Self-assembly of hybrid dendrons into doubly segregated supramolecular polyhedral columns and vesicles

Article abstract of DOI:10.1021/ja104432d

The synthesis and structural analysis of supramolecular dendrimers self-assembled from 3 libraries containing 20 first-generation hybrid dendrons are reported. Combinations of benzyl ether, naphthyl methyl ether, and biphenyl methyl ether repeat units wit

Full text of DOI:10.1021/ja104432d

Published on Web 07/22/2010
Self-Assembly of Hybrid Dendrons into Doubly Segregated
Supramolecular Polyhedral Columns and Vesicles
Mihai Peterca,†,‡ Mohammad R. Imam,†,§ Pawaret Leowanawat,† Brad M. Rosen,†
Daniela A. Wilson,† Christopher J. Wilson,† Xiangbing Zeng,| Goran Ungar,|
Paul A. Heiney,‡ and Virgil Percec*,†
Roy & Diana Vagelos Laboratories, Department of Chemistry, and Department of Physics and
Astronomy, UniVersity of PennsylVania, Philadelphia, PennsylVania 19104, and Department of
Engineering Materials, UniVersity of Sheffield, Sheffield S1 3JD, United Kingdom
Received May 21, 2010; E-mail: percec@sas.upenn.edu
Abstract: The synthesis and structural analysis of supramolecular dendrimers self-assembled from 3 libraries
containing 20 first-generation hybrid dendrons are reported. Combinations of benzyl ether, naphthyl methyl
ether, and biphenyl methyl ether repeat units with different alkyl carboxylates at the apex of the dendron
decreased its molecular solid angle to values that led to the discovery of a new mechanism of self-assembly.
This new self-assembly mechanism generated a diversity of unprecedented supramolecular assemblies, including
hollow and nonhollow singly or doubly segregated supramolecular columns and vesicles exhibiting polyhedral
shapes. The polyhedral shape of the self-organized supramolecular dendrimers was demonstrated to be an
intrinsic characteristic of all the doubly segregated structures. The self-assembly mechanism elucidated here
provides access to new strategies that will be used to fabricate complex supramolecular organizations.
1. Introduction
are monodisperse macromolecules that form a variety of
complex periodic or quasi-periodic spatial organizations.5 These
organizations are determined by their specific primary structure
and are dependent on the environmental conditions. Self-
assembling dendritic structures have impacted the field of
supramolecular nanoscience6 with applications ranging from
supramolecular capsules,7 vesicles,8 porous protein mimics,9 and
ion channels10 to molecular actuators11 and organic electronic
materials.12 Establishing general principles that correlate the
dendritic primary structure with the resulting supramolecular
structure in the self-organized state is essential not only for the
design of building blocks that provide new functions, but also
Self-assembling dendrons1 and dendrimers,2 synthesized via
iterative convergent,3 divergent,4 or combined methodologies,
† Department of Chemistry, University of Pennsylvania.
‡ Department of Physics and Astronomy, University of Pennsylvania.
§ Current address: Department of Chemistry, King Fahd University of
Petroleum & Minerals (KFUPM), Dhahran 31261, Saudi Arabia.
| University of Sheffield.
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10.1021/ja104432d  2010 American Chemical Society

Self-Assembly of Hybrid Dendrons
A R T I C L E S
Scheme 1. Synthesis of Periphery Groups of the Hybrid Dendrons
for the understanding of similar organizations observed in
biological structures.13
powder diffractions of any other type of polyhedral domain.
New structural characterization techniques were also developed
to calculate the number of dendrons forming the inner and outer
layers of the doubly segregated assemblies. The dependence
Classes of dendritic structures were recently shown to self-
assemble into bicontinuous cubic phases,14 triple-network cubic
phases,15 supramolecular porous columns,9 and hollow spheres7c
with a hollow center ranging from a few angstroms to a few
nanometers. The formation of hollow supramolecular assemblies
was correlated with the decrease of the solid angle of the
dendron.7c,9 On the other hand, the process of self-assembly of
dendritic structures into a variety of bicontinuous cubic phases
is not well understood. This process was mostly correlated with
the primary structure of the self-assembling dendron.5,16,17
Encapsulation and selective transport of larger molecular guests
require a further increase of the size of the hollow regions.
Considering that these empty regions can have a significant
penalty to the value of the free energy, constructing larger
hollow centers is problematic. Furthermore, increasing the size
and complexity of the supramolecular assemblies, without
increasing the complexity of the building block, represents a
considerable challenge. Here we report the engineering of the
solid angle of the dendron16 through the synthesis of first-
generation hybrid self-assembling dendrons based on combina-
tions of benzyl ether, naphthyl methyl ether, and biphenyl methyl
ether repeat units and different alkyl carboxylates at the apex.
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Using reconstruction of the electron density distributions and
analysis and simulation of the powder X-ray diffractograms, in
combination with molecular modeling, we establish that the self-
assembly of dendrons follows either the traditional singly
segregated aliphatic-aromatic route1,5 or a new doubly segre-
gated aliphatic-aromatic-aliphatic route.17 The differentiation
between the two pathways followed by the self-assembly process
is correlated with the dendron solid angle, the structure of the
apex building block, and the addition of branching points in
the alkyl chains. New methodologies based on the analytical
calculation of the Fourier transform of the polyhedral domains
were developed to facilitate complete structural analysis of the
singly and doubly segregated columnar phases. For the cubic
phases, the powder X-ray data simulations involved numerical
multidimensional integration over polyhedral domains generated
by a new method called “scaled Voronoi tessellation”. This
method is general and can be easily modified to simulate X-ray
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Scheme 2. Synthesis of Hybrid Dendrons
between the primary structure of self-assembling dendrons and
their supramolecular structure was expanded to include the
doubly segregated columnar and cubic phases. These correla-
tions were also used to elucidate the omnipresent polyhedral
shape of the doubly segregated supramolecular assemblies.
Structural analysis demonstrates the first example of a hollow
dendritic “bulk” vesicle assembled from 1012 dendrons.
CH2OH.9h Synthesis began with the construction of the benzyl
chlorides that will decorate the periphery of the dendrons. (4)12G0-
CH2Cl,19 (6Np)12G0-CH2Cl,20 and (4Bp)12G0-CH2Cl20 were
prepared according to literature procedures. (6Np)dm8*G0-CH2Cl
was prepared in three steps from methyl 6-hydroxy-2-napthoate
(Scheme 1, top).
Alkylation of methyl 6-hydroxy-2-napthoate with (S)-1-
bromo-2,7-dimethoxyoctane in DMF in the presence of K2CO3
as a base provided (6Np)dm8*G0-CO2CH3 in 90% yield.
Reduction with LiAlH4 in THF (97% yield) followed by
chlorination with SOCl2 in CH2Cl2 (91% yield) produced
(6Np)dm8*G0-CH2Cl. (4Bp)dm8*G0-CH2Cl and (4Bp)Et6G0-
CH2Cl were prepared similarly to (6Np)dm8*G0-CH2Cl (Scheme
2, bottom). Methyl 4′-hydroxy-4-biphenylcarboxylate was alky-
lated with (S)-1-bromo-2,7-dimethoxyoctane or 2-ethylhexyl
2. Results and Discussion
2.1. Synthesis of Hybrid Dendrons. The three libraries of
hybrid dendrons reported in this paper (Schemes 1 and 2) were
synthesized according to convergent methods reported previ-
ously for the preparation of (4-3,4)12G1-CO2CH3,18 (4-3,4)12G1-
CH2OH,18 (6Np-3,4)12G1-CO2CH3,9h and (6Np-3,4)12G1-
(16) Ungar, G.; Percec, V.; Holerca, M. N.; Johansson, G.; Heck, J. A.
Chem.sEur. J. 2000, 6, 1258–1266.
(19) Percec, V.; Ahn, C.-H.; Chow, W.-D.; Jamieson, A. M.; Kim, J.;
Leman, T.; Schmidt, M.; Gerle, M.; Mo¨ller, M.; Prokhorova, S. A.;
Sheiko, S. S.; Cheng, S. Z. D.; Zhang, A.; Ungar, G.; Yeardley, D. J. P.
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Huang, C.; Lipski, L. R.; Zeng, X.; Ungar, G.; Heiney, P. A.; Percec,
V. J. Am. Chem. Soc. 2009, 131, 17500–17521.
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10273–10281.
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Macromolecules 1998, 31, 1745–1762.
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A R T I C L E S
Figure 1. Small-angle powder XRD data collected in the columnar hexagonal (a) and cubic (b) phases self-organized from hybrid dendrons. The data are
scaled to the (10) diffraction peak intensity for columnar and to the (210) diffraction peak intensity for cubic phases. The temperature at which the XRD data
were recorded, the corresponding phase, and the lattice dimensions are indicated. In (a) the intensity profiles of the dendritic alcohols provide the reference
for the increase of the relative intensity of the diffraction peaks with qhk > q10 observed for the dendritic esters. In (b) the gray dotted rectangles indicate the
diffraction peaks with unusual relative intensity.
bromide in DMF in the presence of K2CO3 base, giving
(4Bp)dm8*G0-CO2CH3 and (4Bp)Et6G0-CO2CH3 in 91-95%
yield. Reduction with LiAlH4 in THF (88-94% yield), followed
by chlorination with SOCl2 in CH2Cl2 (89-97%), produced
(4Bp)dm8*G0-CH2Cl and (4Bp)Et6G0-CH2Cl.
that self-organize into a variety of 2-dimensional or 3-dimen-
sional periodic arrays (Figures 1-3 and Table 1; Figures SF1
and SF2 and Tables ST1 and ST2, Supporting Information).
The general trend observed for the dendritic esters is illustrated
in Figure 2 and indicates that the addition of one or two
methylenic groups to their apexes significantly changes the self-
assembly process. For all the benzyl ether, naphthyl methyl
ether, and biphenyl methyl ether based dendrons containing an
ester group at the apex (Scheme 2), this addition induces the
Achiral and chiral generation one dendrons with esters at the
apex were synthesized via the alkylation of nonbranched
peripherygroups(Scheme2,purple),(4)12G0-CH2Cl,(6Np)12G0-
CH2Cl, (6Np)dm8*12G0-CH2Cl, (4Bp)12G0-CH2Cl, (4Bp)-
dm8*12G0-CH2Cl, or (4Bp)Et6G0-CH2Cl, onto branched apex
groups (Scheme 2, orange), methyl 3,4-dihydroxybenzoate,
methyl 2-(3,4-dihydroxyphenyl)acetate, or methyl 3-(3,4-dihy-
droxyphenyl)propanoate, in DMF in the presence of K2CO3 as
a base. Reduction of the generation one dendrons with esters at
the apex with LiAlH4 in THF produced the corresponding
dendritic alcohols. One selected dendritic ester, (4Bp-3,4)12G1-
CO2CH3, was saponified with KOH in hot EtOH-THF to
provide (4Bp-3,4)12G1-CO2H in 92% yield. (4Bp-3,4)12G1-
CO2CH2CH2OCH3 was prepared in 70% yield via Mitsunobu
esterification of (4Bp-3,4)12G1-CO2H with 2-methoxyethanol
in the presence of diisopropyl azodicarboxylate (DIAD) and
PPh3.
j
formation of a high-temperature Pm3n cubic phase. Furthermore,
the hybrid biphenyl methyl ether dendrons exhibit a jump of
the diameter of the supramolecular column of their hexagonal
phases equal to ahex[(4Bp-3,4Pr)12G1-CO2CH3] - ahex[(4Bp-
3,4)12G1-CO2CH3] ) 84.0 - 69.1 Å ) 14.9 Å. At the same
time, the relative intensity of the higher order diffraction peaks
of the columnar hexagonal and cubic phases exhibit an unusual
enhancement (Figure 1). For example, the relative intensity of
the (20) diffraction peak of the hexagonal phase of (4Bp-
3,4)12G1-CH2OH indicated in Figure 1a is area(20)/area(10)
) 0.05, whereas for (4Bp-3,4)12G1-CO2CH3 this ratio increases
j
to area(20)/area(10) ) 0.77 (Figure 1a). In the case of the Pm3n
cubic phases indicated in Figure 1b, the relative intensity of
the (321) diffraction peak of (4Bp-3,4Pr)12G1-CO2CH3 is
area(321)/area(210) ) 2.4.
2.2. Structural and Retrostructural Analysis. Structural
analysis, performed via a combination of differential scanning
calorimetry, polarized optical microscopy, small- and wide-angle
X-ray powder and oriented fiber diffraction experiments, and
experimental density measurements,1a,b,d,g-i,q,s,t demonstrated
that all dendrons self-assemble in supramolecular dendrimers
Recently,1s it was shown that a small enhancement of the
higher order diffraction peaks’ relative intensity can be generated
by the variation of the dendron alkyl chain length. For example,
the ratio area(321)/area(210) varied from <0.01 for the dendrons
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Peterca et al.
change of the alkyl periphery from hydrogenated to fluorinated
chains.1r These two examples illustrate a variety of factors that
can influence the relative intensity of the higher order diffraction
peaks. In the case of supramolecular dendritic hollow structures
j
self-organized into Pm3n cubic phases, the ratio area(321)/
area(210) was at most 0.8,7c which is roughly only one-third
of what is observed for the structures shown in Figure 1b.
Therefore, the substantial increase in the relative intensity of
the higher order diffraction peaks, from 0.11 to 0.8, was
previously associated with the presence of a hollow center.7c,9
As will be shown later, the polyhedral shape of the supramo-
lecular structures self-organized into the bilayer columnar and
cubic phases provides an additional factor that contributed to
the amplifications illustrated in Figure 1.
In contrast with the majority of dendrons that self-organize
in hexagonal and cubic phases, all the structures with 3,4Et and
3,4Pr apexes exhibit an unusual trend: the lattice dimension of
the cubic phase is much larger than the expected value, which
must be double that of the hexagonal phase7c (Table 1, Figure
2). This correlation, 2ahex ≈ acub, is expected as long as the
supramolecular structures preserve their diameter and their
internal organization upon the shape change from supramo-
lecular columns to supramolecular spheres. For example, in the
case of (4-3,4Et)12G1-CO2CH3 and (4Bp-3,4Pr)12G1-CO2CH3
dendritic esters the expected7c lattice parameters of the cubic
phases, 2ahex, are 86.2 and 168.0 Å, respectively. The experi-
mental values of acub ) 159.4 and 221.5 Å are, respectively,
85% and 32% larger than the expected dimensions. This
observation coupled with the significant enhancement of the
higher order diffraction peaks observed for both cubic and
hexagonal phases (Figure 1) is the first indication that these
structures follow different self-assembly routes upon the first-
order transition from hexagonal to cubic phases.
Figure 2. Fully extended molecular models of the first-generation dendrons
containing their aliphatic tails in the all-trans conformation indicating the
maximum possible length of the dendron, L. In all cases the column
diameters, Dcol, of the hexagonal phases observed from the corresponding
dendritic alcohols are given in square brackets. LC ) liquid crystal columnar
phase. The values marked by a shaded yellow background correspond to a
doubly segregated aliphatic-aromatic-aliphatic phase.
containing 14 and 16 C atoms in their alkyl periphery to at most
0.11 for the dendrons containing 6 C atoms in their alkyl
periphery.1s More significant changes of the powder diffraction
The second result that suggests a different pathway of the
self-assembly process is extracted from the analysis of the wide-
angle X-ray scattering (WAXS) patterns collected from oriented
fibers1q in the columnar hexagonal phase. Figure 3 shows that
the larger-than-expected hexagonal phases, observed for the
j
intensity profile collected from Pm3n cubic phases self-
organized from dendritic structures were observed previously
upon isomorphous replacement of the apex group and upon the
Figure 3. WAXS patterns collected from the oriented fibers of the indicated hybrid dendrons (a-f). Small-angle powder XRD data for the compounds from
(c) and (d) and of the hybrid dendritic alcohol (4Bp-3,4)12G1-CH2OH at corresponding temperatures (g).
9
11292 J. AM. CHEM. SOC. VOL. 132, NO. 32, 2010

Self-Assembly of Hybrid Dendrons
A R T I C L E S
Table 1. Structural and Retrostructural Analysis of the Libraries of First-Generation Hybrid Dendrons
d10, d11, d20, d21, d30 (Å);d
d001, d002, d003, d004 (Å);e
d200, d210, d211, d321, d400, d420 (Å);f
d20, d11, d31, d40, d02, d22 (Å)g
shape of the
supramolecular
structureb
j
F
γm
compd
T (°C) phasea
a, bc (Å)
Mh ti (Å) (g/cm3)
µk
µcl (deg)
io
(4-3,4)12G1-CO2CH3
30 Φh
57.2
49.6, 28.6, 24.8, 18.7
49.8, 28.7, 24.9, 18.8
45.7, 22.8
717 3.5 1.0 p
8
56 Φh
57.4
45.7
159.4
n
(4-3,4Et)12G1-CO2CH3
(4-3,4Pr)12G1-CO2CH3
(6Np-3,4)12G1-CO2CH3
20 Lk
731
745
817
1.0p
1.0p
1.08
j
55 Pm3n Polyh-B
45 Φr-c
79.9, 71.5, 65.2, 42.7, 39.9, 35.7
442 19
132.1, 52.2 66.1, 48.6, 33.7, 33.0, 26.1, 24.3
68.4
65.4
o
-10 Lk
56.0
42.2
43.1
50.3
155.9
63.7
56.1, 28.0, 18.7
36.6, 21.1, 18.3
37.4, 21.6, 18.7, 14.1
50.3, 25.2
77.9, 69.7, 63.7, 41.7, 38.9, 34.9
55.2, 31.9, 27.6
q
o
o
-10 Φh
50 Φh
30 Lk
Polyh
Polyh
4.5
4.5
6
n
j
60 Pm3n Polyh-B
50 Φh
382 17
12
30 Φr-c
124.8, 57.2 62.6, 52.2, 33.7, 31.2, 28.6, 26.0
-6 Lk
57.4
50.2
55.4
61.7
66.7
56.6
65.9
171.2
57.4, 28.7, 19.1, 14.3
50.2, 25.1
55.4, 27.7, 18.5
53.6, 30.8, 26.7
58.0, 33.5, 28.9, 21.9
56.6, 28.3, 18.9
45
L
n
25 Lk
70 Φh
io
o
Polyh-H
Polyh-B
3.5
8
12
(6Np-3,4)dm8*G1-CO2CH3
(6Np-3,4Et)12G1-CO2CH3
100 Φh
761 3.5 1.08p
30
L
831
1.08p
80 Φh
Polyh-B
57.2, 32.9, 28.6
85.6, 76.6, 69.9, 45.8, 42.8, 38.3
4.5
13
490 20
j
90 Pm3n Polyh-B
70 Φr-c
136.2, 55.4 68.2, 51.8, 35.2, 34.1, 27.7, 25.7
67.9
-20 Lk
30 Lk
56.4
58.2
50.3
68.3
175.3
69.1
56.4, 28.2, 18.8
58.2, 29.1, 19.4
50.3, 25.2
59.4, 34.1, 29.5
87.6, 78.4, 71.6, 48.6, 43.8, 39.2
59.9, 34.5, 29.9, 22.6, 19.9
36.9
(6Np-3,4Pr)12G1-CO2CH3
845
1.08p
60
L
90 Φh
Polyh-B
95 Pm3n Polyh-B
4.5
14
518 21
10
j
io
(4Bp-3,4)12G1-CO2CH3
(4Bp-3,4Et)12G1-CO2CH3
35 Φh
150 Φx
30 Lk
Polyh-H
869 3.5 1.08
60.6
60.6, 30.3, 20.2
883
1.115
115 Φr-c
167.8, 58.3 84.5, 55.2, 40.2, 42.2, 29.2, 27.5
70.8
64.2
135 Φh
Polyh-B
81.5
70.8, 40.8, 35.3, 26.6
4.6
20
876 30
j
145 Pm3n Polyh-B
209.6
104.8, 93.7, 85.6, 56.0, 52.4, 46.9
1.08p
1.109
o
(4Bp-3,4Et)dm8*G1-CO2CH3
(4Bp-3,4Pr)12G1-CO2CH3
5
Φr-c
104.3, 50.4 52.4, 45.4, 28.6, 26.1, 25.2, 22.7 827
90 Lk
130 Pm3n Polyh-B
25 Lk
44.7
173.8
63.2
44.7, 22.3
86.9, 77.7, 70.9, 46.4, 43.4, 38.9
63.2, 31.6, 21.1, 15.8
j
4.6
4.6
516 22
897
110 Φr-c
170.8, 62.4 85.9, 58.7, 41.9, 42.7, 31.1, 29.3
69.9
130 Φh
Polyh-B
84.0
72.9, 41.9, 36.3, 27.5
21
1012 33
10
j
145 Pm3n Polyh-BH 221.5
110.7, 99.1, 90.4, 59.2, 55.4, 49.5
60.2, 34.7, 30.1, 23.2, 20.0
io
(4Bp-3,4)12G1-CO2CH2CH2OCH3
(4Bp-3,4)Et6G1-CO2CH3
25 Φh
125 Φr-c
150 Φx
30 Φr-c
125 Pm3n Polyh-B
95 Φh Polyh
Polyh-H
69.4
913 3.5 1.1p
159.0, 63.7 79.7, 59.2, 40.8, 39.7, 31.9, 29.6
36.8
79.8, 58.2 39.9, 47.2, 24.2, 19.9, 29.1, 23.5 757
68.2
53.9
1.1p
o
Polyh
j
139.2
56.1
69.8, 62.2, 56.7, 37.2, 34.8, 31.1
48.7, 28.0, 24.3
298 16
11
4.6
a Phase notation: Φh, columnar hexagonal phase; Φr-c, centered rectangular columnar phase; Pm3n, cubic phase; L, lamellar phase; Lk, ordered
j
o
io
lamellar phase; Φh , ordered columnar hexagonal phase; Φr-co, ordered centered rectangular columnar phase; Φx, unidentified columnar phase; Φh
,
columnar hexagonal phase with intracolumnar order. b Shape and internal structure of the supramolecular structure: Polyh, singly segregated polyhedral
cluster; Polyh-H, hollow singly segregated polyhedral structure; Polyh-B, doubly segregated polyhedral structure; Polyh-BH, hollow doubly segregated
polyhedral structure. c Lattice parameters calculated using a ) (2/ꢀ3)(d10 + (ꢀ3)d11 + 2d20 + (ꢀ7)d21)/4 for hexagonal phases, a ) (d001 + 2d002)/2 for
j
lamellar phases, a ) (2d200 + (ꢀ5)d210 + (ꢀ6)d211)/3 for Pm3n cubic phases, and a ) (2d20 + 4d40)/2 and b ) 2d02 for centered rectangular columnar
f
phases. d d-spacing for columnar hexagonal phases. e d-spacing for lamellar phases. d-spacing for Pm3n cubic phases. g d-spacing for centered
j
rectangular columnar phases. h Molecular weight. i Average column stratum thickness calculated within a range of (0.2 Å from the WAXS patterns.
k
j Experimental density at 20 °C. Number of dendrons per supramolecular column stratum or cluster calculated using µ ) (a2t(ꢀ3)/2)FNA/M for
hexagonal phases and µ ) (a /8)FNA/M for Pm3n cubic phases, where NA ) 6.022 × 1023 mol-1 ) Avogadro’s number. l Number of dendrons in the
3
j
m
2
j
b b
cross-section of the supramolecular clusters of the Pm3n cubic phase calculated using µ ) (πa t/16)FNA/M. Angle defined by γ ) ∠(ba+b, b) and
calculated using γ ) tan-1(a/b). n Phase observed only in the first heating cycle of the as-prepared compound. o Phase observed only in the cooling
p
cycle at 10 °C/min. Density values were assumed to be 1.0 g/cm3 for the benzyl ether library. For the naphtyl methyl ether and biphenyl methyl ether
libraries, the experimental values available for selected structures were assumed for the other structure of the corresponding library. q Phase observed
only in the cooling cycle at 1 °C/min.
hybrid biphenyl methyl ether dendritic esters, are liquid crystals.
Therefore, the enhancement of the higher order diffraction peaks
of the columnar hexagonal phases (Figures 1 and 3g) was not
generated by intracolumnar correlations. Such an effect, related
to possible dendron tilt correlations, has been observed in the
self-assembly of (4-3,4Et)12G1-CO2CH3 and will be discussed
cubic phases the self-assembly process follows the “traditional”
single aliphatic-to-aromatic microphase segregation,1a,r,s from
molecular modeling and experimental lattice parameters we find
that the supramolecular structures must have unusually large
empty domains (Supporting Information, Figure SF4). The
diameters of the empty regions are large enough to accommodate
at least one dendron with dimensions corresponding to the fully
j
in an another subsection. Assuming that in the observed Pm3n
9
J. AM. CHEM. SOC. VOL. 132, NO. 32, 2010 11293

A R T I C L E S
Peterca et al.
Scheme 3. Schematic Representation of the Self-Assembly of
Dendrons into Bilayer Structures
Figure 4. Second heating (black lines) and cooling (gray lines) differential
scanning calorimetry traces (both recorded at 10 °C/min) collected from
biphenyl methyl ether hybrid dendrons. The compound, phases, transition
temperatures (°C), and associated enthalpy changes (in parentheses, kcal/
mol) are indicated.
extended all-trans conformation shown in Figure 2. The self-
assembly process of the first-generation hybrid dendritic esters
is driven by weak interactions. In the absence of stronger
interactions, such as H-bonding7c,9 or ionic, the noncovalent
interactions are not strong enough to sustain a very large hollow
core. As will be shown later, this hollow region confers a
significant penalty to the free energy of the system. Therefore,
the most probable model supported by electron density recon-
structions, powder X-ray diffraction simulations, experimental
lattice parameters, and molecular modeling consists of the
doubly segregated aliphatic-aromatic supramolecular structure
illustrated in Scheme 3. This model fills completely or reduces
the diameter of the large hollow cavity shown in Figure SF4
and Scheme 3.
) (2 + x)ahex, with x ranging from 0.44 to 1.69 (Figure 2), can
be explained by the alternative pathways of self-assembly at
the transition from either singly or doubly segregated columns
to doubly segregated vesicles.
The mechanism shown in Scheme 3 resembles the assembly
of biological vesicles in dilute solutions.8,13 In the case of the
dendritic vesicles, the aliphatic-aromatic segregation replaces
the biological vesicle hydrophobic-hydrophilic segregation.
Nevertheless, the underlying mechanism that generates the two
segregations is completely different. In biological vesicles the
interaction with water generates the hydrophobic-hydrophilic
segregation and their formation, whereas in the dendritic vesicles
the double segregation is mediated by the dendron-dendron
interactions (Scheme 3).
2.3. Analysis of the Hexagonal Phases Self-Organized
from Polyhedral Supramolecular Columns. A closer inspection
of the intensity profiles of the small-angle X-ray powder
diffraction data summarized in Figure 1, and of the DSC traces
for selected biphenyl methyl ether dendritic esters shown in
Figure 4, reveals the complexity of the self-assembly and self-
organization process. The intensity profiles of the cubic phases
reported in Figure 1b exhibit a gradual increase of the relative
intensity of the higher order diffraction peaks. This enhancement
follows the increase of the lattice dimension, as well as the
change of the aromatic structure from benzyl ether to naphthyl
methyl ether and to biphenyl methyl ether. The most significant
change is observed in the biphenyl methyl ether case. With the
exception of (4-3,4Et)12G1-CO2CH3, the intensity profiles of
the XRD data collected in the columnar hexagonal phases shown
in Figure 1a follow a similar trend. The largest increase is again
observed upon the change from naphthyl methyl ether to
biphenyl methyl ether based dendrons with 3,4Et and 3,4Pr
groups at their apexes.
To understand the mechanism for the formation of doubly
segregated clusters, we imagine splitting the self-assembly
process into two stages. The addition of one or two methylenic
units to the carboxylate group from the apex of the dendron
reduces its solid angle.16 In the first stage, these “sharp”
dendrons are expected to self-assemble into large structures with
small curvature, which in turn forms the outer layer (Scheme
3). In the second stage, because the outer layer has an unusually
large diameter, the system can further minimize the free energy
by filling the empty region with a second layer of dendrons.
For clarity, the inner layer is shown in Scheme 3 with the
aromatic region colored in yellow. If we combine these two
stages, we form an outer layer with small curvature and an inner
layer that interdigitates with the outer larger one to further
maximize the layer-to-layer interactions. This mechanism,
illustrated in Scheme 3, does not contradict the segregation of
the aliphatic and aromatic regions. At the same time, the
proposed interdigitated mechanism is supported by the fact that
none of the dendritic alcohols investigated so far self-assemble
into an interdigitated cubic or bilayer hexagonal phase (Tables
ST1 and ST2, Supporting Information). In these structures, the
addition of strong apex-to-apex H-bonding interactions, for
example, via apex alcohol groups, prohibits the formation of
the interdigitated packing of the bilayer aromatic region.
Similarly, potential bilayer cubic phases were identified in the
previously published higher generation dendritic esters (4Bp-
2.3.1. Powder X-ray Diffraction Phase Problem for
Hollow and Nonhollow Polyhedral Columns. We have suggested
that the formation of the supramolecular assemblies self-
organized in the observed cubic phases must follow a doubly
segregated self-assembly process. Janus dendrimers, function-
alized with perfluorinated chains on one side and hydrogenated
1h
3,4Bp-3,5Bp)12G2-CO2CH3 and (4BpPr-3,4BpPr-3,5BpPr)-
12G2-CO2CH3.17 By contrast, no cubic phase was observed in
the corresponding dendritic alcohols.1h,17 In addition, the large
variation of the correlation between the lattice parameters, acub
9
11294 J. AM. CHEM. SOC. VOL. 132, NO. 32, 2010

Self-Assembly of Hybrid Dendrons
A R T I C L E S
chains on the other, were reported to self-assemble into
supramolecular bilayer columns.21 In these structures, the self-
assembly process into bilayer columns followed a perfluorinated
aromatic-aliphatic segregation. Molecular modeling combined
with the analysis of the lattice dimensions of the columnar
hexagonal phases (Supporting Information, Figure SF4) sug-
gested that the (4Bp-3,4)12G1-CO2CH3 and (4Bp-3,4Pr)12G1-
CO2CH3 hybrid dendrons may have empty core diameters, Dcore
,
of at least 14 and 27 Å, respectively. Previously,7c,9 enhanced
higher order diffraction peaks were associated with the presence
of hollow centers, but as will be shown later in this section, for
the structures investigated here the interpretation of the XRD
intensity profiles is more complex. Inspired by the observation
that the high-temperature phase of (4Bp-3,4Pr)12G1-CO2CH3
is a bilayer vesicular cubic structure, we decided to discriminate
between low-temperature hexagonal phases formed by hollow
and bilayer columns. The difficulty of distinguishing between
these two models arises from the complexity of assessing which
reconstructed electron density map corresponds to the physical
structure. A powder X-ray diffraction experiment yields the
integrated intensities of the diffraction peaks. These intensities
are proportional to the square of the structure factors. Thus, the
square root of the measured intensity, which after the appropriate
multiplicity correction we will refer to as the “amplitude”, allows
us to determine the relative magnitudes of the structure factors,
but not their phases. Lattice centrosymmetry reduces the
complexity of the “phase problem” for the investigated hex-
j
agonal, centered rectangular, and Pm3n cubic phases. In general,
phase values can range from 0 to π. However, for these
centrosymmetric lattices the phase values are restricted to being
either 0 or π.
Figure 5. Reconstructed relative electron density maps of the columnar
hexagonal phase self-organized from (4Bp-3,4)12G1-CO2CH3 (a), (4Bp-
3,4Pr)12G1-CO2CH3 (c, d), and (4Bp-3,4)12G1-CO2CH3 molecular models
based on the fitted parameters shown at scale with the corresponding electron
density maps (b). In all cases the diffraction peak phase + or - is indicated.
The parameters Daromatic, Dcore, and Daliphatic-in, extracted from the fits of the
experimental powder XRD data using the hhc models, provided the absolute
electron densities of the aromatic (Faromatic) and aliphatic (Faliphatic) regions
that were used to support the phase solutions proposed in (a) and (d) and
to eliminate the solution shown in (c).
Figure 5 illustrates the relative electron density distributions
of the columnar hexagonal phases self-organized from (4Bp-
3,4)12G1-CO2CH3 and (4Bp-3,4Pr)12G1-CO2CH3, recon-
structed from the intensities calculated from their powder X-ray
data shown in Figure 3g. From all the possible combinations
of phases, + or -, the solutions selected in Figure 5 followed
the general principle used to generate electron density maps
that exhibit a microsegregation of the aromatic and aliphatic
regions.7d,c,9 The significant relative intensity of the (11) and
(20) diffraction peaks, shown in Figure 3g, dominates the other
terms included in the reconstruction of the Fourier series of the
electron density maps. Therefore, independent of the amplitude
phase choice of the other higher order diffraction peaks, (21),
(30), (22), and (31), all the electron density maps exhibit a
polygonal-shaped aromatic distribution for the case of (10)+,
(11)-, and (20)-. Any other phase combination for these three
amplitudes did not generate the expected microsegregation of
the aromatic and aliphatic regions, and they were eliminated.
From the possible phase combination of the other diffraction
peaks, (21), (30), (22), and (31), for (4Bp-3,4)12G1-CO2CH3
one solution is shown in Figure 5a and for (4Bp-3,4Pr)12G1-
CO2CH3 there are two possible solutions shown in Figure 5c,d.
In addition, Figure 5 illustrates the excellent agreement of the
electron density distribution reconstructed from the experimental
amplitudes and from the hhc model fitted amplitudes, using the
analytical methodology that will be elaborated on in the next
subchapter.
singly segregated hollow polyhedral columns with the diameter
of the hollow region Dcore ) 14.8 ( 3.5 Å. Assuming that the
columns of the hexagonal phase assembled from (4Bp-
3,4Pr)12G1-CO2CH3 are also singly segregated, the molecular
model provided a lower bound of the diameter of the hollow
region of 27 Å (Supporting Information, Figure SF4). For the
hybrid (4Bp-3,4)12G1-CO2CH3 the hollow region corresponds
to a relatively small volume fraction that represents (Dcore
≈
14.8 Å/Dcol ) 69.1 Å)2 ≈ 4.5% of all the supramolecular
columns. On the other hand, for (4Bp-3,4Pr)12G1-CO2CH3 the
volume fraction of the hypothetical hollow region is more than
2 times larger (Dcore ≈ 27 Å/Dcol ) 84 Å)2 ≈ 10.3%. Assuming
that the addition of one or two methylenic units at the apex of
the dendron does not significantly strengthen dendron-dendron
interactions, it is unrealistic to observe such a large increase of
the hollow region since it would impart a significant free energy
penalty. To prove that the phase solution (+, -, -, -, -) shown
in Figure 5c does not correspond to a hollow singly segregated
column, we compare the diameter of the hollow center of 18
Å, provided by the simulation, with the 27 Å value calculated
from molecular model. The 27 Å value is 50% larger than the
18 Å fitted value, and therefore, the phase solution (+, -, -,
-, -) does not correspond to a hollow singly segregated
column. Therefore, we conclude that the columnar hexagonal
phase of (4Bp-3,4Pr)12G1-CO2CH3 is generated by supramo-
Molecular models of the columnar hexagonal phase and their
reconstructed electron density distribution shown in Figure 5a,b
demonstrate that (4Bp-3,4)12G1-CO2CH3 self-assembles into
(21) Percec, V.; Imam, M. R.; Bera, T. K.; Balagurusamy, V. S. K.; Peterca,
M.; Heiney, P. A. Angew. Chem., Int. Ed. 2005, 44, 4739–4745.
9
J. AM. CHEM. SOC. VOL. 132, NO. 32, 2010 11295

A R T I C L E S
Peterca et al.
Table 2. Calculation of the Number of Dendrons Forming the Inner Layer, µin, and Outer Layer, µout, of the Hybrid Dendritic Esters
Self-Assembled into Doubly Segregated Aliphatic-Aromatic Structures
a/2b (Å),
a/4c (Å)
f
g
R
(deg)
R′
(deg)
h
i
j
l
m
µout-B
compd
phasea
µd
λ, δe(Å)
µin-A
µout-A
µin-u
rk(Å)
µin-B
(4Bp-3,4Pr)12G1-CO2CH3
Φh
42.0
55.4
40.8
52.4
34.2
43.8
33.0
42.8
31.9
39.0
39.9
43.5
34.8
33.4
21
33
20
30
14
21
13
20
12
17
19
22
16
12
29, 14
29, 14
24.61
20.52
26.11
22.24
32.08
27.19
34.68
28.95
37.76
32.34
30.98
27.84
33.38
40.84
35.96
39.78
38.68
42.63
40.65
44.51
44.27
48.40
48.69
51.47
53.12
49.43
51.51
58.10
6.4
15.5
6.2
13.8
2.8
7.8
2.6
7.6
2.5
5.9
7.4
9.1
4.8
3.2
14.6
17.5
13.8
16.2
11.2
13.2
10.4
12.4
9.5
11.1
11.6
12.9
11.2
8.8
3.50
4.17
3.43
4.01
2.87
3.36
2.76
3.27
2.63
3.05
3.33
2.78
2.07
1.98
2.24
2.56
2.21
2.48
1.97
2.17
1.93
2.14
1.88
2.04
2.16
1.94
1.75
1.75
4.5
5.6
4.3
5.3
3.5
4.3
3.4
4.1
3.2
3.8
4.2
3.7
2.8
2.5
16.5
27.4
15.7
24.7
10.5
16.7
9.6
15.9
8.8
13.2
14.8
18.3
13.2
9.5
j
Pm3n
(4Bp-3,4Et)12G1-CO2CH3
(6 Np-3,4Pr)12G1-CO2CH3
(6 Np-3,4Et)12G1-CO2CH3
(4-3,4Pr)12G1-CO2CH3
Φh
27.8, 14
27.8, 14
27.2, 14
27.2, 14
26.1, 14
26.1, 14
25, 14
25, 14
23.8, 14
25, 11
j
Pm3n
n
Φh
j
Pm3n
n
Φh
j
Pm3n
n
Φh
j
Pm3n
j
(4-3,4Et)12G1-CO2CH3
(4Bp-3,4Et)dm8*G1-CO2CH3
(4Bp-3,4)Et6G1-CO2CH3
(6 Np-3,4)dm8*G1-CO2CH3
Pm3n
Pm3n
Pm3n
Φh
j
j
23, 9
24, 11
o
a
Lattice notation: Φh, columnar hexagonal; Φh , ordered columnar hexagonal; Pm3n, cubic. b Radius of the supramolecular assembly calculated for
the columnar hexagonal phases from a/2, where a is the lattice dimension listed in Table 1. c Radius of the supramolecular assembly calculated for the
cubic phases from a/4, where a is the lattice dimension listed in Table 1. d Number of dendrons per assembly cross-section as calculated in Table 1.
e The dendron length, λ, used in method A and average aliphatic region thickness, δ, used in method B were calculated from the molecular models with
mixed trans-gauche conformation for the alkyl chains shown in Figure SF4 (Supporting Information), assuming no assembly-to-assembly
o
j
f
interdigitation. Angles defined in Figure 6 were calculated using method A from eqs SE3 and SE4 (Supporting Information):R ) 2 sin-1[λ(a/2) sin(R′/
2)]. Angles defined in Figure 6 were calculated using method A from eqs SE3 and SE4 (Supporting Information): R′ ) π(a/2)2/(λ2µ/2). h Number of
g
dendrons forming the inner layer, calculated using method A from eq SE2 (Supporting Information): µin-A ) µ - µout-A.
i Number of dendrons forming
the outer layer, calculated using method A from eq SE2 (Supporting Information): µout-A ) 360°/R. j Number of dendrons (uncorrected, first iteration of
the nonlinear system of eqs SE5 and SE6 (Supporting Information)) forming the inner layer calculated using method B with r ) 0 in eq SE5: µin-u ) µ/
(a/δ). k Correction factor r calculated from r ) (3.5 Å/2)/sin[360°/(2 µin-u)] as shown in Figure 6b. l Number of dendrons forming the inner layer,
calculated using method B with nonzero correction factor r in eq SE5 (Supporting Information): µin-B ) µ/[1 + (aδ - δ2)/(δ - r)2]. m Number of
dendrons forming the outer layer, calculated using method B with nonzero correction factor r in eq SE5 (Supporting Information): µout-B ) µ - µin-B
.
n The bilayer assignment is not definitive; these hexagonal phases have relatively small Dcol
.
one additional structural parameter extracted from molecular
models, the length of the dendron, λ, for method A and the aliphatic
region thickness, δ, for method B. For the doubly segregated
supramolecular structures, the values presented in Table 2 indicated
that µin is always smaller than µout, as expected on the basis of the
mechanism illustrated in Scheme 3.
Therefore, the inner aliphatic region has a smaller total
number of electrons than the outer aliphatic region. At the same
time, the possibility that the inner confined aliphatic region can
be locally more compact than the outer aliphatic region cannot
be excluded. This in turn can generate a higher average electron
density at the core than at the periphery. Therefore, in general,
a bilayer structure can exhibit an electron density distribution
with a value at the core that is lower than, comparable to, or
higher than that at the periphery.
On the basis of this observation, the answer to the phase
problem, presented in Figure 5c,d, is extracted from the
systematic fits of the powder X-ray data obtained from models
that have a core region containing µin ) 0, 1, ..., 5, 6 dendrons
(Supporting Information, Tables ST4 and ST5). The fits for µin
e 3 converged to the phase solution (+, -, -, -, -) and
matched relatively well the experimental amplitudes, but
provided an unphysical small aromatic region. Therefore, the
electron density of the aromatic region, Faromatic, has larger than
expected values, ranging from 0.6 e- Å-3 for µin ) 0, to 0.55
e- Å-3 for µin ) 3. The fits for µin ) 5 and 6 converged to the
phase solution (+, -, -, +, +) matched better the experimental
amplitudes and provided physical parameters within the expected
range7c,22 of Faromatic ≈ 0.5 e- Å-3 and Faliphatic ≈ 0.3 e- Å-3
(Figure 5d, Tables ST4 and ST5). Combining all the above, we
conclude that the phase solution (+, -, -, +, +), shown in
Figure 5d, provides the electron density map consistent with a
bilayer hexagonal phase and that for this library of hybrid
Figure 6. Simplified models of the supramolecular assemblies forming
the hexagonal and cubic bilayer phases used to calculate the projection of
the solid angle of the dendron, R′, by method A (a) and of the close contact
correction factor, r, by method B (b). For clarity in (a) only one dendron
from the outer layer of the bilayer assembly is shown. a ) lattice parameter,
λ ) length of the dendron, R and R′ are the two indicated angles, δ )
aliphatic region thickness, and r ) close contact correction factor. Complete
details of the calculations are given in section 5.3 of the Supporting
Information.
lecular columns that are doubly segregated. At this point, it is
necessary to establish which of the two solutions shown in
Figure 5c,d, (+, -, -, -, -) and (+, -, -, +, +), corresponds
to a bilayer column.
2.3.2. Calculation of the Number of Dendrons Forming
the Inner and Outer Layers of Doubly Segregated Phases. Table
2 summarizes the values of the number of dendrons forming the
inner and outer layers of the bilayer assemblies, µin and µout,
respectively, calculated on the basis of the two new methodologies
illustrated in Figure 6 and detailed in subsection 5.3 of the
Supporting Information. Each of the two alternative methods uses
(22) Turner, D. C.; Gruner, S. M. Biochemistry 1992, 31, 1340–1355.
9
11296 J. AM. CHEM. SOC. VOL. 132, NO. 32, 2010

Self-Assembly of Hybrid Dendrons
A R T I C L E S
After integration, the scattering amplitude given by a hexagonal
distribution is
4F0
qxqy
a
2
a
2
√
Fhex(a, F0, qx, qy) )
2F0
sin qx sin 3 qy
+
(
)
(
)
a
a
2
√
cos(aqx) - cos qx - 3 qy
-
[
(
)
]
2
√
qy(qx + 3qy)
2F0
a
a
2
√
cos(aqx) - cos qx + 3 qy
(2)
[
(
)
]
2
√
qy(qx - 3qy)
Finally, the calculated scattering amplitude of the hhh model
shown in Figure 7, Fhhh, based on hexagonal distributions with
constant electron density for the aliphatic (Faliph), aromatic (Farom),
and core (Fcore) regions, is given by
F
hhh(qx, qy) ) Fhex(Raliph, Faliph, qx, qy) + Fhex(Rarom, Farom
aliph, qx, qy) + Fhex(Rcore, Fcore - Farom, qx, qy) (3)
-
F
The scattering amplitude, Fhhc, of the alternative hhc model
shown in Figure 7, consisting of aliphatic and aromatic regions
with hexagonal constant electron density distributions and a
cylindrical core of constant electron density, is given by eq 4,
with Fcyl given by eq 5, deduced previously.9f
Figure 7. Geometric representation of the hexagonal distribution F(x,y) and
schematic of the models used in the powder XRD simulations. The equations
defining the dashed boundary of the shaded domain are indicated.
F
hhc(qx, qy) ) Fhex(Raliph, Faliph, qx, qy) + Fhex(Rarom, Farom
-
F
aliph, qx, qy) + Fcyl(Rcore, Fcore - Farom, qx, qy) (4)
dendrons the threshold between singly and doubly segregated
columns is somewhere between 4.5% and 10.3% empty volume
fraction. Therefore, none of the other investigated structures
functionalized with C12H25 or dm8* alkyl chains (Schemes 1,
2) are expected to form hollow columns if their hypothetical
empty volume fraction is larger than 10.3% because the strength
of their aromatic interactions is either comparable or smaller
and consequently cannot stabilize such a large hollow cavity.
2.3.3. Simulation of the Powder X-ray Diffraction Data of
Hollow, Nonhollow, and Singly and Doubly Segregated
Polyhedral Columns Self-Organized into Hexagonal Phases. The
reconstructed electron density maps shown in Figure 5 dem-
onstrate that the increase of the relative intensity of the higher
order diffraction peaks is generated in part by the electron
density variation within the supramolecular columns. This
variation is from the higher value of the aromatic region to the
lower one of the hollow center for singly segregated columns
(Figure 5a) or of the inner aliphatic region for doubly segregated
columns (Figure 5d). Furthermore, the shape of the high electron
density region is very close to an ideal hexagon. Therefore,
simulations of the X-ray powder diffractograms of the hexagonal
phases with unusual amplification were calculated from the
general equation of the scattering amplitude applied to the
models shown in Figure 7:
J
(q R)2 + (q R)2
x y
√
1
Fcyl(R, F, qx, qy) ) 2πR2F
(5)
(q R)2 + (q R)2
√
x
y
The simulated X-ray powder diffraction amplitudes used in
Figure 5 are presented in Figure 8 for the case of singly
segregated polyhedral columns and in Table ST5 (Supporting
Information) for the case of doubly segregated polyhedral
columns. These simulations are based on eqs 3 and 4, following
the procedure detailed in section 5.2 of the Supporting Informa-
tion. The agreement between the experimental and fitted
amplitudes is shown in Figure 8a for (6Np-3,4)12G1-CO2CH3
and in Figure 8b for (4Bp-3,4)12G1-CO2CH3for the hhh and
hhc models. The amplitudes given by these two models fitted
the experimental ones within the calculation error of 10-20%.
Furthermore, Figure 5a illustrates the agreement of the electron
density maps reconstructed from the experimental and hhc
model fitted amplitudes for (4Bp-3,4)12G1-CO2CH3 and their
agreement with the molecular model built on the basis of the
fitted 14.8 ( 3.5 Å hollow region diameter. The small difference
observed between the amplitudes fitted by the model with a
circular (hhc model in Figure 7) versus polygonal (hhh model
in Figure 7) core region is expected, considering the relatively
limited number of Fourier components included in the analysis.
On the other hand, the fitted amplitudes based on the hcc model
with circular-shaped aromatic and core regions, exhibited a
significantly larger deviation of the (21) diffraction peak
amplitude, (hcc model fitted amplitudes indicated in Figure 8
by the green-colored tilted squares). Therefore, the simulations
of the powder XRD data from Figures 5 and 8 demonstrated
that the unusual amplification of the higher order diffraction
peaks is correlated both with the presence of a low electron
density region at the center of the columns and with the
polygonal shape of the aromatic region. These two effects cannot
F(bq) )
F(br) eibqbr dbr
(1)
∫
Using the hexagonal distribution F(x,y) defined in Figure 7,
the appropriate integration limits of eq 1 are
Fhex(a, qx, qy)
)
-a/2 dx
3(a+x) dy cos(qxx + qyy) +
√
-
√
3(a+x)
∫
∫
-a
F0
a/2
√
a
3/2
dx -a 3/2 dy cos(qxx + qyy) +
∫
∫
√
-a/2
a
√
3(a-x)
dx
3(a-x) dy cos(qxx + qyy)
∫ ∫√
a/2
-
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J. AM. CHEM. SOC. VOL. 132, NO. 32, 2010 11297

A R T I C L E S
Peterca et al.
Figure 8. SAXS powder data collected in the columnar hexagonal phase from (6Np-3,4)12G1-CO2CH3 (a) and (4Bp-3,4)12G1-CO2CH3 (b). Diffraction
peak indexing and multiplicity, together with experimental (red squares) and fitted (red circles, red triangles, and green tilted squares) scaled amplitudes, are
indicated. The two lower right insets depict the electron density maps, reconstructed from the experimental amplitudes, and their surface representation.
the Φho phase. The possible tilt conformation shown in Figure
9d is also suggested by the comparison of the lattice dimension
of a ) 43.1 Å for the (4-3,4Et)12G1-CO2CH3 dendron with a
) 52.3 Å for the corresponding (4-3,4Et)12G1-CH2OH dendron.
In addition, the relative intensities of the higher order X-ray
powder diffraction peaks of (4-3,4Et)12G1-CO2CH3, shown in
Figure 1a, are at the highest levels observed thus far for any
self-assembling benzyl ether dendron. The relative electron
density maps (reconstructed from the experimental and from
the hhh model fitted amplitudes via eq 3 with Rcore ) 0) shown
in Figure 9c demonstrated that the (4-3,4Et)12G1-CO2CH3
dendron self-assembles into nonhollow polyhedral columns,
presented in Figure 9d.
2.3.5. From Hollow Polyhedral Columns to Nonhollow
Bilayer Polyhedral Columns via Changes of the Dendron
Alkyl Periphery. The results discussed thus far revealed a
complex correlation among the dendritic aromatic region, the
apex building block, and the self-assembly process. Bilayer
hexagonal and cubic phases were observed for all the dendrons
with 3,4Et and 3,4Pr groups at the apex (Table 2) but not in
the closely related (4Bp-3,4)12G1-CO2CH2CH2OCH3. The
results presented in Figure 10 further expand this complexity:
upon the functionalization of the (6Np-3,4)-R-G1-CO2CH3
dendron periphery with chiral chains (Schemes 1 and 2, R )
dm8*), it was observed that the self-assembly preserved the
pathway of forming a columnar hexagonal phase, but that the
lattice dimension increased by 5 Å. This is unexpected consider-
ing that the length of the dendron was reduced (Figure 10a).
Figure 10b compares the relative electron density distribution
of the hollow singly segregated polyhedral columns of (6Np-
3,4)12G1-CO2CH3 with the two possible solutions for (6Np-
3,4)dm8*G1-CO2CH3. If the self-assembly process is not
influenced by the change of the periphery, path II in Figure
10b, the diameters of the column and of the empty core region
should decrease. On the other hand, if the self-assembly pathway
is changed from singly to doubly segregated columns by the
addition of the chiral centers, the diameters of the column and
of the lower electron density core region should increase (path
I in Figure 10b). Clearly, only the latter case is supported by
the experimental data. Interestingly, wide angle oriented fiber
X-ray diffraction data (Figure SF5, Supporting Information)
demonstrated that the unusual formation of a bilayer columnar
Figure 9. WAXS patterns collected from the oriented fibers of (4-3,4)12G1-
CO2CH3 (a) and (4-3,4Et)12G1-CO2CH3 (b). Relative electron density maps
reconstructed from the experimental and fitted amplitudes (c) and molecular
o
model (d) of (4-3,4Et)12G1-CO2CH3 in the Φh phase.
be separated. Hence, the parameters were fitted with larger error
intervals of approximately (3.5 Å.
2.3.4. Singly Segregated Nonhollow Polyhedral Columns.
One of the most surprising results observed in the self-assembly
of the first-generation benzyl dendritic esters is the unusual
decrease of the lattice dimension of the columnar hexagonal
phase upon the change of the apex group from 3,4 to 3,4Et.
The analysis of the WAXS fiber patterns, shown in Figure 9a,b
for the two structures, demonstrated that the unusual decrease
of the lattice dimension of ∆a ) -14 Å is accompanied by the
formation of long-range intercolumnar order and by a possible
tilt-conformation1q of the (4-3,4Et)12G1-CO2CH3 dendron in
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11298 J. AM. CHEM. SOC. VOL. 132, NO. 32, 2010

Self-Assembly of Hybrid Dendrons
A R T I C L E S
aromatic layer to the lower value of the inner aliphatic layer or
of the empty core. At this point, it is necessary to elucidate
why the aromatic region of all the structures that self-assembled
into bilayer columns adopt a polyhedral shape.
2.4. Analysis of the Cubic Phases Self-Organized from
Polyhedral Vesicles. The formation of bilayer vesicular phases
is triggered by the addition of one or two methylenic units to
the apex of the dendron (Table 1). The 3-dimensional recon-
structed electron density distributions are shown in Figure 11b
for the smallest, (4-3,4Pr)12G1-CO2CH3, and largest, (4Bp-
3,4Pr)12G1-CO2CH3, first-generation dendrons investigated. The
similarity of the high electron density regions to the Voronoi
j
polyhedral representation of the Pm3n unit cell is remarkable.
It is most probable that the mechanism that triggers the
formation of polyhedral columns is also responsible for generat-
ing the polyhedral vesicles.
The at-scale comparison of the electron density maps of the
plane z ) 0 and of their corresponding profiles shown in Figure
11c,d illustrates the gradual increase of the size of the supramo-
lecular clusters and the gradual decrease of the relative electron
density at their centers. This gradual process follows the
reduction of the solid angle of the dendron, generated by the
increase of the length of the aromatic region. It is remarkable
to what extent these small additions impact the change of the
cluster size: an estimated 4 Å increase of the length of the unit
(Figure 2, 36.7 Å [L for (4Bp-3,4Pr)12G1-CO2CH3] - 32.7 Å
[L for (4-3,4Pr)12G1-CO2CH3] ) 4 Å) translates into an 8-fold
shift of the cluster size (Table 1, (221.5 - 155.9)/2 ) 32.8 Å).
2.4.1. Simulation of the X-ray Powder Diffraction Data of
Polyhedral Doubly Segregated Vesicles. The simulations of the
X-ray powder diffraction data were performed via a new
methodology (Figure 12), which was inspired by the similarity
of the estimated shape of the aromatic region of the vesicles to
the corresponding Voronoi polyhedral representation of the
Figure 10. Fully extended molecular models of the naphthyl methyl ether
hybrid dendrons functionalized with achiral (left) and chiral (right) alkyl
chains in an all-trans conformation (a). Corresponding reconstructed relative
electron density distributions presented at scale (b) and the corresponding
molecular models of the hollow singly segregated and nonhollow doubly
segregated polyhedral columns (c).
j
Pm3n lattice (Figure 11b). Using eq 1, the X-ray powder
hexagonal phase upon the addition of the chiral centers is
accompanied by the formation of additional long-range intra-
and intercolumnar correlations. The additional features observed
in the XRD fiber pattern of the chiral dendron can be correlated
with a possible dendron tilt conformation1q and also with the
formation of a supramolecular dimer. Therefore, although the
solid angle of the dendron was expected to decrease upon
the change from achiral to chiral chains, the formation of additional
long-range correlations suggests that the chiral dendron might have
a different conformation. Because the assignment of these additional
features observed in the fiber XRD patterns is not definitive, the
exact changes of the 3-dimensional conformations of the dendrons,
mediated by the addition of chiral centers, are not known. In the
next section a second example of a bilayer phase induced via alkyl
branching will be described.
These results, in combination with the data shown in Figures
1, 5, 9, and 10, illustrate a variety of polyhedral self-assembled
structures with a comparable increase of the relative intensity
of the higher order X-ray diffraction peaks. Analysis of the
library of dendrons shown in Scheme 2 revealed the complexity
of the process required to reconstruct the electron density maps
and to assign the self-assembled structure as hollow or non-
hollow and singly segregated or doubly segregated polyhedral
supramolecular columns. Simulations of the XRD data combined
with molecular models demonstrated that the significant en-
hancement of the higher order diffraction peaks of the hollow,
nonhollow, or bilayer columnar hexagonal phases was generated
by the polyhedral shape of the aromatic region and by the
variation of the electron density from the higher value of the
diffraction scattering amplitudes for this phase are given by
8
F(bq) ) A
[F (bq, Faliph, Raliph) +
j
∑
j)1
Fj(bq, Farom - Faliph, Rarom) + Fj(bq, Fcore - Farom, Rcore)] (6)
In eq 6 A is the scaling factor, and the eight functions Fj are
given by
F (bq, F, ꢀ) ) F δ (br, ꢀ) eibq·br dbr
(7)
∫
j
j
The calculation of eq 7 was performed by multidimensional
numerical integration after introduction of the function δj. This
function was deduced from the scaled Voronoi tessellation
f
shown in Figure 12, and it is defined in eq 8, with ꢀi given by
eq 9.
f
1, |br - brj| e |br - ꢀi(bri, brj, ꢀ)|, ∀ꢀi ∈ Λ, i * j
δj(br, ꢀ) )
f
{
0, |br - brj| > |br - ꢀi(bri, brj, ꢀ)|, ∀ꢀi ∈ Λ, i * j
(8)
f
ꢀi(bri, brj, ꢀ) ) ꢀ · bri + (1 - ꢀ)brj
(9)
In eqs 8 and 9, Λ ) {(-0.5, -0.5, -0.5), ..., (0.25, 0, 0.5), ...,
j
(1.5, 1.5, 1.5)} is a set of the Pm3n lattice points that covers
the range {-0.5 e x e +1.5, -0.5 e y e +1.5, -0.5 e z e
+1.5, } and brj are the vectors to the center of the eight
9
J. AM. CHEM. SOC. VOL. 132, NO. 32, 2010 11299

A R T I C L E S
Peterca et al.
Figure 11. SAXS powder diffraction data collected from (4-3,4Pr)12G1-CO2CH3 in the cubic phase (a). Reconstructed relative electron density distributions
shown only for the high density regions (b). Reconstructed relative electron density maps of the plane z ) 0.5 shown at scale (c). Relative electron density
profiles of the z ) 0.5 plane along the x direction marked in panel c (d). In panel a, diffraction peak indexing and phases (+ or -) used in the electron
density reconstructions are indicated, and the dashed rectangle indicates the region with overlapped diffraction peaks.
j
Figure 12. Geometric representation of the scaled Voronoi tessellation of the Pm3n cubic lattice. In (a) the unit cell is shown in normalized coordinates.
In (b) the 3-dimensional representation of the scaled Voronoi tessellation is shown for ꢀ ) 0.7 (for clarity only one center and one face polyhedron are
shown). In (c) the spatial linear transformation used to calculate the scaled tessellation is shown for the lattice point Pj ) (0.25, 0, 0.5).
j
polyhedrons that form the basis of the Pm3n cubic lattice defined
parameter ꢀ, as illustrated in Figure 12. For example, the special
case of ꢀ ) 1.0 corresponds to the case when all the polyhedrons
completely fill the unit cell, as illustrated by the Voronoi
representation shown in Figure 11b.
as {brj} ) {(0, 0, 0), (0.5, 0.5, 0.5), (0.5, 0.25, 0), (0.5, 0.75, 0),
(0.25, 0, 0.5), (0.75, 0, 0.5), (0, 0.5, 0.25), (0, 0.5, 0.75)}. For
all the fits, the scale of the Voronoi tessellation is given by the
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11300 J. AM. CHEM. SOC. VOL. 132, NO. 32, 2010

Self-Assembly of Hybrid Dendrons
A R T I C L E S
Simulations based on the scaled Voronoi tessellation meth-
odology and eq 6, shown in Figure 11, demonstrated that the
enhanced amplitudes are generated by a combination of the
polyhedral shape of the clusters and by the variation of
the electron density from the higher value of the aromatic region
to the lower value of the inner aliphatic region. Furthermore,
the intensity profiles of the biphenyl methyl ether hybrid
dendrons with 3,4Et and 3,4Pr groups at the apex were
consistent only with fits to a model that has an additional hollow
center. It is most probable that the additional degree of freedom
of the biphenyl aryl-aryl sp2-sp2 bond triggered a slightly
different self-assembly mechanism. The corresponding benzyl
ether and naphthyl methyl ether dendrons lack this additional
conformational freedom. A relatively small torsion around the
biphenyl aryl-aryl sp2-sp2 bond can significantly reduce the
solid angle of the dendritic unit. This process can account for
the observed increase of the lattice dimensions and of the higher
order diffraction peaks’ relative amplitudes for both columnar
and cubic phases upon the change from naphthyl methyl ether
to biphenyl methyl ether dendrons (Figure 1).
The agreement between the experimental and Voronoi scaled
fitted amplitudes is illustrated in Figure 11 by the reconstructed
relative electron density distributions. Figure 11b compares the
experimental and simulated high electron density 3-dimensional
distributions of the (4-3,4Pr)12G1-CO2CH3, with the complete
distributions detailed in Figure 11c for the plane z ) 0.5. The
fitted parameters ꢀ are also indicated for the smallest and largest
structures: (4-3,4Pr)12G1-CO2CH3 and (4Bp-3,4Pr)12G1-
CO2CH3. In both cases, the fitted parameters provided a good
estimate for the thickness of the outer aliphatic layer: (1 -
ꢀ
aromatic) × 155.9 Å/4 ) 12.7 Å and (1 - ꢀaromatic) × 221.5 Å/4
) 13.9 Å, respectively. These two values were calculated in
the direction parallel to the close contact of the assemblies from
the face of the Pm3n lattice.
j
The assessment of a relatively small hollow center with a
diameter of ∼20 Å was based on the reconstructed electron
density distributions shown in Figure 11d and on the Voronoi
fits presented in Supporting Information Figure SF10. This small
hollow center translates to an empty volume fraction of less
than 1% from the supramolecular structure: 8(4π/3)(20 Å/2)3/
(221.5 Å)3 ) 0.31%. In addition, the molecular modeling shown
Figure 13. Reconstructed relative electron density maps shown at scale
(a), corresponding small-angle X-ray powder diffraction data collected upon
cooling from the isotropic phase (b), and wide- and small-angle X-ray
diffraction patterns collected in the Φr-c phase from the oriented fiber of
(4Bp-3,4)Et6G1-CO2CH3 (c).
o
(6Np-3,4Pr)12G1-CO2CH3 to (4Bp-3,4Pr)12G1-CO2CH3 the
expected lattice dimension is 175.3 Å + 8(36.7 - 34.9) Å )
175.3 + 14.4 Å ) 189.7 Å. This value is 31.8 Å smaller than
j
in Figure 2 in combination with the Pm3n lattice parameters of
the three structures presented in Figure 11c,d also supports the
idea that the sharpest dendron, (4Bp-3,4Pr)12G1-CO2CH3, self-
assembles into a hollow vesicle, as follows. Assuming that the
change of the aromatic region structure does not significantly
change the density of the aliphatic region and that the vesicles
self-assembled from (4-3,4Pr)12G1-CO2CH3 have a very small
j
the experimental value of a(Pm3n) ) 221.5 Å. Therefore, this
significant difference suggests that the vesicles self-assembled
from (4Bp-3,4Pr)12G1-CO2CH3 are hollow.
2.5. Principles of Formation of Polyhedral Singly and
Doubly Segregated Columns and Vesicles. The self-assembly
process of the hybrid biphenyl methyl ether dendron function-
alized with a second type of branched alkyl periphery, (4Bp-
3,4)Et6G1-CO2CH3, is summarized in Figure 13. This is the
only dendritic architecture containing a 3,4 group at the apex
that exhibits a bilayer cubic phase. Interestingly, no cubic phase
was observed upon the self-assembly of this dendron function-
alized with dm8* chiral chains.23 The biphenyl methyl ether
hybrid (4Bp-3,4)Et6G1-CO2CH3 dendron self-assembles at low
temperatures into a centered rectangular phase with a unique
characteristic. This is the only centered rectangular phase with
an angle between the a and b directions of the lattice smaller
j
hollow center, we can extrapolate the Pm3n cubic lattice
dimension from the length of the dendritic units shown in Figure
2. Upon the change from (4-3,4Pr)12G1-CO2CH3 to (6Np-
3,4Pr)12G1-CO2CH3 the lattice dimension is expected to be
155.9 Å[(4-3,4Pr)12G1-CO2CH3] + 8(34.9 - 32.7) Å ) 155.9
+ 17.6 Å ) 173.5 Å. The multiplication factor 8 accounts for
the fact that two bilayer assemblies span through one side of
j
the Pm3n unit cell and that four dendrons span through one
bilayer assembly. The calculated values are slightly overesti-
mated because they are not corrected for interdigitation. The
j
experimental value of a(Pm3n) ) 175.3 Å is almost 2 Å larger
than the expected value. This small difference suggests that the
vesicle self-assembled from (6Np-3,4Pr)12G1-CO2CH3 has a
hollow region only if those self-assembled from (4-3,4Pr)12G1-
CO2CH3 are hollow. On the other hand, upon the change from
(23) Kim, A. J.; Kaucher, M. S.; Davis, K. P.; Peterca, M.; Imam., M. R.;
Christian, N. A.; Levine, D. H.; Bates, F. S.; Percec, V.; Hammer,
D. A. AdV. Funct. Mater. 2009, 19, 2930–2936.
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A R T I C L E S
Peterca et al.
Figure 14. Reconstructed relative electron density maps shown at scale (a) and molecular models of the column and vesicle cross-section (b). Small-angle
X-ray diffraction patterns collected from the oriented fiber of (4Bp-3,4Pr)12G1-CO2CH3 indicating the reversible epitaxy among lamellar, centered rectangular,
and hexagonal phases and the irreversible epitaxy upon the transition from hexagonal to cubic (c). Schematic of the (001)hexagonal-(111)cubic epitaxy (d).
than the special value of 60° (Table 1; Supporting Information,
Table ST2). The γ angle was measured in the triangle formed
by the centers of three first-order neighboring columns, Figure
13a. This latter value is achieved in the case of 2b ) a cos 60°,
when the centered rectangular lattice reduces to the particular
case of the hexagonal lattice (Figure 13a). In general, centered
rectangular phases are expected to exhibit an angle γ larger than
60° because the close contact direction of the supramolecular
columns is expected to be perpendicular to their long-axis
direction, as shown, for example, in the electron density map
from Figure 14a. These two observations suggest a complex
correlation of the dendron periphery and the formation of
polyhedral and bilayer phases for the case of the (4Bp-
3,4)Et6G1-CO2CH3 hybrid dendrons.
A closer inspection of the lattice parameters and of the relative
electron density maps reconstructed for the (4Bp-3,4Pr)12G1-
CO2CH3 dendron presented in Figure 14 revealed the thermally
induced changes in the structure that trigger a complex phase
diagram. At low temperatures the dendron self-assembles into
a bilayer lamellar ordered phase, with a double layer thickness
d001 ) 63.2 Å. With an increase of the temperature above 90
°C (Figure 4), the rotational energy barriers of some of the bonds
are comparable with the thermal energy and the dendrons tend
to pack their aromatic regions closer together by forming
asymmetric columns, while preserving the thickness of the
lamellar phase bilayer (bcentered rectangular ) 62.4 Å is comparable
with d001 ) 63.2 Å of the low-temperatures lamellar phase).
Upon increasing the temperature above 119 °C, the structures
minimize further their aromatic free energy by forming the more
symmetric bilayer columns of the hexagonal phase, while
preserving upon this transition the longer column dia-
meter of their low-temperature centered rectangular phase
(acentered rectangular/2 ) 170.8/2 ) 85.4 Å is comparable with
ahexagonal ) 84.0 Å). The process described thus far involves
in-plane small translations and rotations of the dendrons. This
mechanism was confirmed by the reversible epitaxial correla-
tions presented in Figure 14c,d. The most complex process
occurs when the temperature exceeds 139 °C during the
formation of the dendritic vesicles. At this temperature, the
thermal energy is at the level that the structure departs from
the 2-dimensional taperlike conformation, forming a 3-dimen-
sional conelike conformation, with the conformation of the alkyl
chains predominantly controlling this process.
While the reversible epitaxial correlations illustrated in Figure
14c,d are not unusual, the irreversible (001)hexagonal-to-(111)cubic
epitaxy is remarkable. Although its direction is explained in
Figure 14d by the preservation of the supramolecular packing
rotational symmetry, such an effect was seen only in a few
dendritic structures.1t The WAXS diffraction data, collected in
the hexagonal and cubic bilayer phases, exhibit diffuse meridi-
onal features positioned at the average alkyl chain-chain
correlation distance that indicate that the alkyl chains have a
liquidlike conformational freedom. Therefore, the hexagonal-
to-cubic epitaxy can be explained only by cluster-to-cluster
interactions and by the conservation of some of the hexagonal
phase polyhedral faces. In other words, the thermally induced
supramolecular shape change follows the path of minimum
required energy provided by the minimum rotation and transla-
tion of the units.
Figure 15 summarizes the combined analysis of the self-
assembly and self-organization process of the amphiphilic
dendrons that is updated with the bilayer polyhedral structures
discovered in this study. In general, the equilibrium configuration
of any self-assembled system is achieved when the free energy
is at the minimum. In most self-assembled supramolecular
dendrimers, the equilibrium configuration corresponds to the
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Self-Assembly of Hybrid Dendrons
A R T I C L E S
Figure 15. Definition of the mean cm and Gaussian cg curvatures for a cylinder (a) and a sphere (b), where Rmin and Rmax are, respectively, the minimum
and maximum possible values of the radii of the curve obtained by intersecting an arbitrary plane and the corresponding object. Mechanism of self-assembly
into singly and doubly segregated assemblies (c) and of their self-organization into polyhedral-shaped supramolecular columns and vesicles (d). In (c) the
schematic follows from left to right the increase of cm, cg, and temperature, separated for the case of the tapered dendron (left, cg ) 0) and the conical
dendron (right, cg > 0). The two curvatures of the surface of the supramolecular assemblies, cm and cg, are represented by the dotted lines colored in pink
and green, respectively, illustrating that a “sharp” dendron self-assembles into a cluster with small curvature (or alternatively large radii) and a “wide”
dendron self-assembles into a cluster with large curvature (or alternatively smaller radii).
close-packing configuration illustrated in Figure 15c. This is
valid in the conditions when the dominant intramolecular and
intermolecular short-range dipolar interactions achieve their
maxima by close-packing groups of covalently bonded atoms
of similar species and spatial configurations. In this respect, the
phase diagram shown in Figure 15c does not take into account
a number of specific interactions, such as ionic or H-bonding,
that can inhibit the formation of bilayer columns and spheres.
At the same time, the formation of close-packing configurations
can be viewed as following the minimization of the outer surface
free energy of the assemblies, demonstrated previously.24
Therefore, in Figure 15a,b two special surfaces are shown,
cylindrical and spherical, to illustrate the definition of the mean
(cm) and Gaussian (cg) curvatures. The dendritic building block
is schematically represented by a taper, when cg ) 0, and by a
cone, when cg > 0. In Figure 15c, from left to right, the
temperature, mean curvature, and Gaussian curvature, separated
for systems with zero and nonzero Gaussian curvatures, cg,
increase.
The dependence from Figure 15 corresponds to both thermal
architectural changes, because the increase of cm and of cg can
be generated by an increase of temperature or by direct changes
of the primary structure of the dendron. With the exception of
the predicted hollow bilayer columnar structures, all the other
structures were observed in the proposed order, in the library
of hybrid dendrons investigated here or in other dendritic
libraries.7c,9 For clarity, Figure 15c illustrates the self-assembly
process for the case when the cluster-to-cluster correlations are
negligible. For example, this corresponds to self-assembly in
dilute solutions. Figure 15d illustrates the result of the self-
assembly and self-organization process when the supramolecular
cluster-to-cluster correlations are not neglected. Upon “cluster-
ing”, the network of short-range van der Waals attractive
interactions between the periphery of the assemblies generates
planar boundaries with their first-order neighboring clusters.
A variety of classes of structures forming faceted vesicles8,25,26
and polygonal sheets27 have been reported previously. In
comparison with the dendritic polyhedral-shaped structures
presented here, their formation was sometimes attributed to a
possible crystallization of the surfactant film25a and to
quenching.25b Interestingly, in at least two cases26 polygonal
structures have been observed to spontaneously form in closely
packed clusters. These two examples are in agreement with our
(24) (a) Ziherl, P.; Kamien, R. D. Phys. ReV. Lett. 2000, 85, 3528–3531.
(b) Ziherl, P.; Kamien, R. D. J. Phys. Chem. B 2001, 105, 10147–
10158. (c) Bates, F. S.; Fredrickson, G. H. Annu. ReV. Phys. Chem.
1990, 41, 525–527. (d) Matsen, M. W.; Bates, F. S. Macromolecules
1996, 29, 10914–1098. (e) Matsen, M. W.; Bates, F. S. J. Chem. Phys.
1997, 106, 2436–2448.
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A R T I C L E S
Peterca et al.
Scheme 4. Correlation between the Structure of the Dendrons and the Shape of Their Supramolecular Assemblies
hypothesis that the supramolecular cluster-to-cluster interactions
are the dominant factor in templating the polyhedral-shaped
dendritic structures.
and columnar phases presented here. All the doubly segre-
gated structures have as an intrinsic characteristically large
µ, due to the fact that their formation requires small cm and
cg.
The supramolecular dendrimers tend to adopt shapes closer
and closer to that of the idealized polyhedra templated by
their self-organization, but this process depends on the
number of dendrons, µ, forming the assemblies. In general,
a relatively large µ is required to observe supramolecular
assemblies with well-defined close-to-planar boundaries
(Scheme 4). For example, recent work elucidated the forma-
tion of spherical and oblate spherical supramolecular as-
semblies from a library of dendrons containing a carboxylic
acid at their apex.1s Because for this library the number of
dendrons forming the supramolecular assemblies was smaller
than 12, the two shapes reported previously can be considered
just rough approximations of the two types of Voronoi
3. Conclusions
The synthesis and structural analysis of three libraries of
first-generation hybrid self-assembling dendrons revealed
unprecedented supramolecular structures and pathways to
self-assembly and self-organization. Dendrons that self-
assemble into hollow and nonhollow polyhedral-shaped singly
and doubly segregated aliphatic-aromatic supramolecular
columns and vesicles were discovered. The mechanism of
assembly of these new bilayer structures was shown to follow
similar pathways that lead to the formation of cellular
membranes. In the case of the dendritic bilayer columns and
vesicles, the hydrophobic-hydrophilic interaction, which
mediates the formation of cellular membranes, was replaced
by a complex network of supramolecular interactions that
templates an outer layer with small curvature determined by
the solid angle of the dendron and an inner layer that
interdigitates with the outer layer. The significant difference
between the polygonal shape of the bulk dendritic bilayer
supramolecular structures and that of the biological vesicles
assembled in water is determined by the supramolecular
cluster-to-cluster correlations. These correlations dominate
the self-organization process of the doubly segregated
supramolecular dendrimers. In the water phase of the cellular
membranes the cluster-to-cluster correlations are negligible,
and therefore most of them are globular rather than polyhe-
dral. In addition, this study provided experimental data
needed to elaborate a detailed mechanism of the self-assembly
and of self-organization of supramolecular dendrimers into
singly and doubly segregated phases. This mechanism
predicts new supramolecular organizations and explains
unusual changes of the internal packing of the supramolecular
structures observed at high temperature, from singly segre-
gated columns to doubly segregated vesicles and from doubly
j
polyhedra present in the Pm3n lattice. Whereas in the case
of the columnar and cubic bilayer phases reported in Table
1, the number of dendrons forming the doubly segregated
supramolecular structures is always sufficiently large such
that the assemblies adopt shapes that are much closer to the
that of the idealized polyhedra templated by their self-
organization, as illustrated in Scheme 4. Furthermore, in the
case of the singly segregated phases reported in Table 1,
polyhedral-shaped structures were observed only for hollow
structures, which are also assembled from a larger number
of dendrons,7c,9 and in the two special cases discussed, (4-
3,4Et)12G1-CO2CH3 and (4Bp-3,4)Et6G1-CO2CH3. There-
fore, the mechanism proposed in Figure 15 elucidates why
polyhedral structures are omnipresent in the bilayer cubic
(25) (a) Antunes, F. E.; Marques, E. F.; Gomes, R.; Thuresson, K.; Lindman,
B.; Miguel, M. G. Langmuir 2004, 20, 4647–4656. (b) Raspaud, E.;
Pitard, B.; Durand, D.; Aguerre-Chariol, O.; Pelta, J.; Byk, G.;
Scherman, D.; Livolant, F. J. Phys. Chem. B 2001, 105, 5291–5297.
(26) (a) Borne, J.; Nylander, T.; Khan, A. J. Phys. Chem. B 2002, 106,
10492–10500. (b) Jung, H. T.; Coldren, B.; Zasadzinski, J. A.;
Iampietro, D. J.; Kaler, E. W. Proc. Natl. Acad. Sci. U.S.A. 2001, 98,
1353–1357.
(27) Li, Z. B.; Hillmyer, M. A.; Lodge, T. P. Nano Lett. 2006, 6, 1245–
1249.
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Self-Assembly of Hybrid Dendrons
A R T I C L E S
P. Roy Vagelos Chair at the University of Pennsylvania is gratefully
acknowledged.
segregated columns to doubly segregated hollow vesicles.
The principles of the self-assembly process into doubly
segregated structures provide access to the design of complex
supramolecular organizations that can be used for applications
such as molecular containers and polyhedral nanoparticles
and for mimicking in bulk complex biological tubes and
vesicles.
Supporting Information Available: Experimental procedures
with complete spectral, structural, and retrostructural analysis
and complete ref 8. This material is available free of charge
via the Internet at http://pubs.acs.org.
Acknowledgment. Financial support by the National Science
Foundation (Grants DMR-0548559 and DMR-0520020) and the
JA104432D
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