Redox active, hybrid dendrimers containing Frechet- and Newkome-type blocks

Article abstract of DOI:10.1021/ol0708525

Equation Presented A new series of dendrimers was prepared by covalently attaching a Newkome dendron, a Freenet dendron, and a redox active, aminoferrocene group to a central triazine core. Growth of the Newkome dendron has a more pronounced effect on the

Full text of DOI:10.1021/ol0708525

ORGANIC
LETTERS
2007
Vol. 9, No. 14
2657-2660
Redox Active, Hybrid Dendrimers
Containing Fre´chet- and Newkome-Type
Blocks
Wei Wang, Hao Sun, and Angel E. Kaifer*
Center for Supramolecular Science and Department of Chemistry, UniVersity of Miami,
Coral Gables, Florida 33124-0431
akaifer@miami.edu
Received April 11, 2007
ABSTRACT
A new series of dendrimers was prepared by covalently attaching a Newkome dendron, a Fre´chet dendron, and a redox active, aminoferrocene
group to a central triazine core. Growth of the Newkome dendron has a more pronounced effect on the half-wave potential for the one-electron
oxidation of the ferrocene residue than growth of the Fre´chet dendron. All dendrimers show reversible or quasireversible voltammetric behavior
-
1
at scan rates in the range 0.10−2.0 V s
.
The design of dendrimer macromolecules has advanced
considerably in the past few years. Using the wide diversity
of dendritic architectures developed to date, several groups
have designed, prepared, and characterized dendrimers with
various components in an attempt to endow the resulting
macromolecules with suitable drug encapsulation/delivery,
gene delivery, amphiphilic, and other properties. Some
illustrative examples of this work are the amphiphilic block
codendrimers prepared by Gallani and co-workers,1 the
amphiphilic dendrimers reported by Diederich’s group,2 and
Imae’s amphiphilic surface-block dendrimers,3 among oth-
ers.4 Our work with dendrimers has focused on a general
design based on the attachment of redox,5 fluorescent,6 or
hydrogen bonding7 units to the focal point of AB3 Newkome-
type, ester-terminated dendrons with amide connections
between generational layers. We have also prepared and
(4) (a) Gillies, E. R.; Fre´chet, J. M. J. J. Am. Chem. Soc. 2002, 124,
14137. (b) Yamamoto, K.; Higuchi, M.; Shiki, S.; Tsuruta, M.; Chiba, H.
Nature 2002, 415, 509. (c) Maraval, V.; Laurent, R.; Merino, S.; Caminade,
A. M.; Majoral, J.-P. Eur. J. Org. Chem. 2000, 3555.
(5) (a) Cardona, C. M.; McCarley, T. D.; Kaifer, A. E. J. Org. Chem.
2000, 65, 1857. (b) Ong, W.; Grindstaff, J.; Sobransingh, D.; Toba, R.;
Quintela, J. M.; Peinador, C.; Kaifer, A. E. J. Am. Chem. Soc. 2005, 127,
3353. (c) Sobransingh, D.; Kaifer, A. E. Langmuir 2006, 22, 10540.
(6) (a) Cardona, C. M.; Alvarez, J.; Kaifer, A. E.; McCarley, T. D.;
Pandey, S.; Baker, G. A.; Bonzagni, N. J.; Bright, F. V. J. Am. Chem. Soc.
2000, 122, 6139. (b) Cardona, C. M.; Wilkes, T.; Ong, W.; Kaifer, A. E.;
McCarley, T. D.; Pandey, S.; Baker, G. A.; Kane, M. N.; Baker, S. N.;
Bright, F. V. J. Phys. Chem. B 2002, 106, 8649.
(1) Bury, I.; Donnio, B.; Gallani, J.-L.; Guillon, D. Langmuir 2007, 23,
619.
(2) Guillot, M.; Eisler, S.; Weller, K.; Merkle, H. P.; Gallani, J.-L.;
Diederich, F. Org. Biomol. Chem. 2006, 4, 766.
(3) Ito, M.; Imae, T.; Aoi, K.; Tsutsumiuchi, K.; Noda, H.; Okada, M.
Langmuir 2002, 18, 9757.
(7) Sun, H.; Kaifer, A. E. Org. Lett. 2005, 7, 3845.
10.1021/ol0708525 CCC: $37.00
© 2007 American Chemical Society
Published on Web 06/06/2007

investigated several series of AB2 Fre´chet-type, aromatic
ether dendrimers containing 4,4′-bipyridinium (viologen)
units.5b,8 In this work, we take advantage of the sequential
reactivity of the triazine nucleus to combine in the same
macromolecule (1) a Fre´chet dendron,9 (2) a Newkome
dendron,10 and (3) a redox active residue, such as ferrocene,
leading to novel dendritic frameworks that permit the
convenient fine-tuning of the properties of the redox active
unit. The specific dendrimer structures discussed here are
shown in Figure 1.
Scheme 1. Synthetic Steps for the Preparation of Dendrimer
Fc-TF1N1Ea
a DIPEA ) diisopropylethylamine.
TF3 (43% yield). Reaction of TF1 with Behera’s amine in
acetone (2 days at room temperature) led to the isolation of
the compound TF1N1E (64% yield), which contains first
generation Fre´chet and Newkome dendrons attached to the
triazine core. Again, replacement of Behera’s amine by its
second or third generation analogues would result in the
attachment of the selected amine building block (Newkome
dendrons N2E or N3E) to the triazine core. Finally, treatment
of TF1N1E with aminoferrocene13 in dry refluxing THF
produces in 2 days a reaction mixture from which the redox
active compound Fc-TF1N1E was isolated (61% yield) after
column chromatography.
Figure 1. Structures of the hybrid dendrimers reported in this work.
The naming system describes the building blocks present in each
compound around the triazine nucleus (T): Fc, ferrocenyl; F#,
generation number of the Fre´chet dendron; N#E, ester-terminated
generation number of the Newkome dendron.
1
All new compounds were characterized with H and 13C
The preparation of these dendrimers relies on the dif-
ferential reactivity of trichlorotriazine (cyanuric chloride) in
successive nucleophilic substitution steps. As shown by the
groups of Simanek11 and Wang12 it is possible to direct the
substitution of one, two, or three of the chloro substituents
by controlling the temperature of the reaction. First, we
reacted cyanuric chloride with 3,5-dibenzyloxybenzyl alcohol
(first generation Fre´chet dendron or F1) at 0 °C in THF to
produce the ether TF1 in 53% yield (Scheme 1). Similar
reactions with the second or third generation Fre´chet den-
drons yield the corresponding ethers TF2 (61% yield) and
NMR spectroscopy and either MALDI TOF or FAB mass
spectrometry (see the Supporting Information). The NMR
spectra of all compounds in which at least one amine is
covalently attached to the triazine nucleus shows evidence
for the existence of rotamers.14 This phenomenon has been
described already and results from the partial double bond
character of the covalent bond between the amine nitrogen
and the carbon atom on the triazine core. For instance, at 25
1
°C the H NMR spectrum of Fc-TF1N1E shows three
different signals for the NH proton in the amine connection
between the triazine nucleus and the Newkome dendron, two
different signals for the NH proton connected to the ferrocene
residue, and three signals for the two adjacent protons on
(8) (a) Toba, R.; Quintela, J. M.; Peinador, C.; Roman, E.; Kaifer, A. E.
Chem. Commun. 2001, 857. (b) Toba, R.; Quintela, J. M.; Peinador, C.;
Roman, E.; Kaifer, A. E. Chem. Commun. 2002, 1768.
(9) Hawker, C. J.; Fre´chet, J. M. J. J. Am. Chem. Soc. 1990, 112, 7638.
(10) Newkome, G. R.; Behera, R. K.; Moorefield, C. N.; Baker, G. R.
J. Org. Chem. 1991, 56, 7162.
(11) Steffensen, M. B.; Simanek, E. E. Angew. Chem., Int. Ed. 2004,
43, 5178.
(12) Wang, M.-X.; Yang, H.-B. J. Am. Chem. Soc. 2004, 126, 15412.
(13) Van Leusen, D.; Hessen, B. Organometallics 2001, 20, 224.
(14) (a) Diaz-Ortiz, A.; Elguero, J.; Foces-Foces, C.; De la Hoz, A.;
Moreno, A.; Moreno, S.; Sanchez-Migallon, A.; Valiente, G. Org. Biomol.
Chem. 2003, 1, 4451. (b) Birkett, H. E.; Harris, R. K.; Hodgkinson, P.;
Carr, K.; Charlton, M. H.; Cherryman, J. C.; Chippendale, A. M.; Glover,
R. P. Magn. Reson. Chem. 2000, 38, 504.
2658
Org. Lett., Vol. 9, No. 14, 2007

the cyclopentadienyl ring of ferrocene, which is directly
connected to the triazine nucleus through the -NH- amine
group (Figure 2). The splitting of all these resonances clearly
molecule maintains an approximately constant hydrodynamic
radius in the four solvents surveyed.16 The corresponding
radii (rH) are given in the last row of Table 1 and generally
show the expected trend to increase as larger dendrons are
connected to the triazine core. However, the dendrimer with
the largest molecular weight (Fc-TF2N2E) was found to
have a hydrodynamic radius smaller than that of Fc-
TF3N1E, which suggests that the Newkome dendrons tend
to adopt more collapsed structures around the dendrimer core,
while the Fre´chet dendrons tend to expand out away from
the core.
The electrochemical behavior of these compounds is also
of considerable interest. In the past, we have investigated
the electrochemistry of ferrocenyl residues covalently at-
tached to the Newkome dendrons used in this work.5a In those
dendrimers the ferrocenyl group was directly attached (via
an amide linkage) to the focal point of the Newkome
dendron. In CH2Cl2 solution, the half-wave potentials for
the one-electron oxidation of the ferrocene center were found
to shift to less positive values as the size of the dendron
increased. The displacement of the half-wave potentials is
rationalized as the result of the balance between the polarities
of the bulk solution and that of the inner phase of the
Newkome dendrimers, which is essentially determined by
the amide groups. Thus, dendron growth leads to a more
polar microenvironment for the ferrocene residue, thermo-
dynamically favoring the formation of positive charge, which
is consistent with the observed potential shifts. On the other
hand, Fre´chet dendron growth has a smaller effect on the
redox potentials. For instance, the half-wave potential for
the one-electron reduction of viologen-containing dendrimers
in acetonitrile solution was found to shift moderately to less
negative values with increasing size of the attached Fre´chet
dendrons,8 suggesting that the dendrimer inner phase is less
polar than the bulk solution. Similarly moderate shifts on
the half-wave potential for ferrocene oxidation were observed
by Thayumanavan and co-workers with their unsymmetric
biaryl phenolic dendrimers.17
1
Figure 2. Partial H NMR (400 MHz, DMSO-d6) spectra of Fc-
TF1N1E at variable temeperatures.
reflects the presence of rotamers. Increasing the sample
temperature leads to coalescence of each of these signals
into broad singlets at ca. 55 °C and gradual sharpening of
each of the singlets at higher temperatures (Figure 2).
The diffusion coefficients of the hybrid dendrimers were
measured by using PGSE NMR techniques15 in CDCl3, CD2-
Cl2, CD3CN, and DMSO-d6 solutions (see Table 1). For each
The combination of both types of dendritic building blocks
in the dendrimers surveyed here opens interesting questions
regarding their relative effects on the half-wave potential for
the one-electron oxidation of the ferrocenyl residue. The
recorded voltammetric potential data are given in Table 2.
Table 1. Molecular Weights, Diffusion Coefficients (Do × 106
cm2/s) at 25 °C and Hydrodynamic Radii (rH, nm) of the Hybrid
Dendrimers
In dichloromethane solution the growth of the attached
Newkome dendron has a marked effect on the half-wave
potential, which shifts toward less anodic values. For
instance, the replacement of a first generation by a second
generation Newkome dendron (from Fc-TF1N1E to Fc-
TF1N2E) causes an anodic shift of 54 mV in the half-wave
potential. In comparison to this, the replacement of a first
generation by a third generation Fre´chet dendron (Fc-
TF1N1E to Fc-TF3N1E) has basically no effect on the E1/2
value. In the more polar CH3CN solutions the effect of
dendron replacements on the observed potential values is
FcTF1N1E FcTF1N2E FcTF2N2E FcTF3N1E
M.W.
1012
6.36
8.58
10.8
1.64
0.49
2036
4.71
6.24
7.44
1.12
0.70
2460
4.44
5.79
7.38
1.22
0.73
2285
4.22
5.45
6.37
1.06
0.83
Do(CDCl3)a
Do(CD2Cl2)a
Do(CD3CN)a
Do(DMSO)a
rH (nm)b
a Measured by PGSE NMR techniques in the indicated solvent. b Ob-
tained from Do vs reciprocal solvent viscosity plots.16
of the dendrimers the diffusion coefficient vs reciprocal
solvent viscosity plot is linear, suggesting that each macro-
(16) The Stokes-Einstein equation [Do ) kT/(6πηrH)] was used to obtain
the hydrodynamic radii (rH) from the Do vs η-1 plots.
(17) Jayakumar, K. N.; Bharati, P.; Thayumanavan, S. Org. Lett. 2004,
6, 2547.
(15) Cohen, Y.; Avran, L.; Frish, L. Angew. Chem., Int. Ed. 2005, 44,
520.
Org. Lett., Vol. 9, No. 14, 2007
2659

much less pronounced, because the polarity of the bulk
solution is closer to that of the inner phase of the Newkome
dendrons.5b Increasing the size of the Fre´chet dendrons led
again to minimal changes in the observed potential values.
This is in agreement with some of the diffusion coefficient
data (vide supra) and suggests that the Fre´chet dendrons
expand as wedges away from the core and have little effect
on the microenvironment around the ferrocene center.
Overall, the Newkome dendrons appear to be considerably
more effective than the Fre´chet dendrons at changing the
microenvironment surrounding the redox active ferrocene
residue. This is probably a consequence of their AB3
architectural framework and greater flexibility, which allows
them to wrap around the ferrocene center in a more effective
way.
ficient values previously measured with PGSE NMR tech-
niques, to determine the corresponding standard rate con-
stants (k°) for the heterogeneous electron-transfer processes
in CH2Cl2 solution. The resulting values are given in Table
2. In dichloromethane solution the k° values decrease as the
Table 2. Half-Wave Potentials (E1/2, mV vs Ag/AgCl) and
Standard Rate Constants (103k°, cm s-1) at 25 °C for the
One-Electron Oxidation of the Ferrocene Group in the Hybrid
Dendrimers of Figure 1
FcTF1N1E FcTF1N2E FcTF2N2E FcTF3N1E
E1/2(CH2Cl2)a 372 ( 2
E1/2(CH3CN)a 317 ( 3
318 ( 2
309 ( 3
46 ( 8
335 ( 1
307 ( 1
18 ( 2
376 ( 3
318 ( 1
26 ( 5
k° (CH2Cl2)a
86 ( 15
In the range of scan rates surveyed (0.1-2.0 V s-1) the
voltammetric behavior of all these dendrimers falls in the
reversible to quasireversible range. At scan rates in the lower
end of the range, the behavior is essentially reversible and
the measured peak-to-peak splitting (∆Ep) between the anodic
and the cathodic voltammetric peaks is less than 70 mV for
all these dendrimers. At faster scan rates, the ∆Ep values
increase (see Figure 3), as anticipated for quasireversible
a Data obtained in the indicated solvent also containing 0.2 M tetrabu-
tylammonium hexafluorophosphate.
molecular size of the dendrimer increases, as observed before
in most dendrimers containing a redox active center at their
cores.19 In acetonitrile solution the voltammetric behavior
in all cases was too close to full reversibility and the accurate
determination of the rates of electron transfer was not
possible by Nicholson’s method.
In summary, we have developed a reliable synthetic
methodology to combine a Fre´chet dendron, a Newkome
dendron, and a redox active ferrocene center around a triazine
core. The resulting hybrid molecules constitute the first
reported dendrimers that contain both Fre´chet and Newkome
blocks. In this work we also report the relative effects exerted
by these two important types of dendritic blocks on the
microenvironment of the ferrocene center.
Acknowledgment. We are grateful to the National
Science Foundation for the generous support of this work
(to A.E.K., CHE-0600795). W.W. thanks the University of
Miami for a graduate Maytag fellowship.
Supporting Information Available: Complete synthetic
details and spectroscopic characterization data for all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
Figure 3. Cyclic voltammetric response on glassy carbon (0.071
-
cm2) of a 1.0 mM solution of Fc-TF2N2E in 0.2 M TBA+PF6
/
CH2Cl2. Scan rates: 0.1, 0.2, 0.5, 1.0, and 2.0 V s-1
.
OL0708525
(18) Bard, A. J.; Faulkner, L. R. Electrochemical Methods: Fundamentals
and Applications, 2nd ed.; Wiley: New York, 2001; Chapter 6.
(19) Cameron, C. S.; Gorman, C. B. AdV. Funct. Mater. 2002, 12, 17.
electron-transfer processes. Therefore, Nicholson’s method18
can be employed, in conjunction with the diffusion coef-
2660
Org. Lett., Vol. 9, No. 14, 2007