (c) after 72 h. The first letter and number of the subscript designate
the proton (see Schemes 2 and 4) and the second letter whether the signal
corresponds to uncomplexed (u) or complexed (c) species.
C. Mass Spectrometry. The dendritic pseudorotaxanes were
analyzed by mass spectrometry using samples prepared by
freeze-drying acetone solutions of homotritopic guest 1a with
3 equiv of the dendrons 3, 4, and 5. In each case, the spectrum
(either FAB or MALDI-TOF) contains peaks for the self-
assembled dendritic [4]pseudorotaxane complex 9, [3]pseu-
The slower formation of third generation dendritic [4]-
pseudorotaxane 9e relative to the smaller dendrimers 9c and
9d is attributed to steric hindrance experienced by neighboring
dendron units. The latter can be deduced from the following
two spectroscopic observations. Significant upfield shifts were
observed for the complexed benzylic protons of third genera-
tion dendron 5: Hkc, Hnc, Hqc, and Htc in 9e (Figure 10). In
contrast, in the spectra of dendron 5 and monotopic guest 6a
(Figure 7), the signals for these benzylic protons in the
[2]pseudorotaxane complex 5:6a were indistinguishable from
those of uncomplexed 5.
-
dorotaxane 8, and [2]pseudorotaxane 7 after losses of PF6
counterions.21 In the case of the second generation system 4,
we note loss of HPO42-, a hydrolysis product of PF6 as
-
documented in the literature.30 Figure 12 shows the MALDI-
TOF MS for the third generation system 1a/5; peaks at intervals
of 91 mass units below [8e-2PF6]+ and [7e-2PF6]+ indicate loss
of benzyl groups from the periphery of the dendrons. The
(29) Fyfe, M. C. T.; Lowe, J. N.; Stoddart, J. F.; Williams, D. J. Org. Lett.
2000, 2, 1221-1224.
(30) Moucheron, C.; Kirsch-De Mesmaeker, A. J. Am. Chem. Soc. 1996, 118,
12834-12835.
Recently, a qualitative observation of cooperativity in the
binding of a homotritopic DB24C8 analogue by 1a in CD3CN/
9
4664 J. AM. CHEM. SOC. VOL. 124, NO. 17, 2002

Cooperative Self-Assembly of Dendrimers
A R T I C L E S
Table 4. Supramolecular Formulas, Calculated Supramolecular Weights, and Observed (MS) Mass/Charge Ratios
structure
molecular formula
calcd MW
obs m/z
9c-PF6
[C48H48N3P2F12(C46H50O12)3]+
[C48H48N3PF6(C46H50O12)2]+
[C48H48N3(C46H50O12)]+
3339.3
2400.0
1460.7
3339.5a1, 3344.6 d1
2400.2a2, 2400.8d2
1459.2a3, 1460.4d3
4611.06b1, 4612.5e1
3248.69b2, 3249.6e2
3318.42b3
8c-2PF6
7c-3PF6
9d-PF6
8d-2PF6
8d-3PF6 + Na + 2HPO4
7d-2PF6
7d-3PF6 + Na + 2HPO4
9e-PF6
8e-2PF6
8e-2PF6-C7H7
7e-2PF6 + H
7e-2PF6 + H-C7H7
[C48H48N3P2F12(C74H74O16)3]+
[C48H48N3PF6(C74H74O16)2]+
[C48H48N3(C74H74O16)2(Na)(HPO4)2]+
[C48H48N3PF6(C74H74O16)]+
4611.81
3248.34
3318.38
1884.88
1954.91
7156.81
4945.01
4853.96
2734.23
643.18
1884.90b4, 1884.3e3
1954.93b5
[C48H48N3(C74H74O16)(Na)(HPO4)2]+
[C48H48N3P2F12(C130H122O24)3]+
[C48H48N3PF6(C130H122O24)2]+
[C48H48N3PF6(C130H122O24)(C123H115O24)]+
[C48H48N3PF6(C130H122O24)]+
[C48H48N3PF6(C123H115O24)]+
7156.62c1
4945.03c2
4854.03c3
2734.18c4
2643.18c5
a FAB mass spectrum recorded in the positive ion mode using 3-NBA as the matrix; sample prepared by freeze-drying (-78 °C, in vacuo) an acetone
solution 5.00 mM in 1a and 15.00 mM in 3. (1) 5%, (2) 6%, (3) taken as base peak. b MALDI-TOF mass spectrum recorded in the positive ion mode using
trans-3-indoleacrylic acid (IAA) matrix; sample prepared by freeze-drying (-78 °C, in vacuo) an acetone solution 2.50 mM in 1a and 7.50 mM in 4. (1)
6%, (2) 32%, (3) 15%, (4) taken as base peak, (5) 90%. c MALDI-TOF mass spectrum recorded in the positive ion mode using 2,5-dihydroxybenzoic acid
(DHBA) as the matrix; sample prepared by freeze-drying (-78 °C, in vacuo) an acetone solution 2.50 mM in 1a and 7.50 mM in 5. (1) 9%, (2) 31%, (3)
8%, (4) taken as base peak, (5) 17%. d MALDI-TOF mass spectrum recorded in the positive ion mode using DHBA as the matrix; sample prepared as noted
above. (1) 4%, (2) 15%, (3) 62% of base peak at m/z ) 666.0 [1a - 2PF6 - HPF6]+. e MALDI-TOF mass spectrum recorded in the positive ion mode using
DHBA as the matrix; sample prepared as noted above. (1) 0.7%, (2) 2%, (3) 44% of base peak at m/z ) 559.2 [1a - 2PF6 - HPF6 - C6H5CH2NH2]+.
apparent distribution of the complexes indicates partial dis-
sociation/fragmentation of 9e into subunits 8e and 7e during
ionization or in the relatively polar matrix. The calculated and
observed masses (<0.1% error) of the dendritic pseudorotaxanes
are summarized in Table 4.
plications in addition to those of current interest with covalent
dendrimers.3-9
Experimental Section
1
400 MHz H NMR spectra were recorded on a Varian Unity with
tetramethylsilane (TMS) as an internal standard. Mass spectra were
provided by the Nebraska Center for Mass Spectrometry, Lincoln,
Nebraska, and also by the Washington University Mass Spectrometry
Resource, an NIH Research Resource (grant no. P41RR0954). 1,3,5-
Tris[p-(benzylammoniomethyl)phenyl]benzene tris(hexafluorophos-
phate) (1a) was prepared according to the literature,18,20 as was
dibenzylammonium hexafluorophosphate (6a).19
Conclusions
In acetonitrile and acetone, in which triammonium salt 1a is
soluble, it was possible to detect [2]-, [3]-, and [4]-pseudoro-
taxane complexes 7a, 8a, and 9a of DB24C8 distinctly by H
1
NMR spectroscopy and to estimate association constants. In
complexation with DB24C8, the three ammonium sites of 1a
act independently, and hence the three association constants
follow the expected statistical ratios. These are believed to be
the first association constants measured for [4]-pseudorotaxanes.
The nearly exclusive (∼90%) formation of the [4]pseudorotax-
ane 9a from the insoluble trisalt 1a in chloroform is noteworthy.
Mass spectrometry was also used to characterize the pseudoro-
taxanes.
Acknowledgment. The authors gratefully acknowledge fi-
nancial support by the Chemistry Division of the National
Science Foundation through award CHE-9521738 and the
Petroleum Research Fund administered by the American
Chemical Society (grants 3119-AC7 and 33518-AC7). We are
also grateful to Mr. Tom Glass of this Department for his able
advice and assistance with regard to the NMR experiments.
We then demonstrated a concise design and efficient self-
assembly of pseudorotaxane dendrimers 9c-e. In acetone-d6,
complexations of crown functionalized dendrons 3-5 with
homotritopic guest 1a are positiVely cooperatiVe. Furthermore,
the larger dendrons displayed increased association constants.
This effect is attributed to encapsulation of the ionic core of
the triammonium salt, resulting in screening of the charges from
the nonpolar bulk solvent. In chloroform-d, dendritic [4]-
pseudorotaxanes 9c-e are exclusiVely formed as a result of
positiVely cooperatiVe binding.
This and related positively cooperative self-assembly ap-
proaches offer the possibility of generating larger and more
complex supramolecular structures. Encapsulation of guests
during the self-assembly process is also an interesting possibility,
especially coupled with pH control of this type of reversible
pseudorotaxane formation,31 suggesting several types of ap-
Supporting Information Available: Procedures for synthesis
of 6b and 1b, table of 1H NMR signal assignments for DB24C8/
1a in CD3CN, 1H NMR and mass spectra (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
JA012155S
(31) Ashton, P. R.; Ballardini, R.; Balzani, V.; Gomez-Lopez, M.; Lawrence,
S. E.; Martinez-Diaz, M. V.; Montalti, M.; Piersanti, A.; Prodi, L.; Stoddart,
J. F.; Williams, D. J. J. Am. Chem. Soc. 1997, 119, 10641-10651. Ashton,
P. R.; Ballardini, R.; Balzani, V.; Baxter, I.; Credi, A.; Fyfe, M. C. T.;
Gandolfi, M. T.; Gomez-Lopez, M.; Martinez-Diaz, M.-V.; Morosini, M.;
Piersanti, A.; Spencer, N.; Stoddart, J. F.; Venturi, M.; White, A. J. P.;
Williams, D. J. J. Am. Chem. Soc. 1998, 120, 11932-11942. Balzani, V.;
Gomez-Lopez, M.; Stoddart, J. F. Acc. Chem. Res. 1998, 31, 405-414.
Ishow, E.; Credi, A.; Balzani, V.; Spadola, F.; Mandolini, L. Chem.-Eur.
J. 1999, 5, 984-989. Balzani, V.; Credi, A.; Venturi, M. In Stimulating
Concepts in Chemistry; Vo¨gtle, F., Stoddart, J. F., Shibasaki, M., Eds.;
Wiley-VCH: New York, 2000; pp 255-266. Balzani, V.; Credi, A.;
Raymo, F. M.; Stoddart, J. F. Angew. Chem., Int. Ed. 2000, 39, 3349-
3391. Stoddart, J. F. Acc. Chem. Res. 2001, 34, 410-411.
9
J. AM. CHEM. SOC. VOL. 124, NO. 17, 2002 4665