Site-specific installation and study of electroactive units in every layer of dendrons

Article abstract of DOI:10.1021/jo902109u

(Graph Presented) Whereas encapsulation of functional groups at the core of dendrimers is well-understood, very little is known about their intermediate layers or even the periphery. Here we report on a systematic investigation of every layer of dendrimer

Full text of DOI:10.1021/jo902109u

pubs.acs.org/joc
Site-Specific Installation and Study of Electroactive Units in Every Layer
of Dendrons
Malar A. Azagarsamy, Kothandam Krishnamoorthy, Kulandaivelu Sivanandan, and
S. Thayumanavan*
Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003
thai@chem.umass.edu
Received October 15, 2009
Whereas encapsulation of functional groups at the core of dendrimers is well-understood, very little is
known about their intermediate layers or even the periphery. Here we report on a systematic
investigation of every layer of dendrimers by incorporating a single ferrocene unit in well-defined
locations in dendrons. Site-specific incorporation of the ferrocene unit was achieved by utilizing the
dendrimer sequencing methodology. We show here that the redox potential values of ferrocene at
intermediate layers were remarkably different from those at the core and the periphery. Although
redox potential values were location-dependent, no significant change in the rate of heterogeneous
electron transfer (k0) was observed with respect to locations. This was attributed to the possibility
that free rotation of dendrimer nullifies the distance between the electrode and ferrocene unit.
Finally, we also show that no Faradaic current was observed for the amphiphilic assemblies of these
dendrons, whereas the same dendron did exhibit significant Faradaic current in nonassembling
solvent environments.
Introduction
functionalizing them with photo-, electro-, and catalytically
active units for a variety of applications.2-4 Generally, these
Dendrimers, despite their complexities, are attractive
macromolecular architectures as they can be obtained with
well-defined molecular weights and a precise number of
functional groups.1 Because dendrimers become globular
at higher molecular weights, there has been an interest in
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DOI: 10.1021/jo902109u
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Azagarsamy et al.
JOCArticle
active units are incorporated either at the core, where there is
significant encapsulation and protection from the environ-
ment, or at the periphery of dendrimers, where opportunity
exists for loading a large number of functional moieties.2-6
While there have been comparisons between the solvent-
exposed peripheral functionalities and the well-encapsulated
core functional groups, very little is known about the inter-
mediate layers in these molecules. Therefore, the microenvi-
ronment variations from the core to the periphery of the
dendrimers are not well understood.
Note that a significant amount of work has been pre-
viously reported on the encapsulation of electroactive func-
tionalities using dendritic scaffolds.2-6 These works have
specifically focused on understanding features such as the
effect of generational variations in dendrimers and the
nature of dendrimer backbones upon the encapsulation
efficiency of electroactive scaffolds incorporated at the core
or focal points of dendritic architectures. Our work here is
focused on understanding the change in encapsulation of an
electroactive functionality at the periphery, focal point, and
the intermediate layers of dendrons. One of the issues in
comparing different locations of a dendrimer involves the
variation in number density of the functional moieties in
different layers. For example, in a third generation mono-
dendron, the number of identical functional groups in the
periphery would be eight compared to a single focal point
moiety. There is a progressive variation in this number in the
intermediate layers. This variation significantly complicates
meaningful comparisons regarding the microenvironment
of different locations. An unambiguous way to address
this issue would be to incorporate a single active functional
group at a predetermined location of the dendrimer. To be
successful in such a venture, it is necessary that we access
synthetic methods that allow variations in the two Bs of an
AB2 monomer. In a preliminary communication,7 we had
incorporated a photoactive anthracene moiety at precise
locations within benzyl ether dendrons using the synthetic
methods we had developed previously.8 In that report, we
utilized Stern-Volmer quenching to probe the access of
guest molecules to various locations within dendrimers,
where we observed a precipitous change in the guest access
at the intermediate layers of the dendrimers. While those
findings provide insights in homogeneous solutions, it is
invaluable to also understand the accessibility of functional
groups in dendrimers in the context of heterogeneous elec-
tron transfer, since this provides more direct information on
encapsulation and dendritic shielding effects. Here, we re-
port on the design, syntheses, and electrochemical investiga-
tion of dendrons with a single ferrocene unit at different
locations.
Results and Discussion
Molecular Design and Synthesis. We chose to incorporate
ferrocene as the electroactive unit within these dendrons,
because its electrochemical behavior is well understood.5,6,9
We have utilized our recently reported biaryl dendrimers as
the scaffold, because of the additional phenyl ring, which
provides a handle to incorporate electroactive functionalities
(i.e., in addition to the AB2 functionalities necessary for the
dendritic growth).10 The biaryl dendrimers contain a car-
boxylic ester functionality on one face and a decyl moiety on
the other side in each of the repeat units within the den-
dron.10a To install a single ferrocene unit at a specific
location, one of the decyl units was replaced with a ferrocene
unit. The structures of dendrons up to third generation are
shown in Chart 1. It is important to reiterate that, within
these structures, there is only one ferrocene unit at any one
time. For example, in a G3 dendron, when the peripheral
layer contains a ferrocene unit (R4 = Fc derivative), all other
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n-C10H21). To easily follow the structures of the dendrons
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CHART 1. Structures of Functionalized Dendrons
CHART 2. Structures AB2 and ABBp Monomers
the first layer L1. Thus, for a G3 dendron, the focal point
functionalization would be G3(L1), while the functionaliza-
tion at the periphery would correspond to G3(L4) (see
Chart 1).
Although the structures targeted here are focused on
incorporation of ferrocene, we envisaged that it would be
useful to have a general synthetic strategy that allows for
functionalization of the dendrimer with versatile active units
at desired locations. Therefore, we were interested in a
modular synthetic scheme, where the ferrocene unit is in-
corporated in the final stage of the synthesis. For this
purpose, incorporation of a single reactive functionality that
can tolerate the reaction conditions the syntheses of biaryl
dendrimers is described. We have chosen an alkyne unit as
the reactive functionality so that any desired active unit
can be incorporated easily through the copper-catalyzed
Huisgen 1,3-dipolar cycloaddition, which is popularly
known as “click” chemistry.11
functionalization, whereas there are multiple identical loca-
tions in the periphery. For example, the G3 dendron
(Chart 1) contains eight identical peripheral units; here the
challenge resides in functionalizing only one of them.
To achieve this, we utilized our dendrimer sequencing
methodology that is based on protection-deprotection stra-
tegies.8b,c Since our dendrons are based on AB2 biaryl
repeating unit 1 (Chart 2),10a it is necessary to differentiate
the two B functionalities in order to introduce sequences
within the dendrimer. To execute this, one of the B function-
alities of AB2 should be protected and thus the targeted
monomer is designated as ABBp 2 (Chart 2). After reacting
the unprotected B functionality with one equivalent of A, the
protected B will be liberated and then reacted with a different
monomer. This allows for the incorporation of two different
A’s on to an AB2 building block. Based on this approach for
the synthesis of precisely functionalized dendrons (Chart 1),
Incorporation of a single functional unit at the periphery
of a dendron is more challenging than that at the focal point.
This is because the focal point has only one location for
(11) (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem., Int. Ed. 2002, 41, 2596. For a review on click chemistry, see:
(b) Lutz, J.-F. Angew. Chem., Int. Ed. 2007, 46, 1018. For the utilization of
click chemistry in dendrimers, see: (c) Wu, P.; Feldman, A. K.; Nugent, A.
ꢀ
K.; Hawker, C. J.; Scheel, A.; Voit, B.; Pyun, J.; Frechet, J. M. J.; Sharpless,
K. B.; Fokin, V. V. Angew. Chem., Int. Ed. 2004, 43, 3928.
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SCHEME 1. Synthesis of ABBp and AB2 Monomers
SCHEME 2. Synthesis of G0(L) Dendron and Its Bromide
to use the monoprotected ABBp monomer 2. To synthesize
the second generation G2(L3), monomer 2 was treated
with symmetrical G1-Br in the presence of K2CO3 and
the resultant compound was subjected to MOM-deprotec-
tion to afford the compound 10. The phenolic compound 10
was then treated with 11, obtained by the bromination of
G1(L2), to provide G2(L3) dendron. Similarly, treating the
ABBp monomer 2 with G2-Br followed by the deprotection
of MOM afforded the compound 12, which was further
treated with 13 to yield G3(L4) dendron as shown in
Scheme 3.
the main building blocks required are the AB2 biaryl unit 1,
and the ABBp unit 2, and the peripheral unit G0(L).
The syntheses of the building blocks 1 and 2 started with
tert-butyldimethylsilyl (TBS) protected aryl stannane 3 and
3,5-dihydroxy-4-bromobenzoic acid 4, following our pre-
vious reports to obtain the biaryl aldehyde 5.10a Deprotec-
tion of TBS groups followed by the reduction of aldehyde
provided the AB2 monomer 1. The bottleneck here involved
the monoprotection of AB2 monomer 1. Our initial trials to
monoprotect 1 using MOM-Cl in the presence of K2CO3 had
resulted in the hydrolysis of tert-butyl ester. When Hunig’s
base was used instead of K2CO3, there was no selectivity
toward the phenolic hydroxyl group over the primary ali-
phatic hydroxyl group. Finally, the monoprotection was
achieved on the biaryl aldehyde 6, thereby avoiding the
presence of the primary aliphatic hydroxyl group during
the protection step. The final reduction on the monopro-
tected aldehyde yielded the monomer ABBp 2 (Scheme 1).
The periphery G0(L) containing alkyne moiety was
synthesized by first mono-alkylating 3,5-dihydroxy benzyl
alcohol (7) with tert-butylbromoacetate in the presence
of potassium carbonate and 18-crown-6 (Scheme 2).
The mono-alkylated compound was further treated with
1-bromo-4-pentyne to afford G0(L). The resultant hydroxy-
methyl compound G0(L) was converted to its bromide 8
using a CBr4/PPh3 combination. Along with these building
blocks, we also require the bromides of symmetrical den-
drons G0-Br, G1-Br, and G2-Br (Chart 3), which were
synthesized following our earlier report.10a
Synthesis of dendrons with the functionality at the focal
point is relatively straightforward, except that it requires a
central core unit 14 that contains an alkyne moiety. The
synthesis of core unit 14 is outlined in Scheme 4. The key step
in the synthesis of this unit is the Stille coupling between the
MOM-protected aryl stannane 15 and aldehyde 16. The aryl
stannane 15 was obtained from commercially available
1-bromo-3,5-dimethoxybenzene 17 in three steps. The steps
involve the deprotection of methyl groups followed by the
protection of free hydroxyl groups using MOM-Cl. The
resultant MOM-protected bromobenzene was treated with
n-BuLi, followed by tributyltin chloride to obtain the aryl
stannane 15. On the other hand, the bottom ring 16 was
obtained from 4-bromo-3,5-dihydroxybenzoic acid 4, which
was first converted to the corresponding benzyl alcohol,
4-bromo-3,5-dihydroxybenzyl alcohol (Scheme 4). This
molecule was first treated with 1 equiv of tert-butyl bromo-
acetate to isolate the monosubstituted product. The product
was then subjected to PCC oxidation to yield the aldehyde
16. The 4-bromobenzaldehyde 16 and aryl stannane 15 were
then subjected to the palladium(II)-catalyzed Stille coupling
reaction to achieve the biaryl compound. The biaryl com-
pound was further treated with 1-bromo-4-pentyne followed
by the reduction of the aldehyde and the final deprotection of
the MOM groups, yielding the monomer 14. The core
functionalized first generation G1(L1) was synthesized by
treating monomer 14 with 2 equiv of G0-Br as shown in
Scheme 5. Similarly, the second and third generation den-
drons, G2(L1) and G3(L1), were obtained by treating mono-
mer 14 with G1-Br and G2-Br, respectively (Scheme 5).
Functionalizing the intermediate layers also requires the
sequencing methodology. It is important to note that the G2
dendron has only one intermediate layer, whereas the G3
dendron has two intermediate layers. Thus three totally
different dendrons, G2(L2), G3(L2), and G3(L3), had to be
synthesized. As shown in Scheme 6, the synthesis of G2(L2)
The first generation dendron G1(L2) (Chart 1) was synthe-
sized by sequentially introducing two different peripheral
units. The monomer 1 was first treated with a stoichiometric
amount of G0-Br to get monosubstituted compound 9,
which was further treated with bromide 8 to obtain G1(L2)
(Scheme 3). Note that here we did not utilize our protec-
tion-deprotection strategy, because of the easy separation
of monosubstituted compound from a mixture of products.
However, the separation was cumbersome in the case of the
second and third generation dendrons. Thus we have decided
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CHART 3. Structures of G0-Br, G1-Br, and G2-Br
SCHEME 3. Synthesis of Peripherally Functionalized Dendrons
was accomplished by first converting the core functionalized
lower generation G1(L1) to its bromide using a CBr4/PPh3
combination and then treating the bromide with com-
pound 10. Similarly, other dendrons G3(L2) and G3(L3)
were synthesized by bromination of corresponding second
generation dendrons and subsequent treatment with com-
pound 12 (Scheme 6).
After the site-specific incorporation of the acetylene
moiety into the dendrons, we moved on to install the
ferrocene unit through click chemistry. Treatment of these
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SCHEME 4. Synthesis of Acetylene-Functionalized Monomer
SCHEME 5. Synthesis of Functionalized Dendrons at the Focal
Point
SCHEME 7. Incorporation of Ferrocene into the Alkyne Con-
taining Dendrons through Click Chemistry
redox potential of the ferrocene unit (118 mV for the focal
point and 114 mV for the peripheral layer). However,
the relative E1/2 values of the G2 and G3 dendrons were
interesting. In the case of G2, the redox potentials of the focal
point and the peripheral layer were similar to those observed
with G1. However, the E1/2 of the ferrocene functionality
placed at the intermediate layer in this dendron was found to
SCHEME 6. Synthesis of Intermediate Layer Functionalized
Dendrons
acetylene-containing dendrons with azidomethyl ferrocene
in the presence of a catalytic amount of copper sulfate and
sodium ascorbate afforded the corresponding triazole deri-
vatives as exemplified in Scheme 7. Structures of these
ferrocene-incorporated dendrons are shown in Chart 1. All
1
these dendrimers were characterized using H NMR, 13C
NMR, and matrix-assisted laser-desorption time-of-flight
(MALDI-TOF) mass spectrometry.12
Electrochemical Studies. The electrochemical properties of
the ferrocene-incorporated dendrons were investigated using
cyclic voltammetry. Cyclic voltammograms (CV) were re-
corded in DMF using 10 μm platinum disk as the working
electrode, Pt wire as counter electrode, and Ag/Agþ as
reference electrode.12 All dendrons showed the s-shaped
steady state CV (see Figure 1 for example) anticipated in
microelectrode-based experiments. The redox potentials
(E1/2) obtained for the ferrocene unit in these dendrons are
shown in Table 1. In all these cases, the nondendron molecule
G0 could be considered as the control, which exhibited an
E1/2 of about 103 mV. The two layers in the lowest generation
dendrons, G1, did not show any significant difference in the
FIGURE 1. Steady-state cyclic voltammogram of G3(L2)Fc in
DMF.
TABLE 1. Electrochemical Data for Non-amphiphilic Dendrons in DMF
dendrons
El/2
D0 (cm2/s)
k0 (cm/s)
G0(L)Fc
Gl(Ll)Fc
Gl(L2)Fc
G2(Ll)Fc
G2(L2)Fc
G2(L3)Fc
G3(Ll)Fc
G3(L2)Fc
G3(L3)Fc
G3(L4)Fc
103
118
114
113
69
117
101
60
5.1 ꢀ 10-6
2.0 ꢀ 10-6
2.0 ꢀ 10-6
1.0 ꢀ 10-6
1.0 ꢀ 10-6
l.0 ꢀ 10-6
1.1 ꢀ 10-6
1.1 ꢀ 10-6
1.1 ꢀ 10-6
1.1 ꢀ 10-6
1.9 ꢀ 10-4
1.8 ꢀ 10-4
3.1 ꢀ 10-4
1.5 ꢀ 10-4
1.9 ꢀ 10-4
1.4 ꢀ 10-4
1.4 ꢀ 10-4
1.5 ꢀ 10-4
1.8 ꢀ 10-4
1.7 ꢀ 10-4
68
120
(12) See Supporting Information for details.
9480 J. Org. Chem. Vol. 74, No. 24, 2009

Azagarsamy et al.
JOCArticle
FIGURE 2. Energy-minimized structures of G3 dendrons with ferrocene at different locations (ferrocene is shown in black and green colors).
be 69 mV, compared to 113 and 117 mV for the focal point
and the peripheral ferrocenes, respectively. A similar trend
was also observed with the G3 dendron. In this generation,
the ferrocene unit could be incorporated in four different
locations, as there are two intermediate layers. Once again,
the redox potential of the ferrocene incorporated at the
intermediate layer was found to be about 40-60 mV differ-
ent from those observed with the focal point and peripheral
functional groups (see Table 1). The E1/2 values of the
ferrocene at the intermediate layers were found to be 60
and 68 mV, compared to 101 and 120 mV for the focal point
and peripheral ferrocenes, respectively. Difference in E1/2
value is related to the thermodynamic stability differences
between the reduced and the oxidized state of the electro-
active molecule. The lower redox potentials, observed for an
otherwise identical ferrocene unit at the intermediate layers,
suggest that the ferrocenium ion product is more stabilized in
these intermediate layers compared to the peripheral func-
tionality. These could be taken to suggest that the ferrocene
units located in the intermediate layers are less solvent-
exposed compared to the focal point and the periphery. It
is also likely that the ferrocenium (Fe3þ) ion is better
stabilized by the dendrimer backbone compared to DMF.
This is an interesting observation with dendrons. Conven-
tional wisdom about dendrons and dendrimers suggest that
the focal point or core of these molecules provide signifi-
cantly different microenvironments, compared to the peri-
phery. With these studies, we clearly show that it is the
intermediate layers that behave significantly differently from
the focal point and periphery of the dendrons. A question is:
why not interpret these results to suggest that the ferrocenes
at the intermediate layers are more exposed to the solvent,
because the periphery is more crowded (sterically) and the
ferrocene unit is encapsulated at the core? The fact that the
E1/2 value in lower generation dendrons, where the ferrocene
unit is clearly more solvent-exposed, are closer to the peri-
pheral and focal point E1/2 values in higher generation
dendrons supports our explanation that the dendrimer back-
bone indeed facilitates the oxidation of ferrocene units in the
intermediate layers of the dendrons.
To visualize these dendrons, we obtained the energy-mini-
mized structures of G3 dendron using MM2 (Figure 2).
Interestingly, ferrocene functionality was enclosed by the
biaryl backbone in the case of G3(L3)Fc dendron that con-
tains ferrocene in the intermediate layer, while it was placed
out of the dendrimer backbone in dendrons that contain
ferrocene unit at the core and periphery. However, in contrast
to our interpretation, the ferrocene placed in the other inter-
mediate layer of G3(L2)Fc dendron seems to be still presented
at edge of dendrimer backbone. Note that these structures are
obtained by energy minimization in the gas phase and thus do
not account for the differential solvation of substituents. We
suggest this as the reason for the observed discrepancy.
Considering the differences in the thermodynamics of the
redox active species in different layers, we were also inter-
ested in investigating the kinetics of the heterogeneous
electron transfer reactions. As a first step toward the calcula-
tion of kinetic parameters, the diffusion coefficient (D0) was
calculated utilizing the limiting current obtained from the
steady-state CV for each of the generation. We had assumed
that within a generation the D0 would be identical, and thus
the estimation of D0 was achieved using the more abundantly
available focal point functionalized dendrons of each genera-
tion. As shown in Table 1, the D0 decreases upon increase
in generation number, which is the general trend observed
for dendrimers. The obtained D0 values were utilized to
J. Org. Chem. Vol. 74, No. 24, 2009 9481

Azagarsamy et al.
JOCArticle
rapidly near the electrode surface. Therefore, it is easy to
imagine that the rotation of the dendron leads to an orienta-
tion in which the ferrocene is equidistant from the electrode
in both G3(L1)Fc and G3(L4)Fc as illustrated in Figure 3.
Such orientations result in similar k0 values for both
G3(L1)Fc and G3(L4)Fc. The energy-minimized structures
in Figure 2 further supports this hypothesis. Similarly,
ferrocene in G3(L2)Fc and G3(L3)Fc are only one layer
away from G3(L1) and G3(L4), respectively. Hence, it is
possible that the k0 value is essentially unchanged. These
results show that the dendrimer growth does not effectively
shield the ferrocene unit from the electrode, although the
ferrocenium ion product is stabilized differently in various
layers of the dendrons.
FIGURE 3. Orientation of G3 dendron toward the electrode as a
result of its free rotation.
Finally, we were interested in studying the electrochemical
behavior of these ferrocene units in amphiphilic supramole-
cular assemblies that could be obtained from these dendrons.
An interesting feature about the biaryl-based dendrons is
that the hydrolysis of the tert-butyl esters would provide the
facially amphiphilic dendrons shown in Chart 4.12 We have
previously shown that these dendrons provide unique envi-
ronment-dependent assemblies.10a Therefore, the carboxylic
ester functional groups in the ferrocene-containing dendrons
above were hydrolyzed.14 To study the electrochemical
behavior of the ferrocene units incorporated within these
amphiphilic dendrons, these molecules were first dissolved in
water at a concentration above their respective critical
aggregation concentrations (CACs) to form the micellar
assemblies.
calculate the standard rate constants for heterogeneous
electron transfer (k0).13,5i
Whereas the D0 values were found to follow the general
trend, the k0 values did not vary significantly as a function of
generation number or the location of the ferrocene (Table 1).
All rate constant values were found to be about (1-2) ꢀ 10-4
cm/s. Similar k0 values for the first and second-generation
dendrons is perhaps not surprising (we do not have an
explanation for the slightly higher k0 for G1(L2)Fc). How-
ever, the insignificant changes in k0 of ferrocenes in various
layers of higher generation dendrons are surprising. This is
possibly due to the free rotation of the dendrons that leads to
an orientation in which the ferrocene is conveniently ac-
cessed by the electrode irrespective of its location. For
example, in the case of G3(L1)Fc and G3(L4)Fc, the ferro-
cene is at the core and at the periphery of the dendron,
respectively. It is reasonable that the dendrons could rotate
The electrochemical studies of these assemblies were then
performed using the platinum microelectrode as the working
electrode. We were surprised to find that there was no
CHART 4. Structures of Ferrocene Incorporated Amphiphilic Dendrons
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Azagarsamy et al.
JOCArticle
FIGURE 4. Cyclic voltammogram of (a) G3(L1)Fc-COOH in water and (b) G3(L1)Fc-COOH in DMF.
discernible features in the CV from the dendrons (Figure 4a).
The behavior was found to be rather capacitive in nature.
This observation could be due to one of the two following
reasons: (1) ferrocene has detached from the dendron or
became electro-inactive during the ester hydrolysis and work
up; (2) ferrocene is buried in the hydrophobic pocket of these
rather large micellar assemblies (∼40-100 nm). To distin-
guish these possibilities, we recorded the CV of the hydro-
lyzed dendron in DMF. Dynamic light scattering (DLS)
studies of these dendrons have confirmed that these amphi-
philic dendrons do not aggregate in DMF, since the solvent is
compatible with both the carboxylic acid and the decyl
functionalities. Therefore, we should observe a steady-state
CV if the ferrocene is intact and electro-active. Indeed, we did
observe a steady-state CV for the hydrolyzed dendron, which
confirms that the ferrocene is indeed electro-active and intact
(Figure 4b).
Experimental Section
General Procedure for Introducing Ferrocene Unit Using Click
Chemistry. To a solution of alkyne-functionalized dendrimers
(1.0 equiv) in THF/DMF/H2O (1:1:1), azidomethyl ferrocene
(4.0-8.0 equiv), CuSO4 (0.1 equiv), and sodium ascorbate
(0.1 equiv) were added. The reaction mixture was heated at
50 °C for 12 h. Progress of the reaction was monitored by
thin layer chromatography (TLC). After completion of the
reaction, the reaction mixture was partitioned between ethyl
acetate and saturated NH4Cl solution. The aqueous layer was
extracted twice with ethyl acetate, and the combined organic
layer was dried over anhydrous Na2SO4 and evaporated to
dryness. The crude product was isolated by silica gel column
chromatography.
Synthesis of G0(L)Fc. According to the general procedure for
click chemistry, G0(L) (0.1 g, 0.31 mmol) was treated with
azidomethyl ferrocene (4 equiv) to yield 0.14 g (80%) of
1
G0(L)Fc. H NMR (400 MHz, CDCl3) δ 7.19 (s, 1H), 6.51 (s,
1H), 6.47 (s, 1H), 6.34 (t, J = 2.4 Hz, 1H), 5.22 (s, 2H), 4.58 (d,
J = 4.0 Hz, 2H), 4.46 (s, 2H), 4.24 (t, J = 1.6 Hz, 2H), 4.19-4.16
(m, 7H), 3.92 (t, J = 6.0 Hz, 2H), 2.81 (t, J = 7.2 Hz, 2H), 2,43,
(bs, 1H), 2.12-2.05 (m, 2H), 1.47 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 168.0, 160.2, 159.1, 147.0, 143.7, 120.4, 106.1, 104.9,
100.7, 82.4, 81.1, 77.4, 77.3, 77.1, 76.8, 69.0, 68.9, 66.9, 65.7,
65.0, 49.9, 28.8, 28.1, 22.1; FAB/MS m/z (r.i.) 561(Mþ, 40),
362(15), 307(20), 199(100); HRMS (FABþ) calcd for C29H35Fe-
N3O5 561.1927, found 561.1942.
It is also interesting to note that although there was no
significant faradaic current from the micellar assemblies of
all the amphiphilic dendrons, the small molecule surfactant
G0(L)Fc-COOH displayed a steady-state CV. A possible
explanation for this is that, in the case of small molecule
surfactant G0(L)Fc-COOH, there exists
a significant
amount of free monomeric surfactant in solution due to
the rather fast equilibrium between the small molecule and
the micellar assembly. As a result, the ferrocene would be
easily available for electron transfer in the monomeric
surfactants, accounting for the observed voltammetric re-
sponse. On the other hand, the dendrons form more tightly
packed assemblies due to the covalent linking of the mono-
meric units. Thus, the concentration of monomeric dendritic
units would be too low in solution to be observable. Similar
observations, in which no significant electron transfer was
seen when ferrocene was encapsulated in a hydrophobic
host, were reported recently.14 Nonetheless, these results
show that the amphiphilic assemblies provides an interesting
pathway for fully silencing an electroactive unit, which can
then be released to become electroactive in an alternate
environment, i.e., from water-like to DMF-like environ-
ment.
Synthesis of G1(L2)Fc. The alcohol G1(L2) (0.05 g, 0.08
mmol) was subjected to click reaction as per the general proce-
dure to yield 0.055 g (92%) of G1(L2)Fc. 1H NMR (400 MHz,
CDCl3) δ 7.50 (s, 1H), 6.96-6.40 (m, 11H), 5.33-5.22 (m, 2H),
4.92 (s, 4H), 4.66 (s, 2H), 4.47-4.41 (m, 7H), 4.30-4.10 (m, 8H),
3.90 (m, 6H), 2.84 (bs, 2H), 2.29-1.18(m, 61H), 0.88-0.81 (m,
6H); 13C NMR (100 MHz, CDCl3) δ 168.0, 167.8, 160.3, 160.0,
159.0, 156.9, 155.8, 147.0, 141.8, 139.5, 135.5, 119.2, 110.1,
107.0, 105.4, 105.3, 104.8, 103.5, 101.0, 100.7, 82.2, 82.0, 69.9,
69.5, 68.7, 68.0, 66.8, 66.2, 65.7, 65.3, 49.6, 31.8, 29.5, 29.4, 29.3,
29.2, 29.1, 28.9, 28.0, 25.9, 22.5, 22.0, 14.0; MALDI-TOF m/z
1422.9, 1445.7 (C81H111FeN3O15 requires 1422.6 and
C81H111FeN3O15 þ Naþ requires 1445.6).
Synthesis of G2(L3)Fc. According to the general procedure
for click reaction, G2(L3) (0.08 g, 0.3 mmol) was reacted with
azidomethyl ferrocene (6.0 equiv) to yield 0.08 g (93%) of
G2(L3)Fc. 1H NMR (400 MHz, CDCl3) δ 7.20 (s, 1H),
6.77-6.39 (m, 27H), 5.25 (s, 2H), 5.00-4.95 (m, 12H),
4.70-4.69 (m, 2H), 4.50-4.45 (m, 14H), 4.26 (t, J = 1.6 Hz,
2H), 4.19-4.16 (m, 9H), 3.97-3.90 (m, 14H), 2.86 (t, J = 7.6
(13) Mirkin, M. V.; Bard, A. J. Anal. Chem. 1992, 64, 2293.
(14) Podkoscielny, D.; Hooley, R. J.; Rebek, J., Jr.; Kaifer, A. E. Org.
Lett. 2008, 10, 2865.
J. Org. Chem. Vol. 74, No. 24, 2009 9483

Azagarsamy et al.
JOCArticle
Hz, 2H), 2.15-2.13 (m, 2H) 1.92 (bs, 1H), 1.80-1.20 (m, 159H),
0.90-0.83 (m, 18H); 13C NMR (100 MHz, CDCl3) δ 168.0,
167.8, 160.5, 160.4, 160.2, 159.1, 157.4, 156.1, 147.0, 141.9,
139.7, 139.6, 137.9, 137.8, 135.8, 135.7, 120.4, 119.7, 119.7,
119.3, 110.2, 107.0, 105.7, 105.6, 105.4, 104.8, 104.4, 104.2,
103.5, 101.2, 101.0, 98.2, 82.3, 82.3, 82.1, 82.0, 82.0, 81.1, 70.2,
69.9, 69.0, 68.9, 68.9, 68.1, 66.9, 66.3, 66.2, 65.8, 65.4, 50.0, 32.0,
29.6, 29.4, 29.3, 29.2, 28.1, 26.1, 22.7, 22.0, 14.2; MALDI-TOF
m/z 3143.1 (C185H263FeN3O35 requires 3144.9).
NMR (300 MHz, CDCl3) δ 7.00 (s, 1H), 6.78-6.39 (m, 27H),
5.08 (s, 2H), 5.00-4.91 (m, 12H), 4.68 (s, 2H), 4.49-4.41
(m, 14H), 4.19-4.08 (m, 9H), 3.95-3.85 (m, 14H), 2.65-2.58
(m, 2H), 1.97-1.15 (m, 163H), 0.90-0.78 (m, 18H); 13C NMR
(75 MHz, CDCl3) δ 167.9, 167.9, 167.8, 167.8, 167.7, 160.3,
160.3, 159.0, 159.0, 158.9, 157.3, 157.2, 156.8, 155.9, 146.6,
141.9, 139.4, 139.3, 137.9, 137.6, 135.7, 135.6, 135.4, 120.6
119.5, 119.5, 119.0, 110.1, 110.0, 106.9, 105.7, 105.5, 105.3,
105.2, 104.6, 104.3, 103.3, 101.1, 100.8, 100.8, 82.2, 82.2,
81.9, 81.9, 70.0, 69.7, 68.7, 68.0, 67.9, 67.2, 66.1, 66.0, 65.6,
65.2, 31.7, 29.4, 29.4, 29.2, 29.2, 29.1, 29.0, 28.4, 27.9, 25.9, 25.8,
22.7, 22.5, 21.5, 14.0; MALDI-TOF m/z 3143.6, 3166.5
Synthesis of G3(L4)Fc. According to the general procedure
for click reaction, G3(L4) (0.07 g, 0.011 mmol) was reacted with
azidomethyl ferrocene (8.0 equiv) to yield 0.6 g (83%) of G3-
(L4)Fc. 1H NMR (400 MHz, CDCl3) δ 7.21 (s, 1H), 6.79-6.43
(m, 59H), 5.25 (s, 2H), 5.03-4.95 (m, 28H), 4.70-4.69 (m, 2H),
4.50-4.46 (m, 30H), 4.26 (s, 2H), 4.20-4.17 (m, 7H), 3.97-3.90
(m, 30H), 2.86 (t, J = 7.2 Hz, 2H), 2.15-2.13 (m, 2H) 1.80-1.15
(m, 359H), 0.90-0.83 (m, 42H); 13C NMR (100 MHz, CDCl3) δ
168.0, 168.0, 167.9, 167.9, 160.5, 160.2, 159.2, 159.1, 157.4,
156.1, 147.0, 141.9, 139.6, 137.9, 137.8, 135.8, 135.6, 120.3,
119.8, 119.3, 110.2, 107.0, 105.8, 104.6, 101.2, 101.0, 82.3,
82.1, 82.0, 82.0, 82.0, 81.1, 70.2, 69.9, 69.0, 68.9, 68.9, 68.1,
66.9, 66.3, 66.2, 65.7, 65.5, 49.9, 32.1, 31.9, 29.6, 29.6, 29.4, 29.3,
29.3, 29.2, 29.1, 28.8, 28.1, 26.1, 22.7, 22.2, 14.0; MALDI-TOF
m/z 6610.9 (C393H567FeN3O75 þ Naþ requires 6612.5).
(C185H263FeN3O35 requires 3144.9 and C185H263FeN3O35
þ
Naþ requires 3167.9).
Synthesis of G3(L2)Fc. According to the general procedure
for the formation of triazole, G3(L2) (0.1 g, 0.01 mmol) was
reacted with azidomethyl ferrocene to yield 0.08 g (80%) G3-
(L2)Fc. 1H NMR (300 MHz, CDCl3) δ 7.05 (s, 1H), 6.81-6.40
(m, 59H), 5.12-4.90 (m, 30H), 4.68 (s, 2H), 4.52-4.42 (m, 30H),
4.16-4.07 (m, 9H), 3.98-3.88 (m, 30H), 2.71-2.68 (m, 2H),
2.05-1.15 (m, 361H), 0.86-0.74 (m, 42H); 13C NMR (75 MHz,
CDCl3) δ 167.9, 167.8, 160.3, 159.0, 158.9, 157.3, 156.9, 155.9,
146.6, 141.9, 139.4, 138.0, 137.7, 137.6, 137.5, 135.7, 135.6,
135.4, 120.4, 119.6, 119.0, 110.0, 106.9, 105.6, 105.3, 104.6,
104.4, 103.2, 101.0, 100.8, 82.2, 81.9, 81.9, 81.1, 70.0, 69.7,
68.7, 68.4, 67.9, 67.3, 66.1, 65.6, 65.2, 60.5, 31.7, 29.4, 29.2,
29.2, 29.1, 29.0, 28.5, 27.9, 25.9, 22.5, 14.0; MALDI-TOF m/z
6612.8, 6588.8 (C393H567FeN3O75 þ Naþ requires 6612.5 and
Synthesis of G1(L1)Fc. The alcohol G1(L1) (0.09 g, 0.08
mmol) was subjected to click reaction as per the general proce-
dure to yield 0.10 g (85%) of G1(L1)Fc. H NMR (400 MHz,
1
CDCl3) δ 7.02 (bs, 1H), 6.70-6.39 (m, 11H), 5.08 (bs, 2H), 4.91
(s, 4H), 4.62 (s, 2H), 4.50-4.4 (m, 6H), 4.20-4.09 (m, 9H), 3.88
(t, J = 5.6 Hz, 6H), 2.63 (bs, 2H), 2.42 (bs, 1H), 1.97 (bs, 2H),
1.75-1.70 (m, 4H), 1.50- 1.19 (m, 55H), 0.88-0.84 (t, J = 6.8
Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 167.9, 167.7, 160.3,
159.0, 159.0, 156.9, 155.8, 146.6, 142.1, 139.4, 135.7, 120.7,
118.9, 110.1, 106.8, 105.3, 104.7, 103.3, 101.0, 100.7, 82.1,
81.8, 69.7, 69.1, 67.9, 67.1, 66.0, 65.5, 65.0, 49.6, 31.7, 29.4,
29.4, 29.2, 29.1, 29.0, 28.3, 27.9, 25.8, 22.5, 21.5, 14.0; MALDI-
TOF m/z 1423.3 and 1446.4 (C81H111FeN3O15 requires 1422.6
and C81H111FeN3O15 þ Naþ requires 1446.6).
C
393H567FeN3O75 requires 6589.5).
Synthesis of G3(L3)Fc. According to the general procedure
for click reaction, G3(L3) (0.11 g, 0.018 mmol) was reacted with
1
azidomethyl ferrocene to yield 0.08 g (74%) of G3(L3)Fc. H
NMR (300 MHz, CDCl3) δ 7.01 (s, 1H), 6.79- 6.40 (m, 59H),
5.10 (s, 2H), 5.02-4.88 (m, 28H), 4.68 (s, 2H), 4.50-4.41 (m,
30H), 4.25-4.05 (m, 9H), 3.97-3.84 (m, 30H), 2.68-2.62 (m,
2H), 2.00-1.90 (m, 361H), 0.90-0.75 (m, 42H); 13C NMR (75
MHz, CDCl3) δ 167.9, 167.8, 167.8, 167.7, 160.3, 159.0, 159.0,
158.9, 157.2, 156.9, 155.9, 146.6, 141.8, 139.4, 139.3, 137.8,
137.6, 135.7, 135.6, 135.4, 120.6, 119.6, 119.5, 119.0, 110.0,
106.9, 105.6, 105.2, 104.6, 101.0, 100.8, 82.2, 81.9, 81.2, 70.0,
69.7, 68.7, 67.9, 66.1, 65.6, 31.7, 29.4, 29.4, 29.2, 29.2, 29.1, 29.0,
28.4, 27.9, 25.9, 22.5, 22.5, 14.0; MALDI-TOF m/z 6588.3
(C393H567FeN3O75 requires 6589.5).
Synthesis of G2(L1)Fc. According to the general procedure
for click reaction, G2(L1) (0.3 g, 0.10 mmol) was reacted with
azidomethyl ferrocene to yield 0.31 g (96%) of G2(L1)Fc. H
1
NMR (400 MHz, CDCl3) δ 7.06 (bs, 1H), 6.75-6.35 (m, 27H),
5.12 (s, 2H), 5.00-4.92 (m, 12H), 4.65 (s, 2H), 4.50-4.41 (m,
14H), 4.18-4.08 (m, 9H), 3.92-3.85 (m, 14H), 2.68 (bs, 2H),
2.01-1.10 (m, 163H), 0.90-0.81 (m, 18H); 13C NMR (100
MHz, CDCl3) δ 167.9, 167.8, 160.3, 159.0, 159.0, 157.3, 155.9,
139.4, 137.6, 135.4, 119.6, 110.1, 106.9, 105.6, 105.3, 104.4,
101.1, 100.8, 82.2, 82.0, 81.9, 70.1, 69.8, 68.7, 68.0, 66.2, 65.6,
31.8, 29.5, 29.4, 29.3, 29.2, 29.1, 29.0, 27.9, 25.9, 22.6, 14.0;
MALDI-TOF m/z 3168.5, 3145.6 (C185H263FeN3O35 þ Naþ
requires 3167.9 and C185H263FeN3O35 requires 3144.9).
Synthesis of G3(L1)Fc. As per the general procedure for click
reaction, G3(L1) (0.14 g, 0.02 mmol) was reacted with azido-
methyl ferrocene to yield 0.12 g (80%) of G3(L1)Fc. 1H NMR
(300 MHz, CDCl3) δ 7.08 (s, 1H), 6.80-6.40 (m, 59H), 5.13 (s,
2H), 5.02-4.92 (m, 28H), 4.66 (s, 2H), 4.52-4.42 (m, 30H),
4.22-4.08 (m, 9H), 3.97-3.88 (m, 30H), 2.74-2.68 (m, 2H),
2.08-1.09 (m, 361H), 0.90-0.81 (m, 42H); 13C NMR (75 MHz,
CDCl3) δ 167.9, 167.9, 167.8, 160.3, 159.0, 159.0, 158.9, 157.3,
157.0, 155.9, 146.6, 142.0, 139.4, 137.7, 137.6, 135.8, 135.6,
135.4, 120.4, 119.6, 119.5, 119.0, 110.0, 106.9, 105.6, 105.2,
104.7, 104.4, 103.4, 101.1, 100.8, 82.2, 82.0, 81.9, 81.9, 81.2,
70.1, 69.7, 68.8, 67.9, 67.3, 66.1, 66.0, 65.6, 65.1, 49.6, 31.7, 29.4,
29.2, 29.2, 29.1, 29.0, 28.5, 28.1, 27.9, 25.9, 22.5, 14.0; MALDI-
TOF m/z 6587.0 (C393H567FeN3O75 requires 6589.5).
Conclusion
Differential encapsulation of active functionalities in den-
drimers has been previously studied in the context of gen-
eration dependence. Very little attention has been paid to the
differences in the encapsulation of functional groups within
different layers of dendrimers. We have designed, synthe-
sized, and studied electroactive dendrons to investigate the
possible variations. In our studies, we have shown the
following: (1) We could obtain dendrons where an electro-
active functionality can be incorporated at specific locations
in dendrons. We have utilized the dendrimer sequencing
methods and the versatile 1,3-dipolar cycloaddition (click
reaction) to incorporate the electroactive moiety at different
layers. This chemistry also provides an opportunity to
incorporate any desired functionality at a precise location
in dendrimers. (2) Whereas the redox potential of ferrocene
did not vary with generation, the E1/2 values were signifi-
cantly different in the intermediate layers at higher genera-
tion dendrons. These results suggest that the micro-
environment of the intermediate layers is dictated by the
dendron, while those of the periphery and the core is similar
Synthesis of G2(L2)Fc. According to the general procedure
for the formation of triazole, G2(L2) (0.12 g, 0.04 mmol) was
subjected to click reaction to yield 0.10 g (75%) of G2(L2)Fc. 1H
9484 J. Org. Chem. Vol. 74, No. 24, 2009

Azagarsamy et al.
JOCArticle
to that of the solvent. (3) Although there are thermodynamic
variations, there are no discernible differences in the kinetics
of the heterogeneous electron transfer processes in various
layers of the dendrons. (4) The self-assembled amphiphilic
assembly versions of these dendrons do not exhibit any
CV signals in aqueous solutions. We attribute to this to the
burial of the electroactive functionality in the amphiphilic
assembly, because when studied in a solvent where the
dendron does not self-assemble, the electroactive function-
ality becomes very much accessible. These results suggest
that our amphiphilic dendron assemblies could be used to
provide environment-dependent protection of functional
groups, which could have implications in recognition,
drug delivery, sensing, and separation.
Acknowledgment. We thank NIGMS of the National
Institute of Health DARPA and the Office of Naval Re-
search for partial support.
Supporting Information Available: Experimental details
and spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 74, No. 24, 2009 9485