Rational design of the first spherical supramolecular dendrimers self-organized in a novel thermotropic cubic liquid-crystalline phase and the determination of their shape by X-ray analysis

Article abstract of DOI:10.1021/ja963295i

The rational design, the synthesis via a new convergent approach, and the characterization of four generations of monodendrons based on the AB₃ building block methyl 3,4,5-trishydroxybenzoate are described. The first generation monodendrons are

Full text of DOI:10.1021/ja963295i

J. Am. Chem. Soc. 1997, 119, 1539-1555
1539
Rational Design of the First Spherical Supramolecular
Dendrimers Self-Organized in a Novel Thermotropic Cubic
Liquid-Crystalline Phase and the Determination of Their Shape
by X-ray Analysis
V. S. K. Balagurusamy,† G. Ungar,† V. Percec,*,‡ and G. Johansson‡
Contribution from the Department of Engineering Materials and Centre for Molecular Materials,
The UniVersity of Sheffield, Sheffield S1 3JD, UK, and The W. M. Keck Laboratories for Organic
Synthesis, Department of Macromolecular Science, Case Western ReserVe UniVersity,
CleVeland, Ohio 44106-7202
ReceiVed September 19, 1996X
Abstract: The rational design, the synthesis Via a new convergent approach, and the characterization of four generations
of monodendrons based on the AB3 building block methyl 3,4,5-trishydroxybenzoate are described. The first generation
monodendrons are crystalline. The second generation methyl 3,4,5-tris-3′,4′,5′-[tris(n-dodecyloxy)benzyloxy]benzoate
(12Gn-AG-CH3, n ) 2), the corresponding benzyl alcohol (12G2-AG-CH2OH) and benzoic acid (12G2-AG), and
all higher generation monodendrons with n ) 3 and 4 exhibit in addition to the crystal phase an isomorphous cubic
liquid-crystalline (LC) phase of Pm3hn space group. The cubic unit cell parameters of 12G2-AG, 12G3-AG, and
12G4-AG are 68.3, 79.2, and 84.0 Å, respectively. Computed electron density profiles demonstrated that in the
cubic phase 12, 6, and 2 monodendrons of generation 2, 3 and 4 are self-assembled in supramolecular dendrimers
resembling spherical micelles when they are centered at the corners and the body-center and respectively highly
1
3
rounded tetrahedra when they are at /4 and /4 distance along one of the bisectors of each face of the cubic cell.
This novel thermotropic LC phase is similar to that of the lyotropic Pm3hn phase of biological lipids. These
supramolecular dendrimers contain a poly(benzyl ether) core dispersed in an aliphatic matrix of nearly uniform
density which is made up of the melted terminal long alkyl chains of the monodendrons. The size of the supramolecular
dendrimer and of the entire unit cell increases with generation number as a result of a disproportionately large
increase in the number of AB3 repeat units relative to the number of terminal alkyl chains in a monodendron which
decreases its average cone angle. The present experiments provide the first examples of monodendrons which self-
assemble into spherical supramolecular dendrimers forming a thermotropic cubic LC phase.
Introduction
method4 for their preparation initiated efforts toward the
development of accelerated synthetic techniques based on
covalent5 and supramolecular6 chemistry approaches for the
preparation of monodendrons and dendrimers. It is well
accepted that dendrimers exhibit a spherical shape in solution.1
However, less is known about their shape in melt and solid states
although most of their new and unusual physical properties and
functions in these states are determined by their shape. Various
indirect techniques which cannot easily discriminate between
single species and aggregates have strongly suggested that in
solid and melt states dendrimers can adopt either spherical1,6b,7
or rodlike shapes.1,7c,8
The discovery and subsequent expansion of research on
dendrimers1 produced a dramatic increase of our synthetic
capabilities to design building blocks which enable for the first
time the construction of complex macromolecular and supramo-
lecular systems with controlled architectures, predictable and
well defined shapes, functions, properties, and nanoscopic device
fabrication potentiality.2,3 The elaboration of the convergent
* Corresponding author: Phone: 216-368-4242. Fax: 216-368-4202.
e-mail: vxp5@po.cwru.edu.
† The University of Sheffield.
‡ Case Western Reserve University.
X Abstract published in AdVance ACS Abstracts, February 1, 1997.
(1) For reviews on dendrimers, see: (a) Tomalia, D. A.; Durst, H. D.
Top. Curr. Chem. 1993, 165, 193. (b) AdVances in Dendritic Macromol-
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S0002-7863(96)03295-7 CCC: $14.00 © 1997 American Chemical Society

1540 J. Am. Chem. Soc., Vol. 119, No. 7, 1997
Balagurusamy et al.
Scheme 1. Schematic Representation of (a) the Self-Assembly of 12-ABG into a Supramolecular Cylindrical Dendrimer and the
Subsequent Formation of the Columnar Hexagonal LC Supramolecular Assembly and (b) the Self-Assembly of 12G2-AG into a
Spherical Supramolecular Dendrimer and the Subsequent Formation of the Cubic LC Supramolecular Assembly
We are elaborating synthetic strategies which provide a
molecular engineering approach to monodendrons and both
macromolecular and supramolecular dendrimers which exhibit
a predictable well defined shape in crystalline, ordered and
disordered melt (i.e., liquid-crystalline and isotropic liquid)
states. This shape is responsible for the formation of an ordered
LC or crystalline assembly which is analyzed by X-ray
diffraction techniques and generates direct information on the
shape and size of the dendrimers and of their internal order.9,10
Cylindrical dendrimers are systematically obtained by polym-
erization or self-assembly of monodendrons which exhibit a
tapered fan shape.10 In conformity with the same hypothesis,
cone-shaped monodendrons should produce Via similar tech-
niques spherical dendrimers.
tively flat tapered and conical shapes. Flat tapered monoden-
drons are produced from 3,4,5-tris(4-alkyl-1-oxy)benzyloxy-
benzoate (12-ABG where G stands for gallate) building blocks
(Scheme 1a), while 3,4,5-tris[3,4,5-tris(alkyl-1-oxy)benzyloxy]-
benzoate units should favor the generation of a conical shape
(Scheme 1b). Molecular modeling of the monodendrons from
Scheme 1 demonstrated that monosubstitution of their external
benzyl ethers with alkyl groups only in the 4-position permits
their independent free rotation about the benzyl ether bond.
Consequently, these monodendrons can be fitted into a flat
tapered shape (Scheme 1a). Substitution of the same benzyl
ethers with alkyl groups in their 3,4,5-positions (Scheme 1b)
allows only a restricted-cooperative rotation which requires the
two external benzyl ethers to be approximately orthogonal to
the internal one. This cooperative rotation favors a conical
shaped monodendron. In addition, these architectural differ-
ences also produce a different curvature on the external surface
of the corresponding monodendron. Interfacial curvature plays
an important role in the formation of lyotropic and related
thermotropic LC phases.11-18 A detailed discussion of the
geometrical aspects of lyotropic LC phases which supports the
Scheme 1 outlines the strategy developed in our laboratory
for the rational design of monodendrons which exhibit respec-
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Spherical Supramolecular Dendrimers
J. Am. Chem. Soc., Vol. 119, No. 7, 1997 1541
Scheme 2. Synthesis of 3,4,5-t-12Gn-AG-CH3 and 3,4,5-t-12Gn-AG-CH2OH
rationalization of the molecular design and the observed phase
behavior of the monodendrons reported in this publication is
available in the Supporting Information.14-29 In contrast to the
abundance and biological significance of lyotropic systems
which exhibit cubic symmetry15b,18,19,20 relatively few thermo-
tropic systems which display similar phases21-29 are known.
This publication reports the rational design, synthesis, and
characterization of the first four generations of monodendrons
which, as a function of generation number, exhibit conical and
respectively hemispherical shapes. These monodendrons self-
assemble into supramolecular dendrimers which display a
spherical shape that generates a novel thermotropic cubic LC
phase which was analyzed by X-ray diffraction and provided
the first confirmation and quantitative characterization of the
widely suspected spherical shape of dendrimers in an ordered
melt state.
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columnar phases in a class of side-chain polymers; 15th International Liquid
Crystal Conference, Budapest, 3-8 July 1994; in preparation.
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1996, 237.
Results and Discussion
Synthesis of Monodendrons. Our approach to the synthesis
of benzyl ether type monodendrons is based on the use of a
polyhydroxy methyl benzoate building block. The size and
shape of the monodendron at each generation is determined by
the number (1, 2, or 3) and position (3,4-, 3,5- or 3,4,5-) of the
reactive hydroxyl groups of the methyl benzoate. Nucleophilic
substitution of the hydroxylic groups of polyhydroxy methyl-
benzoate with an appropriate electrophile determines the surface
functionality (R in Scheme 2) of the monodendron. In this
investigation we used the AB3 monomer methyl 3,4,5-trihy-
droxybenzoate (methyl gallate) and its first generation mono-
dendron, methyl 3,4,5-tris(n-dodecyloxy)benzoate (3,4,5-t-12G1-
AG-CH3) where 3,4,5- refers to the position of the alkyloxy
tails of the methylbenzoate (i.e., methyl gallate is AG-CH3)
ring and t to the number of alkyl tails (t ) tris, b ) bis, m )
mono). The prefix 3,4,5-t- will no longer be referred to in this
discussion as it remains consistent throughout. The number
preceding the letter G (from gallate) refers to the number of
carbon atoms in the linear alkyl tails, while the number following
G refers to the generation number.
Scheme 2 outlines the convergent4 stepwise synthesis of the
second (G2), third (G3), and fourth (G4) generation monoden-
(29) Chandrasekhar, S.; Shadashiva, B. K.; Suresh, K. A. Pramana 1977,
9, 471.

1542 J. Am. Chem. Soc., Vol. 119, No. 7, 1997
Balagurusamy et al.
Table 1. Theoretical and Experimental Molecular Weights Determined by MALDI-TOF MS and GPC and Thermal Transitions of
Monodendrons 12Gn-AG-CH3, 12Gn-AG-CH2OH, and 12Gn-AGc
thermal transitions (°C) and corresponding enthalpy changes (kcal/mol)
m/z [M + Na+] Mn Mw/Mn Mn/
monodendron
12G1-AG-CH3
MWt
(MALDI-TOF) (GPC) (GPC) MWt
heating
cooling
689.12
910 1.04 1.32 k 44 (23.2) i
i 4 (15.5) k
k 23 (15.9) i
2448 1.07 1.16 k 57 (37.0) i
12G2-AG-CH3
12G3-AG-CH3
12G4-AG-CH3
12G1-AG-CH2OH
2113.4
6386.4
19205.1
661.11
2136.1
6410.7
i 35 (0.74) Cu 11, 4 (21.9)a k
k 10 (-5.49) k 57 (36.7) i
5872 1.11 0.92 k -13 (22.7) k 39 (8.43) Cu 94 (1.22)i
k -11 (29.2) Cu 94 (1.22) i
i 75 (0.81) Cu 47 (0.85) k -16
(28.0) k
19228.5
11871 1.08 0.62 k -13 (68.7) g 37 Cu 77 ib
i 61b Cu 47 g -17 (76.9) k
k -11 (88.3) g 42 Cu 77 ib
897 1.03 1.36 k 50 (19.7) i
i 37 (11.7) k
k 47 (12.7) i
12G2-AG-CH2OH 2085.4
12G3-AG-CH2OH 6358.3
2108.4
6381.5
2495 1.04 1.20 k 36 (4.31) k 59 (27.4) Cu 88 (1.12) i
i 80 (0.68) Cu -15 (23.3) k
i 93 (0.90) Cu -17 (25.6) k
i 33 (14.1) k
k -8 (7.02) k 38 (-3.18) k 58 (4.96) Cu 88 (0.87) i
5914 1.08 0.93 k -12 (25.0) k 45 (1.84) Cu 107 (1.35) i
k -12 (30.6) Cu 106 (1.22) i
12G1-AG
12G2-AG
12G3-AG
12G4-AG
675.10
2099.4
934 1.06 1.38 k 60 (14.9) i
k 59 (14.3) i
2122.8
6395.3
2632 1.04 1.25 k 85 (25.6) Cu 119 (1.27) i
k -9 (5.62) k 43 (-19.5) k 83 (24.3) Cu 117 (0.96) i
5749 1.13 0.90 k -15 (31.5) Cu 140 (1.63) i
k -12 (29.7) Cu 139 (1.17) i
i 111 (0.87) Cu -15 (8.67) k
i 127 (1.17) Cu -17 (31.0) k
i 72 Cu -18 (89.4) k
6372.3
19191.3
19214.8
11274 1.11 0.59 k -14 (83.3) Cu 85 ib
k -12 (105.9) Cu 85 ib
a Sum of enthalpies from overlapped peaks. b Observed by optical polarized microscopy. c Data from the first heating and cooling scans are on
the first line, and data from the second heating are on the second line.
drons, 12Gn-AG-CH3. The ester group of the first generation
monodendron, 12G1-AG-CH3, was reduced with LiAlH4 to give
the crystalline benzyl alcohol, 12G1-AG-CH2OH, in 93% yield.
Its quantitative chlorination with SOCl2 and a catalytic amount
of DMF produced the benzyl chloride, 12G1-AG-CH2Cl, in
91% yield. This compound was isolated by aqueous workup
followed by recrystallization from acetone. However, in
subsequent generations the benzyl chlorides were used without
further purification.
within a few minutes (for 12Gn-AG-CH2Cl) to several hours
(for 12G2-AG-CH2Cl), the HCl induced cleavage of the highly
activated p-alkoxybenzyl ether moieties was observed in the
1H NMR spectrum. An excess of Et3N or other similar organic
bases retarded the decomposition but did not completely
suppress it. When the chlorination was carried out in the
presence of an excess of the non-nucleophilic base scavenger,
2,6-di-tert-butylpyridine, which is known to be an extremely
eficient proton-trap,31 no decomposition products were observed
even after several days in solution or months in solid state.
Optimization of the reaction conditions revealed that the
chlorination proceeded equally well when a stoichiometric
amount of 2,6-di-tert-butylpyridine was used. The chlorinated
product could be used after aqueous workup in the next step
without further purification.
Previous work in our10 and other30 laboratories demonstrated
the quantitative alkylation of methyl gallate with 3.0 equiv of
p-(n-dodecyloxy)benzyl chloride by using K2CO3 as base in
DMF (65-80 °C, 4-8 h) to generate methyl 3,4,5-tris[p-(n-
dodecyloxy)benzyloxy]benzoate in >90% isolated yields. Un-
der similar conditions, complete alkylation of methyl gallate
with 12G1-AG-CH2Cl was accomplished in 3.5 h at 65 °C to
give the second generation monodendron, 12G2-AG-CH3, in
88% yield after purification by column chromatography (b.
Al2O3, CH2Cl2). The complete consumption of 12G1-AG-
CH2Cl was monitored by the disappearance of the benzylic
-CH2- protons at 4.47 ppm in the 1H NMR spectrum.
Quantitative reduction of 12G2-AG-CH3 with LiAlH4 produced
12G2-AG-CH2OH in 91% yield after recrystallization from
acetone.
The alkylation of methyl gallate with 12G2-AG-CH2Cl was
carried out in NMP at 80 °C due to the limited solubility in
DMF of the starting benzyl chloride. At 80 °C in DMF, the
insoluble benzyl chloride melted, and the interfacial reaction
proceeded smoothly with vigorous stirring. Purification by
column chromatography (b. Al2O3, hexanes) produced 12G3-
AG-CH3 in 73% yield. After reduction with LiAlH4, chlorina-
tion with SOCl2/di-tert-butylpyridine and alkylation of methyl
gallate, 12G4-AG-CH3, was obtained in 33% overall yield from
12G3-AG-CH3. 12G3-AG-CH2OH and 12G4-AG-CH3 were
purified by column chromatography (b. Al2O3). The final
alkylation step required a reaction time of 20 h in NMP at 80
°C. The extent of this reaction was monitored by a combination
Fre´chet et al.4a have described the mild bromination of the
benzylic alcohol moiety of AB2 dendritic wedges with CBr4/
PPh3. While this method proceeds quantitatively in the absence
of side reactions, it suffers from the generation of stoichiometric
amounts of triphenylphosphine oxide byproducts. At higher
generation number, the reaction is considerably slower and
requires an excess of reagents. SOCl2 is the most attractive
reagent for the chlorination of benzyl alcohols due to the short
reaction time, low temperature, low price, and ease of manipula-
tion. In addition, under our reaction conditions, the reactivity
of benzyl chloride is sufficient to produce a quantitative
etherification. The chlorination of 12Gn-AG-CH2OH (n > 1)
with SOCl2 in the presence of a catalytic amount of DMF was
completed within 5-10 min at room temperature. However,
1
of H NMR and GPC analysis.
Monodendrons with a carboxylic acid functionality at their
focal point were prepared by basic hydrolysis of the corre-
sponding esters, 12Gn-AG-CH3. The products, 12Gn-AG,
were obtained after protonation in THF solution with 50%
aqueous acetic or formic acid.
Structural Characterization of Monodendrons. The purity
of all monodendrons was determined by a combination of TLC,
GPC, HPLC, 1H NMR and 13C{1H} NMR spectroscopy,
elemental analysis, and MALDI-TOF mass spectrometry. Table
(30) Maˆlthete, J.; Nguyen, H. T.; Levelut, A. M. J. Chem. Soc. Chem.
Commun. 1986, 1548.
(31) Brown, H. C.; Kanner, B. J. Am. Chem. Soc. 1953, 75, 3865.

Spherical Supramolecular Dendrimers
J. Am. Chem. Soc., Vol. 119, No. 7, 1997 1543
Figure 2. 200 MHz 1H NMR spectra of 12Gn-AG (n ) 1-4) (CDCl3,
TMS, 20 °C).
MWt, the slope of the Mn dependence decreases continuously.
These results are a consequence of the by now well-accepted
tendency of dendrimers and high generation monodendrons to
exhibit a lower hydrodynamic volume than their linear homo-
logues due to their compact architecture.4a,32 The same plot
shows the dependence of Mn/MWt on MWt. The AB3 nature
of the repeat unit of the monodendrons results in the formation
of very compact monodendron structures at the third and fourth
generation.
Figure 1. (a) GPC traces of 12Gn-AG-CH3, 12Gn-AG-CH2OH, and
12Gn-AG (n ) 1-4). (b) Dependence of Mn (O) and the ratio, Mn/
MWt (b), Vs. theoretical molecular weight (MWt) of 12Gn-AG (n )
1-4).
1 summarizes the theoretical molecular weights (MWt), the
absolute molecular weights determined by MALDI-TOF MS,
relative number-average molecular weight (Mn) determined by
GPC with polystyrene standards, and the ratio Mn/MWt for
12Gn-AG-CH3, 12Gn-AG-CH2OH, and 12Gn-AG. The cor-
responding GPC traces are shown in Figure 1a. All monoden-
drons are monodisperse and show monomodal molecular weight
distribution. The large increase (>3-fold) in molecular weight
with generation number guarantees excellent resolution of lower
molecular weight fragments arising from incomplete alkylation
reactions. These fragments are not observed in the GPC/HPLC
traces from Figure 1a.
MALDI-TOF mass spectra of 12Gn-AG-CH3, with n ) 2,
3 and 4, 12Gn-AG-CH2OH, with n ) 2 and 3, and 12Gn-AG,
with n ) 2, 3, and 4, gave the correct molecular peak (Table 1
and Supporting Information). Lower mass fragments which do
not correspond to intermediary compounds were observed in
small amounts in several cases of low generations monoden-
drons. Their origin will be discussed in a full report on the
MALDI-TOF MS characterization of these and other mono-
dendrons and dendrimers.
NMR Analysis. The reaction sequence (a) LiAlH4 reduction,
(b) SOCl2 chlorination, and (c) alkylation for each generation
was quantitatively monitored by observation of the formation
and consumption of benzylic CH2OH and CH2Cl protons.
Regardless of the generation number, the benzylic CH2OH
protons were observed as an easily distinguishable doublet
shifted about 0.1 ppm downfield from the benzylic CH2Cl
protons. During the transformation from 12G3-AG-CH2Cl to
12G4-AG-CH3, the signal arising from CH2Cl was somewhat
broadened and of low sensitivity; therefore, GPC analysis was
1
used as a complementary technique. The combination of H
and 13C{1H} NMR techniques was used to verify the structural
purity of the monodendrons as well.
Figure 2 shows the 1H NMR spectra of the series of
carboxylic acid functionalized monodendrons, 12Gn-AG. The
chemical structure of the outermost tier of the monodendron is
also drawn with the protons labeled Ha-Hf. The central benzene
unit of each monodendron is defined as tier 1 (T1), and at each
generation a new tier (Tn) is formed with three times larger
Figure 1b plots the dependence of the Mn of 12Gn-AG
determined by GPC on its MWt. Mn increases nonlinearly with
the increase in absolute molecular weight, MWt. At higher
(32) Tomalia, D. A.; Naylor, A. M.; Goddard, W. A., III Angew. Chem.,
Int. Ed. Engl. 1990, 29, 138.

1544 J. Am. Chem. Soc., Vol. 119, No. 7, 1997
Balagurusamy et al.
number of benzene rings than in the previous tier. The aromatic
protons are labeled Hf, and the benzylic protons on position 1
of the aromatic ring are labeled He. The position of an aromatic
or benzylic proton within the monodendritic structure can be
pinpointed by the tier to which it belongs and its attachment to
the oxygen atom (meta or para) of the aromatic ring from the
previous tier. The former is indicated in parentheses (T1, T2,
T3, or T4). Resonances arising from substitution in the para
position are distinguished from meta substituents by a prime
(′) superscript. The methylenic protons of the alkyl tails are
always located on the periphery of the monodendron, and,
therefore, only their meta or para substitution pattern is
1
specified. With increasing generation number, the H NMR
signals of 12Gn-AG begin to broaden significantly, and nearly
all resolution is lost in the spectrum of 12G4-AG. The broad
signals of 12G4-AG are attributed to the extremely dense packed
structure of the monodendron arising from the AB3 substitution
pattern and the high alkyl tail density generated at the periphery.
As a consequence, internal conformational mobility is reduced
to such an extent on the NMR time scale that broadened signals
arise from the individual contributions of all available confor-
mations.
The 1H NMR spectrum of the third generation monodendron
12G3-AG contains the most accessible information, since the
effect of the dense packing within the dendritic structure can
be rationalized by the identification of the well-resolved NMR
signals arising from protons on three different tiers. From the
assignments in Figure 2 we concluded that the aromatic and
benzylic protons near the periphery (T3) of the monodendron
are shifted to higher field. An opposite behavior has been
observed in other monodendrons.4a
The 13C{1H} NMR spectra of 12Gn-AG, shown in Figure
3, were used to confirm the 1H-NMR assignments. The
aromatic carbons are labeled C-1, C-2, C-3, or C-4 based on
their ring position. The benzylic carbons are labeled Hh and
Hh′ based on meta- and para-attachment as described previously.
The spectrum of 12G3-AG displays strong signals from C-2 at
105.8, 107.2, and 110.0 ppm. They were assigned to C-2 of
T3, T2, and T1, respectively, based on their expected decrease
in signal intensity. The aromatic carbons at the periphery (T3)
are shifted 1.4 ppm upfield of the internal T2 carbons and are
therefore shielded. This shielding is due to the through-space
interaction of the C-2 nucleus with the anisotropic shielding
zone of the adjacent aromatic rings in the densely packed
monodendron. Inspection of C-1, C-3, and C-4 of 12G3-AG
supports this conclusion. The carbons from T1 are neglected
due to the susceptibility of their chemical shifts to electronic
effects arising from their attachment to the carboxylic acid
functionalized aromatic ring. Carbons C-1 and C-4 are further
from the anisotropic shielding zone of the adjacent aromatic
rings and show a difference of only 0.4 ppm in their chemical
shifts from T3 and T2. C-3 shows only one strong peak
corresponding to the overlapped resonances from all of the C-3
protons, regardless of which tier they belong to. Any shielding
of the peripheral C-3 carbons is negated by the electronic effects
arising from the vicinal oxygen atom. This shielding effect is
a consequence of the cone-shaped geometry of the monoden-
dritic exo-receptor and can be understood by inspecting the 1H
NMR spectrum of 12G2-AG and of several model compounds.
A detailed discussion is available in the Supporting Information.
Figure 3. 50 MHz 13C{1H} NMR spectra of 12Gn-AG (n ) 1-4)
(CDCl3, 20 °C).
requires the relative orthogonal arrangement mentioned above.
In the case of 12ABG free random rotation of the three benzyl
ethers is allowed. The cooperative rotation of the benzyl ether
groups of the 12Gn-AG is dictated by the presence of the two
alkyloxy groups in the 3,5 positions of the 12G1-AG. The
methylenic protons, He′′ (from Figure 2 of Supporting Informa-
tion), are situated within 4-5 Å of the nuclei of the flanking
aromatic rings. The side view dramatizes the cone shape of
this monodendron (Scheme 1, Figure 4).
Thermal Analysis. The phase behavior of the monodendrons
12Gn-AG-CH3, 12Gn-AG-CH2OH, and 12Gn-AG was char-
acterized by a combination of thermal optical polarized mi-
croscopy and differential scanning calorimetry (DSC). This
phase was assigned based on X-ray analysis, and its structure
will be described in detail in the next section. A detailed
discussion of the DSC traces is presented in the Supporting
Information. The phase behavior of 12Gn-AG is summarized
in Table 1. 12Gn-AG-CH2OH with n ) 2 and 3 and 12Gn-
AG-CH3 with n ) 3 and 4 display an enantiotropic cubic LC
phase, while 12G2-AG-CH3 shows only a monotropic cubic
phase. 12G1-AG-CH3 and 12G1-AG are only crystalline. On
the optical polarized microscope the cubic phase is as expected
optically isotropic.
Determination of the Shape and Size of the Supramo-
lecular Dendrimers by X-ray Analysis of Their Cubic LC
Phase. Only a diffuse ring with a maximum corresponding to
a Bragg spacing of 4.7 Å was observed in the wide-angle region
for the cubic phase of all compounds. A considerable number
of sharp low-angle reflections were recorded for monodendrons
12G2-AG and 12G3-AG. The low-angle powder diffractogram
of 12G2-AG in the cubic phase is shown in Figure 4a of
Molecular models of the top and side views of 12G2-AG
are shown in Figure 4. The flanking aromatic rings are rotated
around their CAr-CH2 bonds and situated orthogonal to the
central aromatic ring. Free rotation of the benzyl ether groups
in 12Gn-AG is allowed only in a cooperative way which

Spherical Supramolecular Dendrimers
J. Am. Chem. Soc., Vol. 119, No. 7, 1997 1545
absence of reflections (111), (113), and (221). The observed
reflections satisfy the conditions for space groups Pm3hn and
P4h3n, namely, 00h: h ) even and hhl: l ) even. Hence, in
accordance with convention, the space group with the highest
symmetry, Viz. Pm3hn, is chosen for the present cubic phase
(the other space group does not possess a center of symmetry).
An LC cubic phase with this symmetry is also known to form
in some Type I lyotropic biological lipid systems.17
Reconstruction of Electron Density Maps. In order to
resolve the structure of the cubic phase, we first calculated the
electron density maps of the unit cell using the observed
diffracted intensities. The correct choice of phase for individual
reflections was reached by a process of elimination, assuming
the tendency for phase separation between aromatic and aliphatic
moieties, which is generally believed to be a primary cause of
formation of most thermotropic layered, columnar and cubic
phases.33
The volume fractions of the aromatic region (the core region
of the molecule including the carboxylic group) and of the
aliphatic region were obtained by computing the volume
enclosed by the van der Waals surface of the respective regions
of the molecule and assuming that the packing fractions are
the same for the two regions. For compounds 12G2-AG, 12G3-
AG, and 12G4-AG the volume fractions occupied by the
aromatic region are, respectively, 18, 19, and 20% of the total
volume. The electron density of a given region is computed
by summing the electrons contributed by each atom in the region
and dividing the sum by the van der Waals volume. The same
space-filling efficiency (packing coefficient) is assumed for both
the aliphatic and aromatic regions. The electron density of the
aromatic region estimated in this manner is 1.5 times that of
the aliphatic region.
Figure 4. Molecular models of 12G2-AG. Top: front view, bottom:
side view.
Table 2. Measured (dexp) and Calculated (dcalc) d-Spacings and
Integrated Intensities (I) (Lorentz and Multiplicity Corrected) of the
Cubic Phase Generated by 12Gn-AG
12G2-AG at
105 °C dexp (Å)/
dcalc (Å)/I
12G3-AG at
80 °C dexp (Å)/
dcalc (Å)/I
12G4-AG at
20 °C dexp (Å)/
dcalc (Å)/I
reflection
100
110
111
200
210
211
220
221/300
310
311
222
320
321
400
48.76/48.29/0.05 56.1/56.00/0.05
34.54/34.15/100
30.93/30.54/80
28.28/27.88/66
23.74/24.15/0.7
39.48/39.60/73
35.40/35.42/100 37.70/37.57/100
32.64/32.33/55
28.05/28.00/0.5
41.90/42.00/94
In terms of diffraction experiments, the electron density F(br)
in the cubic phase, as in any periodic structure, can be expressed
as a Fourier series, the coefficients of which are the structure
factors Fhkl corresponding to the individual reflections. In
general
34.30/34.29/32
21.29/21.60/0.1
29.40/25.05/0.4
F(br) - F )
F˜hkl exp[-i2π(hx + ky + lz)]
(1)
∑
o
22.08/21.97/0.3
21.09/21.17/0.5
19.87/19.80/1.3
h,k,l
18.19/18.25/0.8
17.00/17.08/3.5
Here F0 is the average electron density and x, y, and z are the
fractional coordinates of a point in the unit cell. F˜ denotes the
generally complex structure factor which can be written as
Supporting Information, and the list of observed and calculated
d-spacings is given in Table 2. In contrast, 12G4-AG gave no
sharp reflections unless it was cooled slowly (1 °C/h) from the
isotropic phase. Even in the latter case it gave only three
reflections which corresponded closely to the strongest reflec-
tions observed in 12G2-AG and 12G3-AG. The reflections
from 12G2-AG and 12G3-AG, whose reciprocal d-spacings
F˜hkl ) |Fhkl| exp(iφhkl)
(2)
Whereas the modulus |Fhkl| is given by the square root of
the intensity of the observed reflection, the phase φhkl is
unknown. However, if the lattice is centrosymmetric, the
structure factor becomes real, and the phase is restricted to only
x
x
x
x
x
x
x
x
x
were in the ratio 2: 4: 5: 6: 8: 10: 13: 14: 16:...,
could be indexed on the primitive cubic lattice (a ) 68.3 Å for
12G2-AG and a ) 79.2 Å for 12G3-AG) with the first
reflection assigned the index (110) (Table 2). The three
reflections of 12G4-AG are indexed as (200), (210), and (211),
giving the unit cell parameter a ) 84.0 Å. In view of the
similarity in the diffractograms from the G2, G3, and G4
compounds, their structure is regarded as isomorphous. The
absence of higher order reflections in 12G4-AG is attributed
to its higher positional disorder.
one of the two allowed values, 0 and π, thus making Fhkl
)
(|Fhkl|. The problem of our structure determination therefore
essentially reduces to finding the correct sign, or phase, of F
for each X-ray reflection.
For the specific case of Pm3hn cubic symmetry eq 1 is reduced
to the cosine series of the following form:
F(br) - F )
Fhkl cos(2πhx) cos(2πky) cos(2πlz) (1)
∑
o
h,k,l
Diffraction patterns from monodomains of 12G2-AG re-
corded along a 100 direction (Figure 4b of Supporting
Information) show the presence of reflections (410) and (420)
which are not seen in the powder pattern. Reflection (300) is
absent, in agreement with the powder pattern. Monodomain
patterns recorded along 110 and 210 clearly demonstrate the
We start the X-ray analysis with the compound 12G4-AG
since its higher disorder in the cubic phase results in fewer
(33) (a) Skoulios, A.; Guillon, D. Mol. Cryst. Liq. Cryst. 1988, 165, 317.
(b) Skoulios, A. Makromol. Chem., Macromol. Symp. 1992, 62, 201. (c)
Ungar, G.; Abramic, D.; Percec, V.; Heck, J. A. Liq. Cryst. 1996, 21, 73.
(d) Cistola, D. P.; Small, D. M. J. Am. Chem. Soc. 1990, 112, 3214.

1546 J. Am. Chem. Soc., Vol. 119, No. 7, 1997
Balagurusamy et al.
Table 3. Characterization of Supramolecular Dendrimers Self-assembled from 12Gn-AG Monodendrons
cubic lattice
dimension, monodendrons
a (Å)b
no. of
no. of
monodendrons per
distance from vacancies distance from carboxylic
at positions d to centers hydrogen to the end of
density,
monodendron d20 (g/cm3) T (°C)
per unit cell, µ′ c spherical dendrimer, µd of nearest dendrimer (Å) extended dodecyl chain (Å)
12G2-AG 0.99 (1.04)a 105 68.3 ( 0.4
90.0 (96)
46.2 (48.0)
15.2 (16.0)
11.3 (12.0)
5.8 (6.0)
1.9 (2.0)
24
28
30
26
32
37-38
12G3-AG 0.99 (1.04)a
12G4-AG 0.99 (1.04)a
80 79.2 ( 0.4
20 84.0 ( 0.3
b
a Assumed. a ) ( 2‚d110
+
+
+
+
8‚d220)/5. c µ′ ) (a3/d)/M. d µ ) µ′/8.
x
x
4‚d200
x
5‚d210
x
6‚d211
x
observed diffraction lines, compared with 12G2-AG and 12G3-
AG. Using the observed strong reflections ((200), (210), and
(211), see Table 2), we have computed the electron density
profiles in the cubic unit cell. The 23 ) 8 independent choices
for the phases of these three reflections are reduced by half when
the arbitrary choice of origin is allowed for. Out of the
remaining four, two are related to the other two by inversion
with respect to F0.
In all three compounds studied these three reflections would
capture the main coarse features of the electron density map.
However, in compounds 12G2-AG and 12G3-AG the exclusion
of higher reflections would mean an arbitrary truncation of the
Fourier series. This would result in artefacts which could be
rectified only by the inclusion of higher terms, with their correct
sign, arising from all remaining reflections of reasonable
intensity. In contrast, the “artifact” in the electron density
distribution computed for 12G4-AG is only in that the distribu-
tion would be smeared by averaging over a disordered lattice.
If the disorder was thermal-like, the smearing could be taken
account of by a Debye-Waller factor. While the electron density
profile obtained from the diffractogram of 12G4-AG will be
more rounded than that of a typical individual unit cell, it will
be basically correct, provided the correct phase choice for the
three independent strong reflections is made. The profile
resulting from such a naturally truncated series will then serve
as a guide in selecting the correct phase choices for the larger
number of reflections in the case of compounds 12G2-AG and
12G3-AG.
The electron density profiles have been computed for all four
combinations of phases, namely “+ - ++”, “++ - -”, “- + -
-” and “- - ++”. The signs correspond to reflections (200),
(210), (120), and (211), respectively.34 The profiles are
discussed further below. To help decide on the viability of a
particular phase combination, electron density histograms were
calculated for the above phase choices.
Electron Density Histograms. The histograms were ob-
tained by dividing the unit cell into a large number (106) of
small cells, counting the volume fraction of cells that have the
electron density within a given interval (F, F+δF), and plotting
these volume fractions against electron density. Such histo-
grams have been used in the past.18a We use them to determine
which combinations of structure factor phases give rise to good
separation between the high- and low-density regions, while
maintaining a volume ratio consistent with that calculated from
the molecular model. In the ideal case of complete separation
into two discrete phases we would expect the histogram
corresponding to the correct phase choice to show a bimodal
distribution of volume. However, there are two factors con-
tributing toward broadening of the observed distribution: (1)
the presence of disorder, i.e., the averaging over fluctuations
between individual cells resulting in apparent blurring of phase
boundariesssee above and (2) genuine partial mixing of phases
within individual unit cells.
As mentioned earlier, in the particular case of 12G4-AG,
model calculations show that the high electron density phase
(aromatic region including the carboxylic group) occupies 20%
of the volume, while the low-density aliphatic phase occupies
the remaining 80%. In the ideal case we would thus expect
the histogram to consist of two peaks, with a 20:80 ratio between
the areas of the high-density and the low-density peak. Such a
histogram would be an indication of the correct choice of the
structure factor phase combination and, hence, of the underlying
structural model. However, we expect a certain degree of
smearing of the observed distributions due to the two factors
outlined above.
Figure 5 shows electron density histograms, calculated from
the intensity data for the cubic phase of 12G4-AG, for the four
distinguishable phase combinations. The dashed vertical line
is the demarcation between the low density 80% and the high
density 20% of the total volume. As is seen, the histogram for
the phase combination “- + - -”(Figure 5c) is the inverse of
the histogram for “+ - ++” (a), and similarly histogram “- -
++” (Figure 5d) is the inverse of histogram “++ - -” (Figure
5b). The “inverse” phase combinations “- + - -” and “- -
++” can be safely excluded at this stage since the demarcation
line cuts through the peak of the histogram or near it, rather
than through a trough. These distributions do not meet the
expectation of a clean separation of aliphatic chains into an 80%
volume fraction region of low and constant33c density. On the
other hand, the histograms labeled “+ - ++” and “++ - -”
show that both these combinations are worth investigating
further. However, already on the basis of the appearance of
the histograms, our preferred choice is “+ - ++” since the large
narrow peak on the low-density side indicates the expected
uniform density of the aliphatic phase. Next we investigate the
electron density profiles of the unit cell for the two phase
combinations, “++ - -” and “+ - ++”.
Columnar Model. The electron density profiles of the unit
cell for the phase combination “++ - -” are shown in Figure
1
1
6a at elevations z ) 0, z ) /4, and z ) /2. Electron density
shows continuous ridges, corresponding to linear high-density
regions or columns, in the zero and half level sections. A third
set of columns, this time vertical, can be traced through all three
sections in Figure 6a at positions x ) 1/2, y ) 0 (with x-axis on
the right and y-axis on the left). Thus, according to this model,
the structure essentially consists of three mutually perpendicular
sets of parallel columns which represent the high electron density
regions (aromatic parts) of the molecules. The high-density
regions are shown schematically in the model representation
of the unit cell in Figure 6b. The three sections at levels z )
0, 1/4, and 1/2 are indicated for easy comparison with Figure 6a.
An isolated column is shown separately at the bottom of Figure
(34) Although the intensity of (hk0) and (kh0) (in general, (hkl) and (khl))
reflections are equal for the Laue group of the space group Pm3hn the point
group symmetry of the space group requires these reflections to have the
same or opposite phase depending on whether the sum is even or odd,
respectively. Hence the reflections (210) and (120) are treated separately
with opposite phases but the same intensity. Accordingly the higher order
reflections, (321) and (231), that occur in the electron density computations
for the 12G2-AG are treated separately with the same phase and intensity.
It appears that in the studies of lyotropic systems this distinction has not
been made (Luzzati, V.; Vargas, R.; Mariani, P. J. Mol. Biol. 1993, 229,
540).

Spherical Supramolecular Dendrimers
J. Am. Chem. Soc., Vol. 119, No. 7, 1997 1547
Figure 5. Histograms of electron density distribution for 12G4-AG. Calculation was based on the intensities of reflections (200), (210), (120), and
(211) with the respective phase combinations: (a) + - ++, (b) ++ - -, (c) - + - -, and (d) - - ++.
Figure 6. (a) Electron density profiles for 12G4-AG corresponding to the “columnar” model. They are shown at three elevations: z ) 0, 1/4, and
1/2. In this and subsequent electron density diagrams the x-axis is on the right and the y-axis is on the left hand side. (b) Schematic drawing of the
columnar model of the cubic structure. The shaded volumes are the high electron density zones. The edges of the unit cell are shown. An isolated
column is shown below.
6b. It consists of segments which are flattened alternatively in
one of the two mutually perpendicular transverse directions. The
electron density along the spine of the column is nearly constant.
We refer to the above molecular organization as the columnar
cubic model.
If this model was the correct one, the aromatic portions of
the 12G4-AG monodendrons would form infinite continuous
columns, surrounded by an aliphatic matrix. However, this is
difficult to visualize considering the architecture of 12G4-AG
monodendrons. Furthermore, as there are 16 12G4-AG mono-
dendrons and 6 column segments per unit cell, each segment
would contain 22/3, i.e., a noninteger number, of 12G4-AG
monodendrons. These two points suggest that 12G4-AG is
unlikely to form the columnar cubic structure. In fact over-
whelming evidence supports the alternative model, as outlined
below.

1548 J. Am. Chem. Soc., Vol. 119, No. 7, 1997
Balagurusamy et al.
1
1
Figure 7. (a) Electron density profiles for the micellar model of 12G4-AG at z ) 0, /4, and /2. (b) Schematic drawing of the unit cell in the
micellar model showing the positions of the high electron density regions as spheres. Black spheres at the corners and at the body center of the
1
3
cubic unit cell are centered on special positions a. Grey spheres at /4 and /4 positions along face bisectors are centered on special positions c.
Spherical Micellelike Model. The computed electron den-
sity profile for the second phase choice, “+ - ++” (Figure 7a),
shows large maxima (aromatic regions) at the corners and the
body-center (special position a35 ) of the unit cell. In addition,
it has large very similar maxima along one of the bisectors of
density profiles as well as on grounds of the integer number of
12G4-AG monodendrons per structural unit (spherical micelle).
Further structural details derived from the richer diffraction
pattern from compounds 12G2-AG and 12G3-AG corroborate
the validity of this model, as described in the next section.
In the micellar model, “+ - ++”, the special positions where
the electron density has large maxima, i.e., corners, body-center,
and 1/4 and 3/4 positions along one of the bisectors of each face,
coincide with the positions of biological lipid micelles (sphero-
cylinders) for the type-I (lipid-in-water) lyotropic cubic phase
with the same symmetry Pm3hn.17,34-37 It has been proposed36,37
that the elongated micelles located at the corners and the body
center of the unit cell (special position a) are dynamically
disordered giving rise to a spherical electron density distribution.
However, such motion would appear unlikely in a closely-
packed thermotropic system.
Detailed Structure of the Spherical Supramolecular Den-
drimers Self-Assembled from 12G2-AG and 12G3-AG
Monodendrons in their Cubic LC Phase. Having opted for
the spherical micellar model on the basis of the strong reflections
of 12G4-AG, we proceed by analyzing the diffraction data for
12G2-AG and 12G3-AG which contain a larger number of
reflections (Table 2). The diffractograms and the corresponding
electron density maps of the latter two compounds are very
similar and thus the common structure will be discussed here
on the example of 12G2-AG. Altogether six reflections, i.e.,
all those with significant intensities, were included in the
calculation of electron density profiles. In addition to the strong
reflections (200), (210), and (211), these now include (220),
(321), and (400). As before, the three new reflections provide
eight independent choices (but see endnote and ref 34, this time
with reference to reflection (321)). All eight possible phase
1
3
each face at the positions /4 and /4 (special position c). The
three-dimensional contours of the electron density maxima are
to a first approximation spherical (see further below for details).
The high electron density regions are shown as spheres in the
model representation of this structure in Figure 7b. The two
types of spheres, on special positions a and c, are shown as
black and grey, respectively. Thus, according to this second
model, the aromatic moieties cluster around these special
positions forming discrete micelles of nearly spherical average
shape embedded in aliphatic continuum (micellar model). There
are two micelles at positions a (black) and six at positions c
(grey) per unit cell. There are two 12G4-AG molecules per
micelle (Table 3).
The narrow low-density peak in the histogram (Figure 5b)
for this second phase choice is consistent with the intermicellar
volume, occupied by aliphatic chains, having nearly constant
density. This is illustrated by the large almost flat area between
the peaks in the z ) 1/4 profile in Figure 7a. The reason for the
absence of the expected distinct high-density peak in the
histogram is also apparent from the appearance of the profiles:
compared with the majority (80%) aliphatic phase, the minority
(20%) aromatic phase is far more affected by the smearing
associated with positional disorder (see above). Therefore the
small high-density plateau regions expected in Figure 7a at the
centers of the micelles are rounded off, and only a broad
shoulder rather than a discrete peak is observed in the histogram
(Figure 5b).
The spherical micellar model is our preferred choice on
grounds of the appearance of the histogram and the electron
(36) Fontell, K.; Fox, K.; Hansson, E. Mol. Cryst. Liq. Cryst. 1985, 1,
9.
(37) (a) Eriksson, P.-O.; Lindblom, G.; and Arvidson, G. J. Phys. Chem.
1985, 89, 1050. (b) Eriksson, P.-O.; Lindblom, G.; and Arvidson, G. J.
Phys. Chem. 1987, 91, 846.
(35) International Tables for Crystallography Hahn, Th., Ed.; Kynoch
Press: 1983.

Spherical Supramolecular Dendrimers
J. Am. Chem. Soc., Vol. 119, No. 7, 1997 1549
combinations for these additional reflections were investigated.
One combination, “+ - - -”, stands out in that it does not
distort the electron density map relative to that for 12G4-AG
but instead sharpens its features (here the signs refer, respec-
tively, to reflections (220), (321), (231), and (400)). Electron
1
1
density profiles for the z ) 0, z ) /4, and z ) /2 sections of
the unit cell for the overall phase combination “+ - ++ + - -
-” are shown in Figure 5 of Supporting Information. The
sharper features of these profiles, which are otherwise rather
1
similar to those in Figure 7a, can be best seen in the z ) /4
section.
At this stage it is appropriate to focus on the fine details of
the electron density maps. Thus for example, although the
1
electron density in the intermicellar region at the z ) /4 level
appears reasonably flat, closer examination of the contour map
(see Figure 8a) reveals relatively small but significant deviations
of F from the constant value. This contour map should be
compared with the model in Figure 8b which shows the z ) 1/4
plane in relation to the neighboring micelles. The black solid
circles in Figure 8a coincide with those in Figure 8b, where
1
they mark the intersections of the z ) /4 plane with the lines
connecting the closest pairs of micelles across this plane.
Attention is drawn to the fact that all small maxima or shoulders
(red contours) in Figure 8a coincide with such intersections.
They are thus the result of genuine overlap between spherical
micelles and not random distortions of the map. Similarly, the
presence of minima in F, such as the comparatively deep
minimum at (1/2, 0, 1/4), can be traced to the absence of vicinal
spherical micelles. Such fine details of the electron density
distribution are very sensitive to the phase choice for weak
reflections and the internal consistency of the electron density
map at all levels is a strong indication that the chosen phase
combination is correct.
1
Finer detail of micellar shape can be observed by comparing
the z ) 0 level contour map in Figure 9 with the z ) /4 level
Figure 8. (a) Electron density contour map of the z ) /4 section of
1
the 12G2-AG unit cell for the phase combination “+ - +++ - - -
” (vertical: x-axis, horizontal: y-axis). The solid circles mark the
intersections with the lines joining the nearest micelles at z ) 0 and z
map in Figure 8a. The two crystallographically distinguishable
micellar types indeed have somewhat different shapes. The
micelles, i.e., the high-density regions, situated at the corners
and at the body center of the unit cell (special position a) are
spherical to a good approximation. This is evident from the
circular contours (corners, Figure 9) and the high site symmetry
m3h. On the other hand, micelles at the special positions c lying
on face bisectors have the shape which is best described as
rounded tetrahedron. 4hm.2 is their site symmetry. In Figure 9
the cross-sections through these latter micelles have the shape
of rounded triangles where the apex on the left (right) hand
side of the triangle represents the tetrahedron edge normal to
the figure plane, while the triangle base on the right (left)
represents the tetrahedron edge lying in the figure plane. In
Figure 8a the tetrahedra are rotated by 90° around the [010]
axis, and, accordingly, their central cross-section now has a form
of a rounded square. The tetrahedral micelles are lined up as
antiparallel pairs (ABAB stacking) along the three orthogonal
face-bisector directions.
1
) /2 levels (compare with Figure 10b). The distances between the
micelle centers and the intersection points are shown as fractions of
the cell parameter. Black contours represent negative, and red and other
colors positive relative electron densities. The thick dashed line delimits
the unit cell. (b) Sketch of the lower section of a unit cell showing the
1
z ) /4 plane and the micelles above and below it. The edges of the
unit cell are marked by dashed lines. Darker spheres represent micelles
outside the unit cell. Lines connecting the nearest neighbour micelles
1
across the z ) /4 plane are shown (full lines).
It may be reiterated that the notion of micelles and their
spherical shape refers in these thermotropic systems specifically
to the high-density regions, in this case mainly aromatic. When
aliphatic regions are included the structure should be regarded
in terms of space filling polyhedra. Those polyhedra centered
on positions a (spherical micelles, black circles in Figure 7b)
correspond to distorted dodecahedra (12-hedra) and those
centered on positions c (tetrahedrally distorted micelles, grey
in Figure 7b) correspond to tetrakaidecahedra (14-hedra).38
With more Fourier terms in the electron density summation
(eq 3), the sharper features of the maps for 12G2-AG mean
that the plateau in r at the center of a micelle is flatter than in
the case of 12G4-AG. This results in the histogram of 12G2-
AG (see Figure 6 of Supporting Information) having a sharper
high-density cutoff compared to that in the 12G4-AG histogram
(Figure 5b). The emergence of a clear high-density shoulder,
if not a discrete maximum, is indeed evident in Figure 6 of
Supporting Information.
The reason for tetrahedral distortion of these micelles is most
likely in their tetrahedral coordination. Thus e.g. the micelle
at (1/2, 1/4, 0) (Figure 9) is surrounded by four micelles at (0, 0,
0), (1, 0, 0), (1/2, 1/2, 1/2), and (1/2, 1/2, 1/2). While tetrahedrally
distorted, the micelles lying on face bisectors can, to a first
approximation, still be regarded as spherical.
Figure 9 shows a sizeable maximum in electron density in
the z ) 0 plane at the (0, 1/2, 0) position. This does not
correspond to a micellar site, but there are two micelles directly
above and below this site, each a distance of only 0.25a away;
hence the high maximum in the z ) 0 plane.
(38) Charvolin, J.; Sadoc, J. F. J. Phys. France 1988 49, 521.

1550 J. Am. Chem. Soc., Vol. 119, No. 7, 1997
Balagurusamy et al.
and 12G4-AG are well within 0.01 g cm-3. The density of
0.99 g cm-3 is considered as the lower bound since densification
was found to be a slow process requiring prolonged annealing.
Assuming that monodendrons are equally distributed among all
supramolecular spherical dendrimers or micelles there are,
respectively, 11.3, 5.8, and 1.9 monodendrons per supramo-
lecular micellar dendrimer in 12G2-AG, 12G3-AG, and 12G4-
AG. The latter value strongly suggests that there are in fact
two molecules per micelle in 12G4-AG, a number which is
obtained exactly with a density of 1.04 g cm-3. In fact, if this
density is assumed for all compounds studied, integer numbers
of monodendrons per supramolecular spherical dendrimer or
micelle are obtained in all cases (values in brackets in Table
3).
Similarities between Thermotropic and Lyotropic Sys-
tems. This study has confirmed the validity of the hypothesis
put forward in the Introduction by demonstrating that systematic
variation in the molecular architecture of the monodendron can
change the shape of the supermolecule generated by their self-
assembly from column to spherical and of the resulted phase
from columnar hexagonal to cubic. The primary factor effecting
this change is the transition from flat tapered to conical
monodendron. Thus while compounds of the flat tapered shape
type (Scheme 1) (12ABG) invariably form the hexagonal
columnar LC phase,10 the equivalent compound 12G2-AG,
being more conical, shows the LC micellar cubic phase. By
analogy with inverse lyotropic LC phases, the conical mono-
dendron can be expressed as the mean curvature cm of the
aromatic-aliphatic interface being increasingly negative. While
discussing the analogy with lyotropic phases, we notice in
passing that the Pm3hn cubic phase has never been observed in
inverse (Type II) lyotropics. So far the only observed Type II
cubic phase, i.e., one in which aliphatic chains form the
continuous matrix, is of Fd3hm symmetry.18b
Figure 9. Electron density contour map of the z ) 0 section of the
12G2-AG unit cell for the phase combination “+ - +++ - - -”
(vertical: x-axis, horizontal: y-axis). The solid circles mark the
1
intersections with the lines joining the nearest micelles at z )
/
4
(compare with Figure 10b). The distances between the micelle centers
and the intersection points are shown. Black contours represent negative,
and red and other colors positive relative electron densities. The thick
dashed line delimits the unit cell.
Correlation between Monodendron Generation and Size
of Supramolecular Spherical Dendrimer. To the extent that
the molecular building blocks forming columnar structures can
be described as flat tapered or fan-like 12-ABG (i.e., 4-m-
12G2AG, i.e., Scheme 1a),10 in the present cubic phase the
building blocks responsible for the generation of spherical
micelles may be regarded as conical 12G2-AG (i.e., 3,4,5-t-
12G2-AG) and 12G3-AG (i.e., 3,4,5-t-12G3-AG) and as
hemispherical in the case of 12G4-AG (i.e., 3,4,5-t-12G4-AG).
It is interesting to compare the numbers of monodendrons
per supramolecular spherical micellar aggregate for the three
generations studied. Comparing first the supramolecular as-
semblies generated from 12G4-AG and 12G3-AG, there are
two monodendrons in a spherical micelle in the former case
and six monodendrons in the latter case (Table 3). The observed
ratio of three between these two cases is expected since this is
close to the ratio of molecular masses and volumes (volume
ratio 3.01). However, the spherical micelles generated from
12G2-AG contain only 12 rather than the expected 18 mono-
dendrons, i.e., only twice rather than three times the number
found in the micelles of 12G3-AG. This is in spite of the fact
that the volume ratio between 12G3-AG and 12G2-AG
molecules is again close to three (precisely 3.03). Consequently
there is a reduction of about one-third in the volume of a micelle
and therefore of the whole unit cell on going from 12G3-AG
to 12G2-AG (see Table 3). We suggest that the smaller than
expected supramolecular micelles obtained from 12G2-AG are
due to the somewhat larger molecular taper in this lower
generation monodendron. The argument is illustrated on
hypothetical two-dimensional examples in Figure 10. Figure
10a shows schematically a 12G2-AG molecule (solid lines)
Figure 10. Schematic two-dimensional representation of (a) a 12G2-
AG molecule (full lines) with an added gallic acid group (dashed)
illustrating the decreased taper angle per G2 unit in 12G2-AG relative
to that in 12G2-AG; (b) a hypothetical two-dimensional micelle with
nine molecules of 12G2-AG or three molecules of 12G3-AG; and (c)
a micelle with six molecules of 12G2-AG.
From the measured macroscopic density and unit cell size
the numbers of monodendrons per cell and per supramolecular
spherical dendrimer or micelle have been calculated as shown
in Table 3. The first set of values in the table (outside brackets)
refer to the density of 0.99 g cm-3 measured for 12G2-AG.
Assuming that volume contributions from the aromatic and the
aliphatic regions of the molecule are additive, it can be easily
shown that the density variation between 12G2-AG, 12G3-AG,

Spherical Supramolecular Dendrimers
J. Am. Chem. Soc., Vol. 119, No. 7, 1997 1551
which we may assume to have a taper angle close to 2π/6
radians (thin solid lines); the additional gallic acid present in
the molecule of 12G3-AG is also shown (dashed lines) to
illustrate the reduced taper of each of its three G2 constituents.
Assuming, by way of example, that the conical building block
is reduced from ∼2π/6 to ∼2π/9 radians (dash-dot lines), we
may expect optimal packing in a two-dimensional spherical
micelle to be achieved either with six molecules of 12G2-AG
(Figure 10c) or with nine-thirds, i.e., three molecules, of 12G3-
AG (Figure 10b). Figure 10b also illustrates a large vacancy
which would form in the center of a spherical supramolecular
micelle of 12G2-AG should it have been made up of nine
instead of six molecules (solid lines).
d-set of special positions is equivalent to the c-set, having the
same site symmetry 4hm.2. It is not surprising to find electron
density minima at d if one considers the space filling of the
micellar Pm3hn cubic lattice as a hypothetical two-stage process.
In the first stage the body-centered lattice is established with
the micelles taking up positions a. There remains room for six
more micelles with their associated aliphatic sheaths and either
of the two sets d and c, with six special positions each, is equally
available. As one of the sets is occupied (c) the positions of
the alternative set (d) remain the loci of low density.
As can be seen in Figure 9, density minima as deep as those
at positions d also exist elsewherescf. the six minima sur-
1
rounding the (0, /2, 0) position. All these minima are the
locations where alkyl chain ends (methyl groups) are expected
to be found preferentially (termed chaotic zones by Luzzati and
co-workers).17d The depth of the density minima are considered
to play a key role in determining the stability of the mesophase.39
These vacancies can be found at points where the distance from
the center of the nearest micelle is greatest. For example the
distance between a position d and the center of the nearest
micelle is 0.354a, i.e., 24 Å in the case of 12G2-AG. In
comparison, the distance between the carboxylic hydrogen and
the end of an extended dodecyl chain in 12G2-AG is 26 Å,
i.e., only 2 Å larger. It follows that such a chain must be almost
completely extended to reach position d if the carboxylic end
of the molecule is anchored to the micellar center by hydrogen
bonding. The free energy of the system must therefore be
balanced between an energetic space-filling term and an entropic
term which opposes chain extension.40
Geometrical comparison between molecular model dimen-
sions and the distance of the vacancy from nearest-neighbor
micelles have also been made for supramolecular dendrimers
of other generations and the results are shown in Table 3. The
excess molecular length over the micelle-vacancy distance is
seen to increase with increasing generation number. By analogy
the reverse may also be assumed which means that the first
generation monodendrons might be too short to form the Pm3hn
phase. This is believed to be the reason for 12G1-AG not
showing the cubic phase (Figure 3 Supporting Information).
Equally, it may be expected that molecules equivalent to 12G2-
AG but having shorter chains (e.g., decyloxy instead of
dodecyloxy) may also not be able to reach as far as positions d
and thus may not form the present cubic phase. These and other
possibilities are currently being investigated.
Reverting to the real three-dimensional cases, six appears to
be the optimal number of monodendrons for packing into a
spherical supramolecular dendrimer or micelle in the case of
12G3-AG, and, therefore, we associate with these molecule a
taper described by a solid angle close to 4π/6 steradians. The
taper of molecules of 12G2-AG is, however, larger than one-
third of the above value, apparently being close to 4π/12 rather
than to 4π/18. Moving in the direction of higher monodendron
generations, the number of 12G4-AG molecules in a spherical
micelle is only one third that in the case of 12G3-AG (Table
3), suggesting that the 12G4-AG monodendrons are hemispheri-
cal with a solid angle of 4π/2. Analogy with the above
comparison between 12G2-AG and 12G3-AG would in fact
suggest a somewhat lower natural taper of an isolated 12G4-
AG molecule. However, since the choice in the case of 12G4-
AG is limited to either two or three molecules per micelle, the
former is adopted by the monodendron, with the corresponding
taper angle of 4π/2. The fact that this value is not coincident
with the natural taper of 12G4-AG is suggested by the fact
that the cubic phase of the supramolecular dendrimer generated
from two 12G4-AG does not form readily and that its formation
requires elaborate and prolonged thermal treatment. Qualitative
comparison shows that cubic phase formation rates are equally
high in 12G3-AG and 12G2-AG and substantially lower in
12G4-AG. This suggests that the match between the natural
taper and that adopted in a micelle (integral fraction of 4π) is
good for both of the former but rather poor for the latter
compound. The substantially lower clearing temperature of the
cubic phase of 12G4-AG relative to that of 12G2-AG and
12G3-AG (Table 1) also indicates a lower stability and thus
poorer packing in the cubic phase resulted from 12G4-AG.
Driving Force for Self-Assembly. A self-assembly event
can be dominated by a single molecular recognition process
based on directional and attractive forces such as hydrogen
bonding, van der Waals, electrostatic, and hydrophobic interac-
tions. However, these processes are cooperative, and their
cooperative contribution could be equally important not only
in the aggregation process but also particularly in the stabiliza-
tion of a particular architecture.41 Previous experiments from
our10 and other laboratories6 have demonstrated the use of
hydrogen bonding, electrostatic and van der Waals interactions
to dominate the self-assembly of supramolecular dendrimers
from functional monodendrons. An inspection of the results
from Table 1 reveals that the thermodynamic stability of the
cubic LC phase generated from identical generations of mono-
The above simplified scheme appears to explain the experi-
mentally obtained variation in the number of molecules and
molecular residues per micelle and the variation in unit cell size
with changing monodendron generation. In terms of mean
curvature cm of the aromatic-aliphatic interface, this is directly
related to the molecular shape. The absolute value |cm| is larger
for a molecule of 12G2-AG compared to that for 12G3-AG.
Thus it is also larger for a micelle of 12G2-AG (smaller radius)
compared to that for a micelle of 12G3-AG.
Vacancies. The shapes of the micelles have already been
discussed in the section on detailed structure of 12G2-AG and
12G3-AG. It was established that the micelles at special
positions a (corners and body center) are spherical, while those
on positions c (on face bisectors) are tetrahedrally distorted
spheres. It is also of interest to examine the positions and shapes
of the minima in electron density. As already mentioned, there
is a conspicuous minimum at (1/2, 0, 1/4) (Figure 8a). Its shape
is that of a rounded tetrahedron. This is due to tetrahedral
(39) Seddon, J. M. Biochim. Biophys. Acta 1990, 1031, 1.
(40) Kirk, G. L.; Gruner, S. M.; Stein, D. L. Biochemistry 1984, 23,
1093.
(41) (a) Delaage, M. in Molecular Recognition Mechanisms; Delaage,
M., Ed.; VCH: Weinheim, 1991; p 1. (b) Buckingham A. D. In Principles
of Molecular Recognition; Buckingham, A. D.; Legon, A. C.; Roberts, S.
M. Eds.; Chapman and Hall: New York, 1993, p 1. (c) Schneider, H.-J.
Angew. Chem., Int. Ed. Engl. 1991, 30, 1417. (d) Tanford, C. Science 1978,
200, 1012.
1
1
placement of the four nearest micelles at (1/2, /4, 0), (1/2, /4,
0), (1/4, 0, 1/2), and (3/4, 0, 1/2). It will be noted that this
tetrahedral vacancy is centered on a special position d. The

1552 J. Am. Chem. Soc., Vol. 119, No. 7, 1997
Balagurusamy et al.
dendrons decreases in the following order: 12Gn-AG > 12Gn-
AG-CH2OH > 12Gn-AG-CH3. This stability is indicated by
the corresponding isotropization temperature. The cubic LC
phases generated from these monodendrons are isomorphic, and
more details on this issue will be published elsewhere. There-
fore, the stability of the cubic LC phase is determined by the
stability of the spherical supramolecular dendrimer. This
indicates, as in previous systems,10 that H-bonding from
-COOH, followed by H-bonding from -CH2OH groups, in
that order favors the aggegation of a monodendron in a
supramolecular dendrimer. In addition, monodendrons 12Gn-
AG-CH3 which do not have a H-bonding source, self-assemble
into spherical dendrimers of lower stability. This demonstates
that van der Waals interactions between the CH2 groups and
those between the aromatic groups can be solely responsible
for this self-assembly process. Therefore, they must also have
an important contribution in the case of the self-assembly of
12Gn-AG-CH2OH and 12Gn-AG. Previously, only van der
Waals interactions induced by fluorophobic effect were shown
to solely be able to aggregate a supramolecular dendrimer.10h
More details on these and other systems which self assemble
Via van der Waals interactions and on the assembly mechanism
will be published elsewhere.
and supramolecular systems43 with more complex architectures
and their potential technological applications will be addressed
in future publications.
Experimental Section
Materials. LiAlH4 (95+%), SOCl2 (99+%), 2,6-di-tert-butylpyri-
dine (97%), methyl 3,4,5-trihydroxybenzoate (98%), and anhydrous K2-
CO3 (all from Aldrich) were used as received. NMP, DMF and CH2Cl2
(all ACS reagent from Fisher) were dried over CaH2 and distilled. Et2O
(Fisher) was refluxed over sodium benzophenone ketyl and distilled
freshly before use.
General Methods. 1H NMR (200 MHz), 19F NMR (188 MHz),
and 13C NMR (50 MHz) spectra were recorded on a Varian Gemini
200 spectrometer. The purity of products was determined by a
combination of TLC on silica gel plates (Kodak) with fluorescent
indicator, NMR spectroscopy, elemental analysis, matrix assisted laser
desorption ionization time-of-flight (MALDI-TOF) mass spectrometry,
GPC, and HPLC. MALDI-TOF was performed on a Finnigan Vision
2000 TOF mass spectrometer with 3,5-dihydroxybenzoic acid matrix.
A Perkin-Elmer Series 10 HPLC equipped with an LC-100 column
oven, Nelson Analytical 900 Series integrator data station, and two
Perkin-Elmer PL gel columns of 5 × 102 and 1 × 104 Å was used in
both HPLC and GPC mode. THF was used as solvent at the oven
temperature of 40 °C unless otherwise noted. Detection was by UV
absorbance at 254 nm. Polystyrene standards (1.02 e Mw/Mn e 1.13)
were used to construct the calibration curve. Thermal transitions were
measured on a Perkin Elmer DSC-7. Zn and In were used as calibration
standards. In all cases, the heating and cooling rates were 10 °C min-1
unless otherwise noted. First order transition temperatures were
reported as the maxima and minima of their endothermic and
exothermic peaks. Glass transition temperatures (Tg) were read at the
middle of the change in heat capacity. Small-angle diffraction (SAXD)
from powder specimens was recorded with a quadrant detector at Station
8.2 of the Synchotron Radiation Source at Daresbury, UK. Small and
wide-angle diffraction from monodomain samples was recorded with
an image plate area detector (MarResearch) using graphite-monochro-
matized CuKR radiation. In both cases samples in capillaries were
held in a custom-built temperature cell controlled to within (0.1 °C.
The beampath up to the beamstop was either evacuated or flushed with
N2.
Synthesis. The synthesis and characterization of methyl 3,4,5-tris-
(n-dodecan-1-yloxy)benzoate (12G1-AG-CH3) and 3,4,5-tris(n-dode-
can-1-yloxy)benzoic acid (12G1-AG) were described previously.10a,d
General Procedure for the Synthesis of 12Gn-AG-CH2OH.
Synthesis of 3,4,5-Tris(n-dodecan-1-yloxy)benzyl Alcohol (12G1-
AG-CH2OH). 12G1-AG-CH2OH was obtained by the reduction of
12G1-AG with LiAlH4. To a suspension of 2.17 g (55.5 mmol) of
LiAlH4 in 50 mL of anhydrous Et2O 12G1-AG-CH3 was added
dropwise and the mixture was stirred for 1 h at room temperature under
N2 after which time TLC and 1H NMR analyses (δ 7.25, δ 3.89
disappeared) indicated complete conversion. The reaction was quenched
by dropwise, addition of 2 mL of H2O, 2 mL of 15% NaOH, and 6
mL of H2O. The granular salts were filtered and rinsed with THF.
Evaporation of the solvent afforded a white solid which upon
recrystallization from acetone at 4 °C yielded 45.7 g (93.4%) of a white
powder. Thermal transitions are recorded in Table 1. Purity (HPLC),
99+%; TLC (hexanes:ethyl acetate, 5:1): Rf ) 0.21. 1H NMR (CDCl3,
TMS, δ, ppm): 0.88 (t, 9H, CH3(CH2)11, J ) 6.1 Hz), 1.26 (overlapped
peaks, 48H, CH3(CH2)8), 1.45 (m, 6H, CH3(CH2)8CH2), 1.80 (m, 6H,
CH2CH2OAr), 3.94 (t, 2H, CH2OAr, 4 position, J ) 6.8 Hz), 3.97 (t,
4H, CH2OAr, 3,5 positions, J ) 7.0 Hz), 4.59 (d, 2H, CH2OH), 6.56
(s, 2H, ortho to CH2OH); 13C NMR (CDCl3, δ, ppm): 14.0 (CH3),
22.6 (CH3CH2), 26.1 (CH2CH2CH2OAr), 29.4 (CH3(CH2)2CH2), 29.6
(CH3(CH2)3(CH2)5), 30.3 (CH2CH2OAr), 31.9 (CH3CH2CH2), 65.4
(CH2OH), 69.0 (CH2OAr, 3,5 positions), 73.4 (CH2OAr, 4 position),
105.1 (ortho to CH2OH), 136.2 (para to CH2OH), 137.5 (ipso to CH2),
153.1 (meta to CH2OH).
Conclusions
The cone-shaped monodendrons 12Gn-AG with n ) 2, 3
and the hemispherical one with n ) 4 form a novel thermotropic
LC cubic phase with symmetry Pm3hn. Studies of electron
density profiles and histograms computed from the X-ray
diffraction data demonstrate based on a micellar like model that
self-assembled supramolecular dendrimers with the aromatic
1
regions centered around the corners, body-center, and the /4
3
and /4 positions along one of the bisectors of each face are
formed. This model is quite similar to that accepted for the
lyotropic phase with the same symmetry. All supramolecular
dendrimers can be well approximated by a spherical shape.
However, those which lie on face bisectors are in fact highly
rounded tetrahedra. The averaged shape of a monodendron is
conical or wedge-like in the case of 12G2-AG and 12G3-AG
and hemispherical in 12G4-AG. The solid angle subtended at
the micellar center by a peripheral alkoxy chain cross-section
decreases with increasing monodendron generation. This leads
to an increase in the size of micelles and of the entire unit cell
as one moves from 12G2-AG to 12G4-AG.
Comparatively fine structural detail obtained helps elucidate
certain features regulating the stability of the cubic mesophase.
For example, from the position and depth of density minima it
is predicted and experimentally demonstrated that the Pm3hn
phase does not form in the first generation monodendron 12G1-
AG and may not form in the second generation monodendrons
containing shorter alkyl chains. Further isomorphous replace-
ment studies of this type of monodendron molecules having
partially fluorinated alkyl regions and of their salts with heavy
metals are under way. The present is the first example of the
rational design of monodendrons which self-assemble into
supramolecular spherical dendrimers and the first quantitative
structural characterization of their shape, size, and structure with
the aid of a novel thermotropic cubic LC phase. These
conclusive structural experiments were possible, because the
liquid-like short-range interactions of the cubic phase provided
the long-range periodicity necessary for detailed electron
mapping by X-ray diffraction. The use of this novel shape of
thermotropic soft order42 in the design of new macromolecular
Synthesis of 3,4,5-Tris(n-dodecan-1-yloxy)benzyl Chloride (12G1-
AG-CH2Cl). 12G1-AG-CH2Cl was prepared by chlorination of 12G1-
(43) Lehn, J. M. Supramolecular Chemistry, VCH: Weinheim, 1995.
(44) Nystrom, R. F.; Brown, W. G. J. Am. Chem. Soc. 1947, 69, 1197.
(42) deGennes, P.-G. Angew. Chem., Int. Ed. Engl. 1992, 31, 842.

Spherical Supramolecular Dendrimers
J. Am. Chem. Soc., Vol. 119, No. 7, 1997 1553
AG-CH2OH with SOCl2. To a solution of 45.7 g (69.1 mmol) of
12G1-AG-CH2OH in 460 mL of dry CH2Cl2, a catalytic amount (1
mL) of DMF, followed by 11.5 g (96.8 mmol) of SOCl2 (dropwise)
was added with stirring. Approximately 30 min after the addition of
SOCl2 the reaction was complete (TLC, Rf ) 0.5; 20:1 hexanes:ethyl
acetate). The solvent and excess SOCl2 were distilled under vacuum.
The resulting white solid was dissolved in Et2O, washed three times
with H2O, dried over MgSO4, and filtered, and the solvent was
rotoevaporated. After vacuum drying for 1 h, 42.8 g (91.1%) of white
powder was obtained, mp 47-47.5 °C. Purity (HPLC), 99+%. 1H
NMR (CDCl3, TMS, δ, ppm): 0.89 (t, 9H, CH3(CH2)11, J ) 6.2 Hz),
1.28 (overlapped peaks, 48H, CH3(CH2)8), 1.47 (m, 6H, CH3(CH2)8CH2),
1.77 (m, 6H, CH2CH2OAr), 3.95 (t, 2H, CH2OAr, 4 position, J ) 6.5
Hz), 3.98 (t, 4H, CH2OAr, 3,5 positions, J ) 6.4 Hz), 4.51 (s, 2H,
CH2Cl), 6.58 (s, 2H, ortho to CH2Cl); 13C NMR (CDCl3, δ, ppm):
14.1 (CH3), 22.7 (CH3CH2), 26.1 (CH2CH2CH2OAr), 29.4 (CH3-
(CH2)2CH2), 29.6 (CH3(CH2)3(CH2)5), 30.3 (CH2CH2OAr), 31.9 (CH3-
CH2CH2), 46.9 (CH2Cl), 69.1 (CH2OAr, 3,5 positions), 73.4 (CH2OAr,
4 position), 107.0 (ortho to CH2Cl), 132.3 (para to CH2Cl), 138.3 (ipso
to CH2), 153.2 (meta to CH2Cl).
to CH2, 3,4,5 positions), 153.0 (meta to CH2, 4 position, meta to CH2-
OH), 153.2 (meta to CH2, 3,5 positions). Anal Calcd for C136H242O13:
C, 78.33; H, 11.70. Found: C, 78.16; H, 11.66.
General Procedure for the Synthesis of 12Gn-AG-CH2Cl (n >
1). 3,4,5-Tris[3′,4′,5′-tris(n-dodecan-1-yloxy)benzyloxy)]benzyl Chlo-
ride (12G2-AG-CH2Cl). 12G2-AG-CH2OH (6.0 g, 2.9 mmol) was
dissolved in 60 mL of dry CH2Cl2. 2,6-Di-tert-butylpyridine (1.5 g,
8.1 mmol), DMF (several drops), and SOCl2 (0.48 g, 4.1 mmol) were
added dropwise. After complete addition, the reaction was monitored
by 1H NMR. Within few minutes, a complete conversion was observed.
The product was freeze-dried from benzene solution to obtain a white
powder which was used immediately in the next step without further
purification. A sample free of 2,6-di-tert-butylpyridine was obtained
for analytical purposes by precipitation from CH2Cl2 into acetone. TLC
(20:1 hexanes:ethyl acetate): Rf ) 0.5. 1H NMR (CDCl3, δ, ppm,
TMS): 0.88 (t, 27H, CH3(CH2)11, J ) 6.0 Hz), 1.26-1.41 (overlapped
peaks, 162H, CH3(CH2)8), 1.74 (m, 18H, CH2CH2OAr), 3.76 (t, 4H,
CH2OAr, 4-(3′,5′) position, J ) 5.9 Hz), 3.88 (t, 8H, 3,5-(3′,5′)
positions, J ) 6.3 Hz), 3.91 (t, 6H, CH2OAr, 3,4,5-(4′) positions, J )
6.3 Hz), 4.47 (s, 2H, CH2Cl), 4.96 (s, 2H, ArCH2OAr, 4 position),
4.99 (s, 4H, ArCH2OAr, 3,5 positions), 6.60 (s, 4H, ortho to CH2, 3,5
positions), 6.67 (s, 2H, ortho to CH2, 4 position), 7.26 (s, 2H, ortho to
CH2Cl). 13C NMR (CDCl3, δ, ppm, TMS): 14.1 (CH3), 22.7 (CH3CH2),
26.2 (CH2CH2CH2OAr), 29.4 (CH3(CH2)2CH2), 29.7 (CH3(CH2)3(CH2)5),
30.4 (CH2CH2OAr), 31.9 (CH3CH2CH2), 46.6 (CH2Cl), 69.0 (CH2CH2-
OAr, 3,4,5-(3′,5′) positions), 71.7 (ArCH2OAr, 3,5 positions), 73.3
(CH2CH2OAr, 3,4,5-(4′) positions), 75.2 (ArCH2OAr, 4 position), 105.6
(ortho to CH2, 3,5 positions), 106.2 (ortho to CH2, 4 position), 108.8
(ortho to CH2Cl), 131.9 (para to CH2, 3,5 positions), 132.6 (para to
CH2, 4 position), 132.9 (para to CH2Cl), 137.8 (ipso to CH2, 3,4,5
positions), 138.6 (ipso to CH2Cl), 153.0 (meta to CH2, 4 position, meta
to CH2Cl), 153.2 (meta to CH2, 3,5 positions).
Methyl 3,4,5-Tris[3′,4′,5′-tris(n-dodecan-1-yloxy)benzyloxy)]ben-
zoate (12G2-AG-CH3). 12G2-AG-CH3 was obtained by the alkylation
of methyl 3,4,5-trihydroxybenzoate with 12G1-AG-CH2Cl. A mixture
of K2CO3 (23.1 g, 0.167 mmol) in 280 mL of dry DMF was purged
for 1 h with N2. Methyl 3,4,5-trihydroxybenzoate (3.43 g, 18.6 mmol)
was added, and the mixture was heated to 65 °C. A solution of 12G1-
AG-CH2Cl (38.0 g, 55.9 mmol) in 220 mL of DMF was added rapidly.
After 1.5 h, the conversion was 91% (1H NMR analysis). No side
products were detected. After 3.5 h, the completed reaction mixture
was poured into ice-H2O. The precipitated product was filtered and
recrystallized from a mixture of CH2Cl2 and MeOH to obtain a light
tan powder. Further purification by column chromatography (b. Al2O3;
CH2Cl2) yielded 34.6 g (88.0%) of a white powder. Purity (GPC),
99+%; TLC (20:1 hexanes:ethyl acetate), Rf ) 0.20. 1H NMR (CDCl3,
δ, ppm, TMS): 0.88 (t, 27H, CH3(CH2)11, J ) 6.4 Hz), 1.26-1.43
(overlapped peaks, 162H, CH3(CH2)8), 1.71 (m, 18H, CH2CH2OAr),
3.75 (t, 4H, CH2OAr, 4-(3′,5′) position, J ) 6.4 Hz), 3.88 (t, 8H, 3,5-
(3′,5′) positions, J ) 6.4 Hz), 3.88 (s, 3H, CO2CH3), 3.93 (t, 6H, CH2-
OAr, 3,4,5-(4′) positions, J ) 6.5 Hz), 5.03 (s, 6H, ArCH2OAr), 6.60
(s, 2H, ortho to CH2, 4′ position), 6.63 (s, 4H, ortho to CH2, 3′,5′
position), 7.38 (s, 2H, ortho to CO2CH3). 13C NMR (CDCl3, δ, ppm,
TMS): 14.1 (CH3), 22.7 (CH3CH2), 26.2 (CH2CH2CH2OAr), 29.4 (CH3-
(CH2)2CH2), 29.7 (CH3(CH2)3(CH2)5), 30.4 (CH2CH2OAr), 31.9 (CH3-
CH2CH2), 52.2 (CO2CH3), 69.1 (CH2CH2OAr, 3,4,5-(3′,5′) positions),
71.7 (ArCH2OAr, 3,5 positions), 73.4 (CH2CH2OAr, 3,4,5-(4′) posi-
tions), 75.1 (ArCH2OAr, 4 position), 105.7 (ortho to CH2, 3,5 positions),
106.2 (ortho to CH2, 4 position), 109.6 (ortho to CO2CH3), 125.1 (ipso
to CO2CH3), 131.7 (para to CH2, 3,5 position), 132.4 (para to CH2, 4
position), 137.8 (ipso to CH2, 3,4,5 position), 142.1 (para to CO2CH3),
152.5 (meta to CO2CH3), 153.0 (meta to CH2, 4 position), 153.3 (meta
to CH2, 3,5 position), 166.5 (CO2CH3). Anal Calcd for C137H242O14:
C, 77.86; H, 11.54. Found: C, 77.93; H, 11.64.
Methyl 3,4,5-Tris{3′,4′,5′-tris[3′′,4′′,5′′-tris(n-dodecan-1-yloxy-
benzyloxy)benzyloxy]benzyloxy}benzoate (12G3-AG-CH3). A mix-
ture of K2CO3 (3.29 g, 23.9 mmol) and 230 mL of dry NMP was purged
for 0.5 h with N2. Methyl 3,4,5-trihydroxybenzoate (0.489 g, 2.65
mmol) was added, and the mixture was heated to 90 °C. A slurry of
12G2-AG-CH2Cl (16.7 g, 7.96 mmol) in 100 mL of warm NMP was
1
added rapidly. After 2 h, a 92% conversion was determined by H
NMR. No side products were detected. After 4 h, the completed hot
reaction mixture was poured into 1.5 L of ice-H2O, and the precipitated
solid was filtered. The moist solid was dissolved in Et2O, washed with
H2O, and dried over MgSO4. Purification by column chromatography
(b. Al2O3, hexanes) yielded 12.3 g (72.7%) of a light brown, glassy
material. Purity (GPC), 99+%; TLC (10:1 hexanes:ethyl acetate): Rf
) 0.5. 1H NMR (CDCl3, δ, ppm, TMS): 0.88 (t, 81H, CH3(CH2)11, J
) 6.0 Hz), 1.26-1.41 (overlapped peaks, 486H, CH3(CH2)8), 1.71 (m,
54H, CH2CH2OAr), 3.66-3.91 (overlapped peaks, 57H, CH2CH2OAr,
CO2CH3), 4.77 (bs, 4H, ArCH2OAr, 4-(3′,5′) position), 4.81 (bs, 2H,
ArCH2OAr, 4-(4′) position), 4.91 (bs, 12H, ArCH2OAr, 3,5-(3′,4′,5′)
positions), 5.05 (bs, 4H, ArCH2OAr, 3,5 positions), 5.12 (bs, 2H,
ArCH2OAr, 4 position), 6.51 (s, 6H, ortho to CH2, 4-(3′,4′,5′) position),
6.57 (s, 12H, ortho to CH2, 3,5-(3′,4′,5′) positions), 6.80 (s, 4H, ortho
to CH2, 3,5 positions), 6.85 (s, 2H, ortho to CH2, 4 position), 7.38 (s,
2H, ortho to CO2CH3). 13C NMR (CDCl3, δ, ppm, TMS): 14.1 (CH3),
22.7 (CH3CH2), 26.2 (CH2CH2CH2OAr), 29.4 (CH3(CH2)2CH2), 29.8
(CH3(CH2)3(CH2)5), 30.5 (CH2CH2OAr), 31.9 (CH3CH2CH2), 52.2
(CO2CH3), 68.8, 68.9 (CH2CH2OAr, 3,4,5-[3′,4′,5′-(3′′,5′′)] positions),
71.4, 71.6 (ArCH2OAr, 3,5 positions and 3,4,5-(3′,5′) positions), 73.3
(CH2CH2OAr, 3,4,5-[3′,4′,5′-(4′′)] positions), 75.1 (ArCH2OAr, 4
position and 3,4,5-(4′) positions), 105.5 (ortho to CH2, 3,4,5-(3′,5′)
positions), 105.9 (ortho to CH2, 3,4,5-(4′) positions), 107.2 (ortho to
CH2, 3,5 positions), 108.0 (ortho to CH2, 4 position), 109.6 (ortho to
CO2CH3), 125.4 (ipso to CO2CH3), 131.8 (para to CH2, 3,4,5-(3′,5′)
positions), 132.3 (para to CH2, 3,5 positions), 132.7 (para to CH2, 3,4,5-
(4′) positions), 133.1 (para to CH2, 4 position), 137.7 (ipso to CH2,
3,4,5-(3′,4′,5′) positions), 138.3 (ipso to CH2, 3,4,5 positions), 142.2
(para to CO2CH3), 152.4 (meta to CO2CH3, meta to CH2, 4 position),
152.8 (meta to CH2, 3,5 positions), 153.0 (meta to CH2, 3,4,5-(4′)
positions), 153.2 (meta to CH2, 3,4,5-(3′,5′) positions), 166.3 (CO2-
CH3). Anal Calcd for C416H728O41: C, 78.24; H, 11.49. Found: C,
78.31; H, 11.29.
3,4,5-Tris[3′,4′,5′-tris(n-dodecan-1-yloxy)benzyloxy)]benzyl Al-
cohol (12G2-AG-CH2OH). From 12G2-AG-CH3 (8.00 g, 3.79 mmol)
and LiAlH4 (0.15 g, 35 mmol) were obtained 7.3 g (91.%) of a white
solid (after recrystallization from acetone). Purity (GPC), 99+%; TLC
(CH2Cl2): Rf ) 0.3. 1H NMR (CDCl3, δ, ppm, TMS): 0.88 (t, 27H,
CH3(CH2)11, J ) 6.4 Hz), 1.26-1.43 (overlapped peaks, 162H,
CH3(CH2)8), 1.70 (m, 18H, CH2CH2OAr), 3.77 (t, 4H, CH2OAr, 4-(3′,5′)
position, J ) 6.4 Hz), 3.88 (t, 8H, 3,5-(3′,5′) positions, J ) 6.4 Hz),
3.92 (t, 6H, CH2OAr, 3,4,5-(4′) positions, J ) 6.5 Hz), 4.56 (d, 2H,
CH2OH, J ) 6.02 Hz), 4.97 (s, 2H, ArCH2OAr, 4 position), 5.01 (s,
4H, ArCH2OAr, 3,5 positions), 6.62 (s, 4H, ortho to CH2, 3,5 positions),
6.63 (s, 2H, ortho to CH2OH), 6.67 (s, 2H, ortho to CH2, 4 position).
13C NMR (CDCl3, δ, ppm, TMS): 14.1 (CH3), 22.7 (CH3CH2), 26.2
(CH2CH2CH2OAr), 29.4 (CH3(CH2)2CH2), 29.5, 29.7 (CH3(CH2)3(CH2)5),
30.4 (CH2CH2OAr), 31.9 (CH3CH2CH2), 65.2 (CH2OH), 69.0 (CH2CH2-
OAr, 3,4,5-(3′,5′) positions), 71.5 (ArCH2OAr, 3,5 positions), 73.3
(CH2CH2OAr, 3,4,5-(4′) positions), 75.2 (ArCH2OAr, 4 position), 105.5
(ortho to CH2, 3,5 position), 106.2 (ortho to CH2, 4 position), 106.8
(ortho to CH2OH), 132.1 (para to CH2, 3,5 positions), 132.8 (para to
CH2, 4 position, para to CH2OH), 136.7 (ipso to CH2OH), 137.6 (ipso

1554 J. Am. Chem. Soc., Vol. 119, No. 7, 1997
Balagurusamy et al.
3,4,5-Tris{3′,4′,5′-tris[3′′,4′′,5′′-tris(n-dodecan-1-yloxybenzyloxy)-
benzyloxy]benzyloxy}benzyl Alcohol (12G3-AG-CH2OH). From
12G3-AG-CH3 (7.0 g, 1.1 mmol) and LiAlH4 (0.083 g, 2.2 mmol)
was obtained 5.4 g (77%) of a glassy, white solid after purification by
column chromatography (b. Al2O3; hexanes). Purity (GPC), 99+%.
1H NMR (CDCl3, δ, ppm, TMS): 0.88 (t, 81H, CH3(CH2)11, J ) 6.0
Hz), 1.26-1.44 (overlapped peaks, 486H, CH3(CH2)8), 1.69 (m, 54H,
CH2CH2OAr), 3.66-3.92 (overlapped peaks, 54H, CH2CH2OAr), 4.44
(d, 2H, CH2OH, J ) 6.5 Hz), 4.83 (bs, 4H, ArCH2OAr, 4-(3′,5′)
position), 4.85 (bs, 2H, ArCH2OAr, 4-(4′) position), 4.93 (bs, 12H,
ArCH2OAr, 3,5-(3′,4′,5′) position), 4.98 (bs, 4H, ArCH2OAr, 3,5
positions), 5.05 (bs, 2H, ArCH2OAr, 4 position), 6.47 (s, 2H, ortho to
CH2OH), 6.52 (s, 6H, ortho to CH2, 4-(3′,4′,5′) position), 6.56 (s, 8H,
ortho to CH2, 3,5-(3′,5′) positions), 6.60 (s, 4H, ortho to CH, 3,5-(4′)
position), 6.73 (s, 4H, ortho to CH2, 3,5 positions), 6.86 (s, 2H, ortho
to CH2, 4 position). 13C NMR (CDCl3, δ, ppm, TMS): 14.1 (CH3),
22.7 (CH3CH2), 26.2 (CH2CH2CH2OAr), 29.4 (CH3(CH2)2CH2), 29.8
(CH3(CH2)3(CH2)5), 30.4 (CH2CH2OAr), 31.9 (CH3CH2CH2), 64.7
(CH2OH), 68.0, 68.9 (CH2CH2OAr, 3,4,5-[3′,4′,5′-(3′′,5′′)] positions),
71.4 (ArCH2OAr, 3,5 position and 3,4,5-(3′,5′) positions), 73.3
(CH2CH2OAr, 3,4,5-[3′,4′,5′-(4′′)] positions), 75.2 (ArCH2OAr, 4
position and 3,4,5-(4′) positions), 105.4 (ortho to CH2, 3,4,5-(3′,5′)
positions), 106.0 (ortho to CH2, 3,4,5-(4′) position), 106.6 (ortho to
CH2OH, ortho to CH2, 3,5 positions), 108.3 (ortho to CH2, 4 position),
132.0 (para to CH2, 3,4,5-(3′,5′) positions), 132.8 (para to CH2, 3,4,5-
(4′) positions), 133.1 (para to CH2, 3,5 positions), 133.6 (para to CH2,
4 position), 136.9 (ipso to CH2OH), 137.6 (ipso to CH2, 3,4,5-(3′,4′,5′)
positions), 137.9 (ipso to CH2, 3,5 position), 138.2 (ipso to CH2, 4
position), 152.6 (meta to CH2OH, meta to CH2, 4 position), 152.7 (meta
to CH2, 3,5 positions), 153.0 (meta to CH2, 3,4,5-(4′) positions), 153.2
(meta to CH2, 3,4,5-(3′,5′) positions).
room temperature, EtOH was decanted, and the solid residue was
dissolved in THF. The solution was neutralized with of 50% aqueous
acetic acid. THF was added periodically to maintain a homogeneous
solution. After acidification, the product was precipitated in acetone
and collected by vacuum filtration. A white powder (0.88g, 88%) was
obtained. Purity (GPC), 99+%; TLC (20:1 CHCl3:MeOH), Rf ) 0.33.
1H NMR (CDCl3, δ, ppm, TMS): 0.88 (t, 27H, CH3(CH2)11, J ) 6.4
Hz), 1.26-1.42 (overlapped peaks, 162H, CH3(CH2)8), 1.71 (m, 18H,
CH2CH2OAr), 3.75 (t, 4H, CH2OAr, 4-(3′,5′) position, J ) 6.4 Hz),
3.89 (t, 8H, 3,5-(3′,5′) positions, J ) 6.4 Hz), 3.93 (t, 6H, CH2OAr,
3,4,5-(4′) positions, J ) 6.5 Hz), 5.04 (s, 6H, ArCH2OAr), 6.60 (s,
2H, ortho to CH2, 4 position), 6.64 (s, 4H, ortho to CH2, 3,5 positions),
7.45 (s, 2H, ortho to CO2H). 13C NMR (CDCl3, δ, ppm, TMS): 14.1
(CH3), 22.7 (CH3CH2), 26.2 (CH2CH2CH2OAr), 29.4 (CH3(CH2)2CH2),
29.7 (CH3(CH2)3(CH2)5), 30.4 (CH2CH2OAr), 31.9 (CH3CH2CH2), 69.1
(CH2CH2OAr, 3,4,5-(3′,5′) positions), 71.7 (ArCH2OAr, 3,5 positions),
73.4 (CH2CH2OAr, 3,4,5-(4′) positions), 75.2 (ArCH2OAr, 4 position),
105.8 (ortho to CH2, 3,5 positions), 106.2 (ortho to CH2, 4 position),
110.1 (ortho to CO2H), 124.2 (ipso to CO2H), 131.5 (para to CH2, 3,5
positions), 132.3 (para to CH2, 4 position), 137.9 (ipso to CH2, 3,4,5
positions), 143.4 (para to CO2H), 152.6 (meta to CO2H), 153.0 (meta
to CH2, 4 position), 153.3 (meta to CH2, 3,5 positions), 171.5 (CO2H).
Anal Calcd for C136H240O14: C, 77.81; H, 11.52. Found: C, 78.03; H,
11.31.
3,4,5-Tris{3′,4′,5′-tris[3′′,4′′,5′′-tris(n-dodecan-1-yloxybenzyloxy)-
benzyloxy]benzyloxy}benzoic Acid (12G3-AG). From 12G3-AG-
CH3 (1.00 g, 0.157 mmol) was obtained 0.40 g (40%) of a white
powder. Purity (GPC), 99+%; TLC (20:1 CHCl3:MeOH), Rf ) 0.68.
1H NMR (CDCl3, δ, ppm, TMS): 0.88 (t, 81H, CH3(CH2)11, J ) 6.0
Hz), 1.25 (overlapped peaks, 486H, CH3(CH2)8), 1.68 (m, 54H, CH2-
CH2OAr), 3.69-3.89 (overlapped peaks, 54H, CH2CH2OAr), 4.81 (bs,
4H, ArCH2OAr, 4-(3′,5′) position), 4.83 (bs, 2H, ArCH2OAr, 4-(4′)
position), 4.91 (bs, 12H, ArCH2OAr, 3,5-(3′,4′,5′) positions), 5.05 (bs,
4H, ArCH2OAr, 3,5 positions), 5.12 (bs, 2H, ArCH2OAr, 4 position),
6.52 (s, 4H, ortho to CH2, 4-(3′,5′) position), 6.54 (s, 2H, ortho to
CH2, 4-(4′) position), 6.57 (s, 12H, ortho to CH2, 3,5-(3′,4′,5′) positions),
6.75 (s, 4H, ortho to CH2, 3,5 positions), 6.87 (s, 2H, ortho to CH2, 4
position). 13C NMR (CDCl3, δ, ppm, TMS): 14.1 (CH3), 22.7
(CH3CH2), 26.2 (CH2CH2CH2OAr), 29.4 (CH3(CH2)2CH2), 29.8 (CH3-
(CH2)3(CH2)5), 30.5 (CH2CH2OAr), 32.0 (CH3CH2CH2), 68.8, 68.9
(CH2CH2OAr, 3,4,5-[3′,4′,5′-(3′′,5′′)] positions), 71.6 (ArCH2OAr, 3,5
position and 3,4,5-(3′,5′) positions), 73.2 (CH2CH2OAr, 3,4,5-[3′,4′,5′-
(4′′)] positions), 75.1 (ArCH2OAr, 4 and 3,4,5-(4′) positions), 105.6
(ortho to CH2, 3,4,5-(3′,5′) positions), 105.8 (ortho to CH2, 3,4,5-(4′)
positions), 107.2 (ortho to CH2, 3,5 positions), 107.8 (ortho to CH2, 4
position), 110.0 (ortho to CO2H), 124.6 (ipso to CO2H), 131.8 (para
to CH2, 3,4,5-(3′,5′) positions), 132.2 (para to CH2, 3,5 positions), 132.7
(para to CH2, 3,4,5-(4′) positions), 133.1 (para to CH2, 4 position),
137.6, 137.7 (ipso to CH2, 3,4,5-(3′,4′,5′) positions), 138.3 (ipso to CH2,
3,4,5 positions), 143.0 (para to CO2H), 152.5 (meta to CH2, 4 position),
153.0 (meta to CH2, 3,5 position), 153.2 (meta to CH2, 3,4,5-(3′,4′,5′)
positions), 169.8 (CO2H). Anal Calcd for C415H726O41: C, 78.22; H,
11.48. Found: C, 78.01; H, 11.30.
3,4,5-Tris{3′,4′,5′-tris[3′′,4′′,5′′-tris(n-dodecan-1-yloxybenzyloxy)-
benzyloxy]benzyloxy}benzyl Chloride (12G3-AG-CH2Cl). From
12G3-AG-CH2OH (0.90 g, 0.14 mmol), 2,6-di-tert-butylpyridine (78
mg, 0.40 mmol), and SOCl2 (20 mg, 0.17 mmol) was obtained 0.90 g
(100%) of a light yellow, glassy solid which was used without further
purification. Complete conversion to the benzyl chloride (s, 2H, 4.45
ppm) and the absence of side reactions was verified by 1H NMR
analysis of the reaction mixture.
Methyl 3,4,5-Tris(3′,4′,5′-tris{3′′,4′′,5′′-tris[3′′′,4′′′,5′′′-tris(n-dode-
can-1-yloxybenzyloxy)benzyloxy]benzyloxy}benzyloxy)benzoate
(12G4-AG-CH3). 12G4-AG-CH3 was synthesized by the same general
procedure described for the synthesis of 12G3-AG-CH3 except that
the reaction temperature was 80 °C. From K2CO3 (1.4 g, 10 mmol),
methyl 3,4,5-trihydroxybenzoate (30.8 mg, 0.167 mmol), and 12G3-
AG-CH2Cl (3.20 g, 0.502 mmol) in 32 mL of NMP (80 °C, 20 h) was
obtained 1.60 g (50.0%) of a light brown, glassy solid after purification
by column chromatography (b. Al2O3; hexanes). Purity (GPC), 99+%;
TLC (hexanes), Rf ) 0.9. 1H NMR (CDCl3, δ, ppm, TMS): 0.88 (broad
peak, 243H, CH3(CH2)11), 1.26 (broad peak, 1458H, CH3(CH2)8), 1.71
(broad peak, 162H, CH2CH2OAr), 3.64-3.79 (broad peaks, 165H,
CH2CH2OAr, CO2CH3), 4.76 (broad peak, 78H, ArCH2OAr), 6.50
(broad peak, 54H, ortho to CH2, 3,4,5-[3′,4′,5′-(3′′,4′′,5′′)] positions),
6.81 (broad peak, 24H, ortho to CH2, 3,4,5-(3′,4′,5′) and 3,4,5 positions).
13C NMR (CDCl3, δ, ppm, TMS): 14.1 (CH3), 22.7 (CH3CH2), 26.2
(CH2CH2CH2OAr), 29.4 (CH3(CH2)2CH2), 29.8 (CH3(CH2)3(CH2)5 and
CH2CH2OAr, 3,5 positions), 30.5 (CH2CH2OAr, 4 position), 31.9 (CH3-
CH2CH2), 52.2 (CO2CH3), 68.8 (CH2CH2OAr, 3,5 positions), 71.5
(ArCH2OAr, 3,5 positions), 73.2 (CH2CH2OAr, 4 positions), 74.9
(ArCH2OAr, 4 positions), 105.5 (ortho to CH2, 3,4,5-[3′,4′,5′-(3′′,4′′,5′′)]
positions), 107.2 (ortho to CH2, 3,4,5-(3′,4′,5′) and 3,4,5 positions),
130.3 (ipso to CO2CH3), 131.7 (para to CH2, 3,4,5-[3′,4′,5′-(3′′,4′′,5′′)]
positions), 132.7 (para to CH2, 3,4,5-(3′,4′,5′) position), 133.8 (para
to CH2, 3,4,5 positions), 137.7 (ipso to CH2, 3,4,5-[3′,4′,5′-(3′′,4′′,5′′)]
positions), 138.2 (ipso to CH2, 3,4,5-(3′,4′,5′) and 3,4,5 positions),
151.7 (meta to CO2CH3), 153.1 (meta to CH2). Anal Calcd for
3,4,5-Tris(3′,4′,5′-tris{3′′,4′′,5′′-tris[3′′′,4′′′,5′′′-tris(n-dodecan-1-
yloxybenzyloxy)benzyloxy]benzyloxy}benzyloxy)benzoic Acid (12G4-
AG). Hydrolysis of 12G4-AG-CH3 (1.4 g, 0.073 mmol) yielded 1.2
g (86%) of 12G4-AG1 after precipitation in acetone and subsequent
purification by column chromatography (b. Al2O3; hexanes). Purity
(GPC), 99+%; TLC (hexanes), Rf ) 0.9. 1H NMR (CDCl3, δ, ppm,
TMS): 0.88 (broad peak, 243H, CH3(CH2)11), 1.26 (broad peak, 1458H,
CH3(CH2)8), 1.61 (broad peak, 162H, CH2CH2OAr), 3.66-3.80 (broad
peaks, 162H, CH2CH2OAr), 4.78 (broad peak, 78H, ArCH2OAr), 6.50
(broad peak, 54H, ortho to CH2, 3,4,5-[3′,4′,5′-(3′′,4′′,5′′)] positions),
6.82 (broad peak, 24H, ortho to CH2, 3,4,5-(3′,4′,5′) and 3,4,5 positions).
13C NMR (CDCl3, δ, ppm, TMS): 14.0 (CH3), 22.7 (CH3CH2), 26.3
(CH2CH2CH2OAr), 29.4 (CH3(CH2)2CH2), 29.9 (CH3(CH2)3(CH2)5),
30.6 (CH2CH2OAr), 32.0 (CH3CH2CH2), 69.0 (CH2CH2OAr, 3,5
positions), 71.6 (ArCH2OAr, 3,5 positions), 73.2 (CH2CH2OAr, 4
positions), 74.9 (ArCH2OAr, 4 positions), 105.8 (ortho to CH2, 3,4,5-
[3′,4′,5′-(3′′,4′′,5′′)] positions), 107.3 (ortho to CH2, 3,4,5-(3′,4′,5′) and
3,4,5 positions), 131.8 (para to CH2, 3,4,5-[3′,4′,5′-(3′′,4′′,5′′)] posi-
tions), 132.8 (para to CH2, 3,4,5-(3′,4′,5′) positions), 133.8 (para to
C1253H728O122: C, 78.36; H, 11.47. Found: C, 78.31; H, 11.29.
General Procedure for the Basic Hydrolysis of 12Gn-AG-CH3
(n > 1). 3,4,5-Tris[3′,4′,5′-tris(n-dodecan-1-yloxy)benzyloxy)]ben-
zoic Acid (12G2-AG). 12G2-AG-CH3 (1.00 g, 0.473 mmol) was
suspended in a mixture of 95% EtOH (10 mL) and 10 N KOH (1 mL),
heated, and maintained at a gentle reflux for 3 h. After cooling to

Spherical Supramolecular Dendrimers
J. Am. Chem. Soc., Vol. 119, No. 7, 1997 1555
CH2, 3,4,5 positions), 137.8 (ipso to CH2, 3,4,5-[3′,4′,5′-(3′′,4′′,5′′)]
positions), 138.3 (ipso to CH2, 3,4,5-(3′,4′,5′) and 3,4,5 positions), 151.7
(meta to CO2H), 153.2 (meta to CH2), 169.5 (CO2H). Anal Calcd for
Research Department, DuPont, Wilmington, for providing the
preliminary data on MALDI-TOF MS.
C1252H2184O122: C, 78.36; H, 11.47. Found: C, 78.50; H, 11.40.
Supporting Information Available: Schematic drawing of
five cubic phases, MALDI-TOF spectra, NMR data and spectra,
DSC traces, powder and monodomain X-ray diffractograms,
electron density profiles, and histograms for 12G2-AG and their
discussion, and principles of phase formation by different
curvature (15 pages). See any current masthead page for
ordering and Internet access instructions.
Acknowledgment. The authors wish to acknowledge finan-
cial support from the National Science Foundation, U.S.A.
(DMR-92-06781), the Engineering and Physical Science Re-
search Council, UK, and the Synchrotron Radiation Source at
Daresbury, UK (for the beamtime and technical assistance). A
NATO traveling grant is also acknowledged. We are grateful
to Professor S. Z. D. Cheng of University of Akron for supplying
the mass density data and Dr. Charles McEwen of Central
JA963295I