Synthesis and retrostructural analysis of libraries of AB3 and constitutional isomeric AB2 phenylpropyl ether-based supramolecular dendrimers

Article abstract of DOI:10.1021/ja060062a

We report the synthesis of methyl esters of 3-(4-hydroxyphenyl)propionic, 3-(3,4-dihydroxyphenyl)propionic, 3-(3,5-dihydroxyphenyl)propionic, and 3-(3,4,5-trihydroxyphenyl)propionic acids and their use in a convergent iterative strategy to prepare up to four generations of three libraries, one of 3,4,5- and two of constitutional isomeric 3,4- and 3,5-substituted 3-phenylpropyl dendrons. Each library contains 3-[3,4,5-tris(dodecyl-1-oxy) phenyl]propyl-, 3-[3,4-bis(dodecyl-1-oxy)phenyl]propyl-, 3-{3,4-bis[3-(4- dodecyl-1-oxyphenyl)propyl-1-oxy]phenyl}propyl-, and 3-{3,4,5-tris[3-(4-dodecyl- 1-oxyphenyl)propyl-1-oxy]phenyl}propyl ether first-generation dendrons on their periphery and -CO₂CH₃, -COOH, and -CH₂OH groups at their apex. Regardless of their generation number and their periphery, internal, and apex structures, these dendrons self-assemble into supramolecular dendrimers that self-organize into all periodic and quasi-periodic assemblies encountered previously and in several unencountered with architecturally related benzyl ether-based supramolecular dendrimers. A variety of porous columnar lattices that were previously obtained only from dendritic dipeptides and hollow supramolecular spheres were also discovered from these building blocks. The more flexible and less compact 3-phenylpropyl ether repeat units are stable under acidic conditions, facilitate a simpler synthetic strategy, provide faster dynamics of self-assembly into higher-order supramolecular structures of larger dimensions, exhibit lower transition temperatures than the corresponding benzyl ether homologues, and demonstrate the generality of the self-assembly concept based on amphiphilic dendrons.

Full text of DOI:10.1021/ja060062a

Published on Web 02/15/2006
Synthesis and Retrostructural Analysis of Libraries of AB3
and Constitutional Isomeric AB2 Phenylpropyl Ether-Based
Supramolecular Dendrimers
Virgil Percec,*,† Mihai Peterca,‡ Monika J. Sienkowska,† Marc A. Ilies,†
Emad Aqad,† Jan Smidrkal,† and Paul A. Heiney‡
Contribution from the Roy & Diana Vagelos Laboratories, Department of Chemistry, UniVersity
of PennsylVania, Philadelphia, PennsylVania 19104-6323, and Department of Physics and
Astronomy, UniVersity of PennsylVania, Philadelphia, PennsylVania 19104-6396
Received January 4, 2006; E-mail: percec@sas.upenn.edu
Abstract: We report the synthesis of methyl esters of 3-(4-hydroxyphenyl)propionic, 3-(3,4-dihydroxyphenyl)-
propionic, 3-(3,5-dihydroxyphenyl)propionic, and 3-(3,4,5-trihydroxyphenyl)propionic acids and their use
in a convergent iterative strategy to prepare up to four generations of three libraries, one of 3,4,5- and two
of constitutional isomeric 3,4- and 3,5-substituted 3-phenylpropyl dendrons. Each library contains 3-[3,4,5-
tris(dodecyl-1-oxy)phenyl]propyl-, 3-[3,4-bis(dodecyl-1-oxy)phenyl]propyl-, 3-{3,4-bis[3-(4-dodecyl-1-ox-
yphenyl)propyl-1-oxy]phenyl}propyl-, and 3-{3,4,5-tris[3-(4-dodecyl-1-oxyphenyl)propyl-1-oxy]phenyl}propyl
ether first-generation dendrons on their periphery and -CO2CH3, -COOH, and -CH2OH groups at their
apex. Regardless of their generation number and their periphery, internal, and apex structures, these
dendrons self-assemble into supramolecular dendrimers that self-organize into all periodic and quasi-periodic
assemblies encountered previously and in several unencountered with architecturally related benzyl ether-
based supramolecular dendrimers. A variety of porous columnar lattices that were previously obtained
only from dendritic dipeptides and hollow supramolecular spheres were also discovered from these building
blocks. The more flexible and less compact 3-phenylpropyl ether repeat units are stable under acidic
conditions, facilitate a simpler synthetic strategy, provide faster dynamics of self-assembly into higher-
order supramolecular structures of larger dimensions, exhibit lower transition temperatures than the
corresponding benzyl ether homologues, and demonstrate the generality of the self-assembly concept based
on amphiphilic dendrons.
dronized with self-assembling dendrons.13,14 Several per-
iodic7d,10,11a,15 and quasi-periodic11b assemblies that were not
Introduction
Dendrimers and dendrons1 synthesized by divergent2 and
convergent3 iterative methods provide some of the most
powerful monodisperse architectural motifs currently explored
at the interface between chemistry, biology, physics, medicine,
and nanoscience.4 Self-assembling dendrons that provide su-
pramolecular dendrimers with the structural perfection that
allows self-organization in lattices5 are generated from dendrons
based on anisotropic mesogenic repeat units,6a-f,r mesogenic
dendrons, and dendrimers,6g,k from conventional dendrimers
functionalized with mesogenic groups on their periphery,6h,j from
amphiphilic dendrons based on benzyl ether units,7-11 and from
other amphiphilic dendrons,12 as well as from polymers den-
previously encountered in organic or biological molecules have
been discovered with the aid of self-assembling dendrons.
Benzyl ether-based self-assembling dendrons functionalized at
their apex are currently used to investigate the structural origin
of functions and to create functions, according to biological
principles, via their 3D tertiary and quatenary structures.15 Self-
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† Department of Chemistry.
‡ Department of Physics and Astronomy.
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3324
J. AM. CHEM. SOC. 2006, 128, 3324-3334
10.1021/ja060062a CCC: $33.50 © 2006 American Chemical Society

AB3 and AB2 Phenylpropyl Ether-Based Dendrimers
A R T I C L E S
assembling benzyl ether-based dendrons have limited stability
under acidic conditions,7d and therefore, their accelerated
synthesis requires the preparation of ABn (n ) 1-3) benzyl
chlorides from the corresponding benzyl alcohols and SOCl2
followed by their subsequent Williamson etherification in the
presence of the expensive 2,6-di-tert-butylpyridine or 2,6-di-
tert-butyl-4-methylpyridine proton traps.7d,16
repeat unit that exhibits only two conformers (trans and gauche)
a structural requirement for the design of self-assembling
amphiphilic dendrons employed in the construction of functional
supramolecular architectures exhibiting 3D internal order, or
are the repeat units that allow more than two conformers
sufficient for this self-assembly process?15 To answer this
question, the number of methylene groups was increased from
one in benzyl ether-based building blocks to three. This led to
the design and synthesis of the homologous series of ABn (n )
1, 2, 3) 3-phenylpropyl building blocks. This selection was based
on the hypothesis that the all trans-benzyl ether and phenyl-
propyl ether dendrimers can adopt closely related conformations.
This article reports the synthesis of three libraries of 3-phenyl-
propyl ether dendrons and the structural and the retrostructural
analysis of their supramolecular dendrimers8b,9,15 and compares
their self-assembly with that of the homologous libraries of self-
assembling benzyl ether dendrons.8b
This article addresses one of the most fundamental questions
of the self-assembling benzyl ether dendrons. Is the benzyl ether
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Results and Discussion
Synthesis of Dendritic Building Blocks. 4-Hydroxy, 3,4-
dihydroxy, 3,5-dihydroxy, and 3,4,5-trihydroxy-substituted meth-
yl 3-(phenyl)propionate building blocks are most conveniently
accessible by the catalytic reduction of the benzyl ether protected
or unprotected hydroxy-substituted methyl or ethyl cinnamates.
The precursor cinnamic acid derivatives are synthesized by the
Wittig reaction of the benzyl ether protected or unprotected
hydroxy benzaldehydes17 or by the Knoevenagel18 condensation
of the same derivatives with malonic acid followed by esteri-
fication.19 Alternatively, the 4-hydroxy-substituted 3-phenyl-
propionates can be synthesized from their protected 4-hydroxy-
substituted benzyl chloride by the malonic ester synthesis.20
After considering the methods available in the literature, we
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J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3325

A R T I C L E S
Percec et al.
Scheme 1. Synthesis of the First-Generation Dendritic Building Blocksa
a Reagents and conditions: (i) morpholine, AcOH, reflux; (ii) H2SO4 cat./MeOH, reflux; (iii) H2, Pd/C, EtOH; (iv) BnCl, DMF, 80 °C; (v) LiAlH4, THF;
(vi) PCC, CH2Cl2, 1 h.
Scheme 2. Synthesis of the First-Generation Dendronsa
a Reagents and conditions: (i) K2CO3, DMF, 80 °C; (ii) LiAlH4, THF (95-98%); (iii) CBr4, PPh3, CH2Cl2 (90-98%); (iv) 1. KOH, THF/EtOH; 2.
H2SO4 1 M (88-90%).
developed the strategy outlined in Scheme 1 for the synthesis
of the required building blocks. Due to their unsatisfactory purity
and high price, the commercially available 4-hydroxy and 3,4-
dihydroxy 3-phenylpropionic acids were also synthesized by
this method. The strategy outlined in Scheme 1 represents a
modified and improved procedure of a previously reported
method.19d
The synthesis of 5 does not involve protective groups since
the inexpensive 1 is commercially available in satisfactory
purity. The preparation of 12a, 12b, and 12c started from the
commercial 6a, 6b, and 6c that were used as building blocks
for the synthesis of self-assembling dendritic benzyl ethers.7d
Their hydroxy groups were protected as benzyl ethers. Reduction
of 7a, 7b, and 7c with LiAlH4 produced 8a, 8b, and 8c.
Oxidation of 8a, 8b, and 8c with PCC21 and the Knoevenagel
condensation of resulting 9a, 9b, and 9c with malonic acid
produced 10a, 10b, and 10c, which were esterified under acidic
conditions to yield 11a, 11b, and 11c. Catalytic hydrogenation/
hydrogenolysis of 11a, 11b, and 11c with Pd/C in ethanol
cleaved their benzyl ether protective groups and simultaneously
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3326 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

AB3 and AB2 Phenylpropyl Ether-Based Dendrimers
A R T I C L E S
Scheme 3. Synthesis of Higher-Generation Dendronsa
a Reagents and conditions: (i) K2CO3, DMF or DMF/THF, 75 °C; (ii) LiAlH4, THF; (iii) CBr4, PPh3, CH2Cl2.
hydrogenated their double bond to produce 12a, 12b, and 12c.
The overall yields for the multistep synthesis outlined in Scheme
1 ranged from 63 to 70%.
iterative process that consists of a combination of two different
methods used previously in our laboratory.6c,7d The first step
consists of the O-alkylation of 5, 12b, and 12c with 1-bromo-
dodecane. The reduction of 13a, 13b, and 13c with LiAlH4 and
bromination of 14a, 14b, and 14c with CBr4/PPh36b,c,22 produced
Synthesis of First-Generation Dendrons. The synthesis of
first- (Scheme 2) and higher-generation dendrons involves an
9
J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3327

A R T I C L E S
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Scheme 4. Retrostructural Analysis of 2D Smectic (S), p2mm Simple Rectangular Columnar (Φr-s), c2mm Centered Rectangular Columnar
(Φr-s), and p6mm Hexagonal Columnar (Φh), and Analysis of 3D 12-Fold Quasi-Liquid Crystal (QLC), Pm3hn Cubic (Cub), and P42/mnm
Tetragonal (Tet) Lattices
15a, 15b, and 15c. Etherification of 12b and 12c with 15a and
subsequent transformation of the -CO2CH3 group from the apex
into -COOH, -CH2OH, and -CH2Br produced the first-
generation dendrons 16a, 16b, 16c, 16d and 17a, 17b, 17c, 17d.
Synthesis of Higher-Generation Dendrons. The first-
generation dendrons 15b, c, 16c, and 17c (Scheme 2) were used
to construct the periphery of the higher-generation constitutional
isomeric 3,4- and 3,5-substituted AB2 and 3,4,5-substituted AB3
dendrons by the O-alkylation of 12a, 12b, and 12c (Scheme
3). Four new dendrons containing the -CO2CH3 group at the
apex are created in each library at each generation. Subsequent
hydrolysis and reduction of the -CO2CH3 followed by the
bromination of the resulting -CH2OH produced 12 additional
dendrons per library at each generation. Therefore, 16 new
dendrons are produced at each generation in each of the three
libraries. This sequence was repeated to construct up to four
generations of phenylpropyl ether-based dendrons.
Structural and Retrostructural Analysis of the AB3
Library of Supramolecular Dendrimers. Structural and ret-
rostructural analysis of the supramolecular dendrimers was
carried out by a combination of analytical methods that involve
1H and 13C NMR, MALDI-TOF, gel permeation chromatogra-
phy (GPC), differential scanning calorimetry (DSC), thermal
optical polarized microscopy (TOPM), experimental density
(F20), and small- and wide-angle X-ray diffraction (XRD)
experiments performed as a function of temperature on powder
and oriented fibers.6c,7c,d,8b,9,11,13a,b Scheme 4 outlines the concept
of retrostructural analysis of the periodic and quasi-periodic
lattices of supramolecular dendrimers. All experimental details,
analytical results, and calculation methods of this process are
available in the Supporting Information.
groups at their apex. We will discuss first the analysis obtained
from powder XRD at small and wide angles. The most
representative results for the AB3 library are summarized in
Scheme 5. They include the nature of the lattice, the diameter
(D) of the supramolecular column or sphere, the solid angle
(R′) of the dendron, and the number of dendrons (µ) forming a
sphere or a 4.7 Å cross section of a column. Complete analysis
is available in the Supporting Information. The first important
result is that all phenylpropyl dendrons self-assemble into
supramolecular dendrimers regardless of their generation,
functional group at the apex, and their AB2 or AB3 internal and
periphery architectures (Supporting Information Figures SF1-
SF12, Supporting Information Tables ST7-ST9). In the case
of related architectures generated from benzyl ether dendrons,
self-assembly was not observed at the first generation for the
(3,4,5)12G1-X and (3,4)12G1-X dendrons regardless of the
nature of X.8b The benzyl ether dendron (4-3,4,5)12G1-X self-
assembles only when X ) -COOH.8b
The second important result provided by the phenylpropyl
library is the lower transition temperature exhibited by their
supramolecular dendrimers. In the case of benzyl ether dendrons
at high generations, their transition temperatures were close to
or even higher than the decomposition temperature.8b
A
comparison of the results in Scheme 5 with the results from
Scheme 6 of ref 8b also demonstrated that the phenylpropyl
dendrons exhibit a higher tendency toward self-assembly into
supramolecular columnar structures than the corresponding
benzyl ether dendrons. For example, (3,4,5Pr)12G1-X self-
organizes into smectic and columnar supramolecular structures.
At low temperatures, even (3,4Pr-3,4,5Pr)12G2-X self-as-
sembles into supramolecular columns. The corresponding first-
generation benzyl ether dendrons do not assemble, while the
second generation self-assembles only in supramolecular spheres.8b
Various columnar structures were also observed for the first
and second generations based on (4Pr-(3,4,5Pr)n)12Gn-X and
The structural and retrostructural analysis was carried out at
each generation on supramolecular dendrimers self-assembled
from dendrons containing -CO2CH3, CH2OH, and -COOH
(22) Verheyden, J. P. H.; Moffatt, J. G. J. Org. Chem. 1972, 37, 2289-2299.
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AB3 and AB2 Phenylpropyl Ether-Based Dendrimers
A R T I C L E S
Scheme 5. Retrostructural Analysis of Supramolecular Dendrimers Self-Assembled from AB3 3,4,5-Trisubstituted Dendrons
(4Pr-3,4Pr-(3,4,5Pr)n-1)12Gn-X. At higher generations, all
dendrons from this library self-assemble into supramolecular
spheres that self-organize in quasi-liquid crystal (QLC)11b and
Pm3hn cubic7d lattices. Last but not least all phenylpropyl
supramolecular dendrimers exhibit diameters (D) that are with
up to 16 Å larger than those of the benzyl ether homologous.
For the same supramolecular structure, D increases with n and
for the same n with the increase in µ or decrease in R′. A new
unknown lattice was discovered for the case of (3,4,5Pr)212G2-
CO2CH3.
The first two series of dendrons from the benzyl ether library
self-assemble only in supramolecular spheres regardless of X
but only at generations two and higher. The last series of benzyl
ether dendrons self-assemble only at first generation in su-
pramolecular columns. (3,4,5Pr-3,4Pr)12G2-X provides the
largest diversity of supramolecular columns and spheres only
by changing the structure of X. This is the first dendron that
self-assembles into spheres that self-organize into Pm3hn cubic,7d
QLC,11b and P42/mnm tetragonal11a lattices. The compound with
X ) COOH self-assembles at low temperature in a column
while at high temperature in a sphere that self-organizes in the
tetragonal lattice. At n ) 2 and 3, all phenylpropyl dendrons
self-assemble into supramolecular spheres that self-organize in
the Pm3hn cubic lattice.
Structural and Retrostructural Analysis of the 3,4-
Disubstituted Library of AB2 Supramolecular Dendrimers.
The difference between phenylpropyl and benzyl ether dendrons
is even more striking in the case of the 3,4-disubstituted AB2
library. This can be observed by comparing the data from
Scheme 6 with the results reported in Scheme 4 from ref 8b.
Columnar structures are self-assembled from (3,4,5Pr-(3,-
4Pr)n-1)12Gn-X, (3,4Pr)n12Gn-X, and (4Pr-(3,4Pr)n)12Gn-X
for n ) 1 and 2 regardless of X, and for (4Pr-3,4,5Pr)12G1-X.
It is important to observe that at the same generation the
spheres self-assembled from phenylpropyl dendrons have a
diameter that can be up to 25 Å larger than that of the
corresponding benzyl ether-based supramolecular spheres. At
the same generation number, the diameter of the supramolecular
9
J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3329

A R T I C L E S
Percec et al.
Scheme 6. Retrostructural Analysis of Supramolecular Dendrimers Self-Assembled from AB2 3,4-Disubstituted Dendrons
structure generated from the 3,4-disubstituted dendrons (Scheme
6) is larger than that of the similar structure self-assembled from
3,4,5-trisubstituted dendrons (Scheme 5). The dependence of
D on n, µ, and R′ follows the same trend in both libraries. As
in the case of the previous library, a new unknown lattice was
discovered in the case of (3,4,5Pr-3,4Pr)12G2-CO2CH3. The
phenylpropyl dendrons have a smaller solid angle than the
benzyl ether dendrons, increasing the probability of generating
hollow supramolecular structures.
supramolecular sphere that generates the P42/mnm tetragonal
lattice.11a
All other dendrons self-assemble into various columnar and
smectic structures. This trend is in agreement with that observed
in the case of the benzyl ether library.8b However, the diversity
of column shapes, sizes, and lattices resulting from the phe-
nylpropyl dendrons is much larger than the diversity that resulted
from the benzyl ether dendrons. For example, in the case of
the phenylpropyl dendrons p6mm hexagonal columnar (Φh),
p2mm simple rectangular columnar (Φr-s), and c2mm centered
rectangular columnar (Φr-c), periodic arrays were obtained,
while in the case of benzyl ether dendrons only the Φh lattice
was observed.8b In addition, the dimensions of the current
supramolecular columns can be up to 140 Å larger ((4Pr-3,-
4Pr-3,5Pr)12G2-CO2CH3) than that of the corresponding benzyl
ether dendron.8b An additional characteristic that must be
mentioned is the faster dynamics of self-assembly mediated by
the more flexible phenylpropyl dendrons when compared with
the corresponding benzyl ether dendrons. This dynamics
facilitates the assembly of higher-order structures with phenyl-
propyl dendrons.
Structural and Retrostructural Analysis of the 3,5-
Disubstituted Library of AB2 Supramolecular Dendrimers.
Scheme 7 summarizes the structural and retrostructural analysis
of supramolecular dendrimers self-assembled from 3,5-disub-
stituted dendrons. As in the previous two libraries, all com-
pounds self-assemble regardless of n and X. This contrasts the
benzyl ether homologous library (Scheme 5, ref 8b). For
example, the first-generation benzyl ether homologues of (3,4,-
5Pr)12G1-X and (3,4Pr)12G1-X do not self-assemble. Two new
structures were discovered in the (3,4,5Pr)-(3,5Pr)n-1)12G2-X
series with n ) 2, X ) CO2CH3 and n ) 3, X ) CH2OH or
COOH. (3,4,5Pr-(3,5Pr)2)12G3-CO2CH3 self-assembles in a
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3330 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

AB3 and AB2 Phenylpropyl Ether-Based Dendrimers
A R T I C L E S
Scheme 7. Retrostructural Analysis of Supramolecular Dendrimers Self-Assembled from AB2 3,5-Disubstituted Dendrons
Dimensions of Supramolecular Dendrimers and Their
Solid Angle. Previously, we have reported that the dimensions
of the columnar and spherical supramolecular dendrimers
correlate with the solid angle (R) or the projection of the solid
angle (R′) of the self-assembling dendron.7g The solid angle
determines the shape of the dendron and the number of the
dendrons (µ) that self-assemble to generate a supramolecular
sphere or the 4.7 Å cross section of a supramolecular column.8b,9
Both R and µ change as a function of generation number of the
dendron and at the same generation as a function of dendron
architecture. The values of R and µ are obtained by the
retrostructural analysis of the supramolecular dendrimers and
are reported in Schemes 5-7. Recently, it has been demonstrated
that, in porous supramolecular columns self-assembled from
dendritic dipeptides,15b,23 R and µ correlate the dendron archi-
tecture with the pore diameter. When the generation number,
n, increases, R increases and µ decreases until ultimately µ
becomes equal to 1. When µ ) 1, the dendron is equal to a
sphere, and therefore, the dendron becomes a dendrimer.7h
Therefore, the control of the solid angle of the dendron
represents one of the most challenging architectural design
principles that must be elucidated to advance the complexity
(23) (a) Percec, V.; Dulcey, A. E.; Peterca, M.; Ilies, M.; Ladislaw, J.; Rosen,
B. M.; Edlund, U.; Heiney, P. A. Angew. Chem., Int. Ed. 2005, 44, 6516-
6521. (b) Percec, V.; Dulcey, A.; Peterca, M.; Ilies, M.; Miura, Y.; Edlund,
U.; Heiney, P. A. Aust. J. Chem. 2005, 58, 472-482. (c) Percec, V.; Dulcey,
A. E.; Peterca, M.; Ilies, M.; Sienkowska, M. J.; Heiney, P. A. J. Am.
Chem. Soc. 2005, 127, 17902-17909. (d) Percec, V.; Dulcey, A. E.; Peterca,
M.; Ilies, M.; Nummelin, S.; Sienkowska, M. J.; Heiney, P. A. Proc. Natl.
Acad. Sci. U.S.A. 2006, 103, 2518-2523.
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A R T I C L E S
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Table 1. XRD Data and Dpore Values for Selected Supramolecular Porous Columns
d10a (Å)
(A10b au)
d11a (Å)
(A11b au)
d20a (Å)
(A20b au)
d21a (Å)
(A21b au)
compound
T (°
C)
a
)
Dcol (Å)
Dpore (Å)
µ
(4Pr-(3,4Pr)2)12G2-CO2CH3
45
60
60
67
80
65
73
100
33
30
40
58.3
(42.6)
58.1
(54.8)
57.3
(59.8)
63.6
(51.2)
62.8
(51.7)
64.2
(54.9)
58.3
(55.9)
57.0
(55.9)
53.7
33.6
(25.1)
33.1
(22.8)
32.7
(19.8)
36.6
(19.8)
36.2
(22.0)
36.9
(19.2)
33.6
(20.8)
32.8
(21.3)
30.9
29.0
(20.3)
28.7
(22.4)
28.5
(20.3)
31.7
(17.8)
31.3
(19.7)
32.0
(17.3)
29.0
(19.7)
28.4
(19.2)
26.8
21.9
(12.1)
-
70.6 ( 0.4
66.5 ( 0.4
65.8 ( 0.4
73.3 ( 0.4
72.4 ( 0.4
74.0 ( 0.4
67.2 ( 0.4
65.7 ( 0.4
62.0 ( 0.4
62.5 ( 0.4
51.4 ( 0.4
12.9 ( 1.8
8.2 ( 1.4
6.6 ( 1.4
8.2 ( 1.4
7.8 ( 1.6
7.1 ( 1.7
7.8 ( 1.6
6.8 ( 1.4
4.1 ( 2.0
4.2 ( 1.8
2.0 ( 0.5
8
7
6
4
4
4
7
4
2
2
6
(4Pr-(3,4Pr)2)12G2-CH2OH
(4Pr-(3,4Pr)2)12G2-COOH
-
(4Pr-3,4Pr-(3,5Pr)2)12G3-CO2CH3
(4Pr-3,4Pr-(3,5Pr)2)12G3-CH2OH
(4Pr-3,4Pr-(3,5Pr)2)12G3-COOH
(4Pr-3,4Pr-3,5Pr)12G2-CH2OH
(4Pr-3,4Pr-3,4,5Pr)12G3-CH2OH
(4Pr-3,4,5Pr-(3,5Pr)2)12G3-CO2CH3
(4Pr-3,4,5Pr-(3,5Pr)2)12G3-CH2OH
(3,4Pr-3,5Pr)12G2-CH2OH
24.0
(11.1)
23.7
(6.6)
24.2
(8.5)
21.9
(3.5)
21.5
(3.6)
20.3
(3.6)
20.5
(5.4)
-
(60.2)
54.2
(61.3)
44.6
(19.8)
31.2
(18.6)
25.7
(16.4)
27.0
(14.7)
22.3
(74.4)
(15.9)
(9.6)
a d-Spacings of the Φh phase. b Peak amplitude scaled to the sum of the observed diffraction peaks between parentheses (au ) arbitrary units).
Figure 2. Wide-angle XRD patterns of aligned samples. (a, b) Tilt transition
and Dcol change observed for the (4Pr-3,4Pr-3,4,5Pr)12G2-X (X )
-COOH, -CH2OH, -CO2CH3) with X ) COOH. (c) Φhio phase of (4Pr-
(3,4Pr)2)12G2CH2OH. (d) Small-angle XRD pattern indicating the fiber
alignment and the first three reflections of the hexagonal phase. t ) dendron
io
tilt angle; (hk0) ) high-order reflections of the Φh phase; h1 and h2
)
long-range helical features with estimated correlation length ∼13 layers.
in R′ and an increase in µ for the phenylpropyl dendrons. The
outcome of this result provides a higher than expected increase
in the dimension of the supramolecular dendrimer at the
transition from benzyl ether to phenylpropyl ether-based su-
pramolecular dendrimers. This result, together with the higher
flexibility and lower transition temperatures, suggests architec-
tural pathways to supramolecular dendritic architectures larger
than those reported in previous publications8b,9 and in the current
report. However, in some cases mentioned during the retro-
structural analysis of the libraries of phenylpropyl dendrons,
Figure 1. (a) Representative small-angle XRD stack plots of supramolecular
porous columns with small and large Dpore. Reconstructed electron density
maps of the hollow hexagonal (b) and proposed hollow-centered rectangular
phases of (4Pr-3,4Pr-3,5Pr)12G2-CH2OH (c). a and b are lattice dimensions;
q ) 4π sin θ/λ; θ ) X-ray diffraction angle; λ ) 1.54 Å is the X-ray
wavelength; and a.u. ) arbitrary units.
and control the size of hollow and nonhollow supramolecular
dendrimers. An inspection of R′ and µ values from Schemes
5-7 and their comparison with the values obtained for the
homologous benzyl ether dendrons reveal a substantial decrease
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3332 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

AB3 and AB2 Phenylpropyl Ether-Based Dendrimers
A R T I C L E S
Figure 3. Increased order due to H-bonding interactions observed in (3,4Pr-3,4,5Pr)12G2-X; wide-angle XRD patterns of aligned samples collected at the
temperature indicated on the figure. (a,b,c) The bottom patterns are the same as the top ones shown with enhanced contrast. (d) For X ) COOH azimuthal
plots at the t feature q radius (blue) and at the h1 feature q radius (green). (e) Supramolecular helical hexagonal columnar assembly packing of (3,4Pr-3,4,-
5Pr)12G1-CH2OH. (10), (hk0) ) reflections of the hexagonal columnar phase; Chi ) azimuthal angle; t ) dendron tilt angle; e ) strong equatorial diffuse
reflection; h1, h2 ) long-range order helical features. The estimated correlation length is ∼75 Å and corresponds to about 15 layers.
unexpectedly large supramolecular dendrimers have been en-
countered. Their size indicates that hollow supramolecular
columns and even hollow spheres may be accessible without
the presence of the dipeptide functionality at the dendron apex,
since a combination of a decreased R and increased µ must
correlate with an increased hollow volume or pore diameter of
the supramolecular structure.15b,23
in both symmetric and asymmetric columns (Figure 1a and
Supporting Information). The circular symmetric columns self-
organize in a Φh lattice, while the ovoidal asymmetric columns
self-organize in a Φr-c lattice. The electron density maps of
both lattices were calculated and are shown in Figure 1b and c.
They indicate porous structures for both lattices. However, since
a calculation method for Dpore generated from ovoidal columns
is not yet available, the dimensions of ovoidal pores cannot be
determined.
Helical Porous Supramolecular Columns. The columnar
hexagonal (Φh) lattice generated from columns containing a pore
in their center can be identified by increased intensities of the
higher-order 11, 20, and 21 diffraction peaks.15b,23 A method
to calculate the pore diameter of porous columns was
elaborated.15b However, methods to calculate the pore size of
the ovoidal columns that self-organize in rectangular lattices
and of supramolecular spheres are not yet available. Therefore,
an inspection of the powder XRD diffractograms can im-
mediately identify hollow structures and provide the data
required to calculate the pore diameter of the supramolecular
columns self-organized in Φh lattices. A diversity of architec-
tures whose XRD indicates self-assembly into porous columns
was discovered in the libraries of phenylpropyl ether-based
dendrons. Selected examples from these structures, together with
their representative XRD data and their column (Dcol) and pore
(Dpore) diameters, are reported in Table 1 and Figure 1.
Figure 1a shows the XRD data of porous columns self-
assembled from (3,4Pr-(3,5Pr)2)12G3-CH2OH, (3,4Pr-3,-
5Pr)12G2-CH2OH, (4Pr-(3,4Pr)2)12G2-CO2CH3, and (4Pr-
3,4Pr-3,5Pr)12G2-CH2OH. The Dpore and the Dcol calculated
by simulating the XRD with the electron density of the dendron
are shown in the figure. Porous columns with Dpore between 2
and 13 Å are self-assembled from phenylpropyl dendrons
containing -CO2CH3, -COOH, and -CH2OH groups at their
apex (Table 1). (4Pr-3,4Pr-3,5Pr)12G2-CH2OH self-assembles
Enhanced Dynamics and Order. The high flexibility of the
phenylpropyl dendrons facilitates a faster dynamics of self-
assembly than that of the corresponding benzyl ether dendrons.
This mediates a higher degree of order in the supramolecular
assemblies generated from phenylpropyl dendrons. This dynam-
ics is observed despite temperatures lower than those of benzyl
ether dendrons and can be detected by both DSC and XRD
analysis. A comparison of the enthalpy and entropy changes
(∆H and ∆S) associated with the transition from ordered
periodic arrays of supramolecular dendrimers to their disordered
liquid state for phenylpropyl and benzyl ether based structures
is available in Supporting Information Table ST10. These data
demonstrate that for the same phase transition both the enthalpy
and entropy changes are up to 30 times larger in the case of
phenylpropyl dendrons. As a consequence of the enhanced
dynamics and order, much shorter annealing is required in the
case of phenylpropyl dendrons to reach equilibrium states in
DSC and XRD experiments. The columnar hexagonal structures
exhibited by (3,4Pr-3,4,5Pr)12G2-X with X ) -CO2CH3,
-CH2OH, and -COOH are used to demonstrate this concept
(Figures 2, 3). The balance between flexibility, dynamics, and
enhanced stiffness induced by H-bonding in the core increases
the intracolumnar order at the transition from X ) -CO2CH3,
to -CH2OH, and to -COOH. This trend contrasts the results
9
J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3333

A R T I C L E S
Percec et al.
obtained with the less flexible benzyl ether-based dendrons when
strong interactions in the core of the dendron reduce the degree
of order of the supramolecular assembly.8b
ics of self-assembly into larger supramolecular structures with
higher order and lower transition temperatures than the corre-
sponding benzyl ethers. In addition to the discovery of a series
of novel and nonelucidated supramolecular structures, the
phenylpropyl ether library self-assembles, regardless of its
generation number and functional group at its apex, into all
nonhollow and hollow, periodic and quasi-periodic arrays that
were encountered previously with dendritic benzyl ethers8b,11
and dendritic dipeptides.15b,23 At the same generation number,
the solid angle of the phenylpropyl ether dendrons is lower than
that of the corresponding benzyl ether dendrons.8b This facili-
tated the assembly of supramolecular dendrimers with larger
dimensions at the same generation number, predicted the
potential synthesis of a higher number of generations of
dendrons, provided the largest diversity of tapered dendrons that
mediate self-assembly into helical columnar structures, and
facilitated the assembly of hollow columns and spheres without
the requirement of a dipeptide at the apex of the dendron.15b,23
Self-assembling tapered dendrons are much less often encoun-
tered than conical dendrons.8b,9 However, they are required to
elucidate the structural origin of functions.15 Therefore, this new
library of self-assembling dendrons and the architectural design
principles derived from it are expected to impact the field of
dendritic macromolecules1,5 and of self-organized soft complex
matter5,24 at both the fundamental and technological levels.
The effect of the increased conformational freedom of the
phenylpropyl dendrimers is exemplified by the XRD results
summarized in Figure 2a and b. A dendron tilt transition was
observed for the first time in the supramolecular structure of
this phenylpropyl-based dendron. The XRD fiber experiments
of the (4Pr-3,4Pr-3,4,5Pr)12G2-X-based supramolecular den-
drimers show that the dendron tilt angle changes from 30° at
room temperature (Figure 2a) to 21° at 65 °C (Figure 2b). At
both temperatures, the supramolecular assemblies are in co-
lumnar hexagonal phase. Dcol increases more than 10% between
these temperatures. This is in agreement with the change
observed for the dendron tilt angle. It is remarkable that this
tilt transition is observed in the DSC scans as well (see
Supporting Information Figure 24).
Another important effect caused by the flexibility of the
phenylpropyl dendrons is illustrated by Figure 3. The compari-
son of the dendrimer hexagonal intracolumnar ordered phase
generated from (3,4Pr-3,4,5Pr)12G2-X indicates that the func-
tional group from their apex determines the degree of intraco-
lumnar order of their supramolecular structure. The H-bonding
interactions between the apex functional groups together with
the increased flexibility of the dendrimers are responsible for
the higher intracolumnar order. This can be seen by the increased
intensities of the high-order (hk0) reflections, of the equatorial
feature e, and the appearance of the h1, h2 helical features for
the case of X ) CH2OH and X ) COOH in Figure 3b and c.
The dendron tilt angle does not seem to be affected by the
functional groups from their apex. This indicates that the overall
3D packing is not significantly changed. An additional similar
example is presented in Supporting Information Figure 25.
Experimental Section
The synthetic methods and techniques are similar to those used
conventionally in our laboratory.8b,9,11,15 They are available in the
Supporting Information.
Acknowledgment. Financial support by the National Science
Foundation (DMR-0102459 and DMR-0548559) and the Office
of Naval Research is greatly acknowledged.
Conclusions
Supporting Information Available: Experimental procedures
with complete spectral, structural, and retrostructural analysis.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Three libraries, one of 3,4,5-trisubstituted AB3 and two of
constitutional isomeric 3,4- and 3,5-disubstituted AB2 self-
assembling phenylpropyl ether-based dendrons, were synthe-
sized. The structural and retrostructural analysis of their
supramolecular dendrimers facilitated the comparison of the self-
assembly of these three libraries of phenylpropyl dendrons with
those of the architecturally related benzyl ether dendrons.8b The
more flexible and stable, under both thermal and acidic
conditions, phenylpropyl ether dendrons exhibit a faster dynam-
JA060062A
(24) (a) Lehn, J.-M. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 4763-4768. (b)
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