Design of branched and chiral solvatochromic probes: Toward quantifying polarity gradients in dendritic macromolecules

Article abstract of DOI:10.1021/ol0519902

(Chemical Equation Presented) A pair of chiral, branched monomer building blocks, consisting of a solvatochromic probe and a spectroscopically inactive volume dummy, has been developed. The probe can selectively be excited, and its fluorescence characteristics provide information about local polarity. Incorporation of these monomers into high-generation polyester dendrimers should enable a detailed investigation of the polarity/density profile in dendritic architectures and ultimately allow for the realization of energy gradients from one chromophore building block only.

Full text of DOI:10.1021/ol0519902

ORGANIC
LETTERS
2005
Vol. 7, No. 22
5023-5026
Design of Branched and Chiral
Solvatochromic Probes: Toward
Quantifying Polarity Gradients in
Dendritic Macromolecules
Petar Milosevic and Stefan Hecht*
Max-Planck-Institut fu¨r Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mu¨lheim an
der Ruhr, Germany, and Institut fu¨r Chemie/Organische Chemie, Freie UniVersita¨t
Berlin, Takustr. 3, 14195 Berlin, Germany
hecht@mpi-muelheim.mpg.de
Received August 17, 2005
ABSTRACT
A pair of chiral, branched monomer building blocks, consisting of a solvatochromic probe and a spectroscopically inactive volume dummy,
has been developed. The probe can selectively be excited, and its fluorescence characteristics provide information about local polarity.
Incorporation of these monomers into high-generation polyester dendrimers should enable a detailed investigation of the polarity/density
profile in dendritic architectures and ultimately allow for the realization of energy gradients from one chromophore building block only.
Since the discovery of dendrimers representing a unique class
of perfectly branched macromolecules,1 research interest
shifted toward controlled functionalization of the individual
dendritic compartments. To tune molecular properties, a
better understanding of the complex and dynamic three-
dimensional dendritic structure and its relation to internal
functionalization2 is essential. In particular, the question
concerning the radial density profile of dendrimers, i.e., dense
shell vs dense core,3 raises a long-standing controversy
among researchers in the field.
Our aim is to synthesize dendrimers equipped with
generation-specific solvatochromic probes (Figure 1) and to
elucidate their respective local environment, thereby gaining
information about internal solvation and hence density
distribution throughout the structure.4 Consequently, this
approach should allow the construction of gradient archi-
tectures5 from one monomer building block to realize
(4) The original approach by Schlu¨ter, Rettig, and co-workers is based
on large pyrene-derived building blocks. Thus far only low-generation
dendrons and dendrimers have been synthesized: (a) Modrakowski, C.;
Flores, S. C.; Beinhoff, M.; Schlu¨ter, A. D. Synthesis 2001, 2143-2155.
For pyrene-based probes: (b) Beinhoff, M.; Weigel, W.; Jurczok, M.; Rettig,
W.; Modrakowski, C.; Bru¨dgam, I.; Hartl, H.; Schlu¨ter, A. D. Eur. J. Org.
Chem. 2001, 3819-3829. (c) Weigel, W.; Rettig, W.; Dekhtyar, M.;
Modrakowski, C.; Beinhoff, M.; Schlu¨ter, A. D. J. Phys. Chem. A 2003,
107, 5941-5947. (d) Von Seggern, D.; Modrakowski, C.; Spitz, C.; Schlu¨ter,
A. D.; Menzel, R. Chem. Phys. 2004, 302, 193-202. (e) Beinhoff, M.;
Weigel, W.; Rettig, W.; Bru¨dgam, I.; Hartl, H.; Schlu¨ter, A. D. J. Org.
Chem. 2005, 70, 6583-6591.
(1) (a) Newkome, G. R.; Moorefield, C. N.; Vo¨gtle, F. Dendritic
Molecules: Concepts, Synthesis, PerspectiVes; Wiley-VCH: Weinheim,
2001. (b) Fre´chet, J. M. J.; Tomalia, D. Dendrimers and Other Dendritic
Polymers; Wiley: Chichester, 2001.
(2) Hecht, S. J. Polym. Sci., Part A: Polym. Chem. 2003, 41, 1047-
1058.
(3) Ballauff, M.; Likos, C. N. Angew. Chem., Int. Ed. 2004, 43, 2998-
3020 and references therein.
10.1021/ol0519902 CCC: $30.25
© 2005 American Chemical Society
Published on Web 09/28/2005

results were obtained using the pair of a p-aminobenzoate
probe and a p-imidobenzoate dummy (Scheme 1). Our idea
Scheme 1. Concept and Synthesis of Model Compounds
Figure 1. Investigating conformational dynamics in dendrimers
by utilizing generation-specific solvatochromic probes. Dendrimer
series consisting of generations entirely labeled with probes (top)
or exact regioisomers containing a single generation-specific probe
(bottom) are targeted. Probes are shown in red.
is based on replacing the amino donor group in model probe
1 with an imido acceptor unit in model dummy 2, thereby
rendering the dummy optically inactive yet conserving
chemical connectivity and structure.
vectorial energy and electron-transfer processes, essential to
efficient light harvesting and charge separation, respectively.6
An alternative approach to probe each internal dendritic layer
has recently been reported by Thayumanavan and co-
workers, who measured the accessibility of generation-
specific anthracene probes within convergently grown Fre´chet-
type dendrons7 by fluorescence quenching using a small
molecule quencher.8
The absorption spectra of the model probe/dummy pair
show both required features: (1) selective excitation of 1
due to batho- and hyperchromically shifted absorption
maxima (as compared to 2) rather independent of solvent
and (2) strong solvatochromic response of 1 (Figure 2). The
Here, we disclose both synthesis and photophysical
properties of a pair of chiral, branched monomer building
blocks, one of them serving as solvatochromic probe and
the other as volume dummy, i.e., closely resembling the
probe’s structure yet being spectroscopically inactive. The
described monomers should allow for the synthesis of high-
generation dendrimers since the compact chromophore is
directly incorporated, not appended,4,8 into the structure at a
given branch point.
The probe has to fulfill several key requirements: it should
be a compact and branched chromophore, which can be
selectively excited in the presence (of a large excess) of the
dummy and thereby exhibits significantly altered emission
response toward a changing environment (solvatochromicity).
Large solvatochromicity can be realized in donor-acceptor
systems that display dual fluorescence from locally excited
(LE) as well as twisted intramolecular charge transfer (TICT)
states.9 In higher generation dendrimers the emission char-
acteristics might in addition be influenced by steric effects
due to the reorganization accompanying TICT state forma-
tion.
Figure 2. Absorption and emission spectra of model compounds.
Probe 1 in cyclohexane: absorption (solid red line), emission
(dashed red line). Probe 1 in acetonitrile: absorption (solid blue
line), emission (dashed blue line). Absorption of dummy 2 in
cyclohexane (green line) and acetonitrile (black line). All spectra
at 25 °C; for emission spectra λexc ) 315 nm was used.
Although different probe/dummy model systems have been
prepared and spectroscopically studied, the most promising
strong solvatochromicity of the probe 1 is most likely the
result of vastly different solvation along the 1La excited-state
surface leading to emission from either the LE state in the
case of nonpolar solvents (cyclohexane) or the TICT state
in the case of polar solvents (acetonitrile).9
To further test the suitability of this system, a 1:44 mixture
of 1 and 2 resembling the relative ratio of both components
in a G-4 dendrimer carrying a single probe unit (Figure 1,
bottom) was investigated. In this “pseudo G-4 scenario”,
selective excitation of 1 could be achieved at λexc ) 315 nm
(5) A unique example of a gradient architecture is given by: Devadoss,
C.; Bharathi, P.; Moore, J. S. J. Am. Chem. Soc. 1996, 118, 9635-9644.
(6) Adronov, A.; Fre´chet, J. M. J. Chem. Commun. 2000, 1701-1710.
(7) Grayson, S. M.; Fre´chet, J. M. J. Chem. ReV. 2001, 101, 3819-
3867.
(8) Sivanandan, K.; Aathimanikandan, S. V.; Arges, C. G.; Bardeen, C.
J.; Thayumanavan, S. J. Am. Chem. Soc. 2005, 127, 2020-2021.
(9) (a) Grabowski, Z. R.; Rotkiewicz, K.; Rettig, W. Chem. ReV. 2003,
103, 3899-4031. (b) Rettig, W. Angew. Chem., Int. Ed. Engl. 1986, 25,
971-988.
5024
Org. Lett., Vol. 7, No. 22, 2005

Scheme 2. Synthesis of Dendritic Dummy/Probe Monomers
Figure 3. Absorption and emission spectra of the probe/dummy
model pair in 1:44 ratio resembling a G-4 dendrimer as depicted
in the bottom of Figure 1. Absorption at 25 °C in cyclohexane (solid
red line) and acetonitrile (solid blue line). Emission at 25 °C in
cyclohexane (dashed red line) and acetonitrile (dashed blue line)
using λexc ) 315 nm.
and the probe exhibited strongly solvent-dependent fluores-
cence emission featuring a large bathochromic shift (∆λabs
) 105 nm) and a somewhat decreased intensity when
comparing cyclohexane with acetonitrile solutions (Figure
3). A separate experiment analyzing the individual contribu-
tions in the mixture is provided in Supporting Information.
On the basis of these encouraging results, we engaged in
the synthesis of the dendritic probe and dummy monomers.
To enable efficient and modular dendrimer growth allowing
for generation-specific labeling, convergent polyesters pre-
pared from acid-diol-type AB2 monomers were targeted.9,10
While a benzoic acid functionality was already present, a
tartrate-based building block was utilized to incorporate the
diol unit into the monomers. In addition to providing both
hydroxyl groups necessary for branching multiplicity, the
tartrate also introduces chirality into the system and the
resulting dendrimers.11
The convergent synthesis of both monomers involved
preparation of benzyl-protected tartrate-based building blocks,
which were joined with the respective p-substituted benzoate
moieties (Scheme 2). Whereas the dummy precursor 8 was
prepared in good yields via imide formation between bis-
benzylated tartaric acid anhydride 4 and benzyl 4-aminoben-
zoate 6 utilizing chemistry pioneered by Vorbru¨ggen,12 the
probe precursor 9 was accessed in rather sluggish yields by
Cu-catalyzed amination13 of 4-iodobenzoate 7 with bis-
benzylated pyrrolidine 5. Initially anticipated direct conver-
sion 8 f 9 by chemoselective reduction14 was not successful.
The fully benzylated precursors 8 and 9 were converted into
the respective monomers 10 and 11 via complete hydro-
genolysis followed by chemoselective rebenzylation of the
focal carboxylates.
To verify the key optical requirements of the synthesized
probe and dummy monomers, their absorption and emission
characteristics in various solvents were investigated in a
similar fashion as described for the model system (Figure
4). While the dummy 10 was not affected as compared to
the model 2, the probe’s (11) absorption and emission
characteristics were somewhat altered upon introduction of
the cyclic constraint, i.e., diethylamino group f pyrrolidino
group, as compared to model 1. Both the large Stoke’s shift
of the emission arising from the LE state was diminished,
i.e., ∆λmax ) 22 nm for 11 instead of ∆λmax ) 45 nm for 1
in chloroform, and the emission was less dramatically altered
in response to changing solvent. Compared to model 1, the
emission shifted hypsochromically in cyclohexane (λem
)
(10) Efficient convergent synthesis of high-generation polyester den-
drimers based on 2,2-bis(hydroxymethyl)propionic acid has been reported
in: (a) Ihre, H.; Hult, A.; Soederlind, E. J. Am. Chem. Soc. 1996, 118,
6388-6395. (b) Ihre, H.; Hult, A.; Fre´chet, J. M. J. Macromolecules 1998,
31, 4061-4068.
(11) For a review on chiral dendrimers, consult: Ramagnoli, B.; Hayes,
W. J. Mater. Chem. 2002, 12, 767-799 and references therein.
(12) Vorbru¨ggen, H. Acc. Chem. Res. 1995, 28, 509-520.
(13) For a review, consult: Ley, S. V.; Thomas, A. W. Angew. Chem.,
Int. Ed. 2003, 42, 5400-5449 and references therein.
330 nm) and showed two emission bands in acetonitrile (λem
) 347 and 485 nm). This suggests that rigidification of the
donor moiety in 11 leads to dual fluorescence emission from
both LE and TICT states.9
(14) Merkel, W.; Mania, D.; Bormann, D. Liebigs Ann. Chem. 1979,
461-468.
Org. Lett., Vol. 7, No. 22, 2005
5025

probe monomer 11 displays a significant solvatochromic
response of its emission characteristics (Figure 5). Increasing
solvent polarity seems to stabilize the TICT state relative to
the LE state, and dual fluorescence can be observed. Both
emission maxima and relative intensities seem to correlate
well with solvent polarity, in particular with Reichardt’s
solvent parameter ET(30)15 (Table 1). In addition to solvent
Table 1. Solvatochromic Response of Probe Monomer 11
solvent
C6H12
CH2Cl2
CH3CN
CH3OH
λmaxLE (nm)
λmaxTICT (nm)
Irel(LE)c
Irel(TICT)c
ET(30)d
330
noa
1
noa
31.2
344
439b
0.56
1
347
359
484b
0.17
0.58
45.6
488b
0.05
0.07
55.4
Figure 4. Absorption and emission spectra of branched probe and
dummy monomers. Probe 11 in cyclohexane: absorption (solid red
line), emission (dashed red line). Probe 11 in acetonitrile: absorp-
tion (solid blue line), emission (dashed blue line). Absorption of
dummy 10 in cyclohexane (green line) and acetonitrile (black line).
All spectra at 25 °C; for emission spectra λexc ) 315 nm was used.
40.7
a Not observed. b Broad maximum. c Relative intensity. d Reichardt’s
solvent parameter.15
polarity, solvent acidity seems to contribute to the observed
effects, as illustrated by the use of methanol.
Monomers 10 and 11 still exhibit the necessary require-
ments for successful design of dendrimers carrying genera-
tion-specific probes. Selective excitation can be achieved and
In conclusion, we have synthesized a pair of sterically
similar, yet optically contrasting, branched chiral monomers,
i.e., dummy 10 and probe 11. These building blocks should
enable the preparation of high-generation, convergent poly-
ester dendrimers equipped with single or multiple generation-
specific solvatochromic probes (see Figure 1) and thereby
allow for a quantitative evaluation of the internal solvation
profile. In addition to providing valuable insight into the
density distribution throughout dendritic architectures, the
building blocks described herein should facilitate the design
of gradient systems based on one monomer unit only.
Furthermore, the effect of chirality on these parameters can
conveniently be studied.
Acknowledgment. Generous support by the Sofja Kova-
levskaja Award of the Alexander von Humboldt Foundation,
endowed by the Federal Ministry of Education and Research
(BMBF) within the Program for Investment in the Future
(ZIP) of the German Government, is gratefully acknowl-
edged.
Supporting Information Available: Description of all
experimental procedures including synthesis, characterization
data, and additional optical spectra. This material is available
free of charge via the Internet at http://pubs.acs.org.
Figure 5. Emission spectra of branched probe monomer in various
solvents. Probe 11 in cyclohexane (red line), acetonitrile (blue line),
methylene chloride (green line), and methanol (black line). All
spectra at 25 °C with λexc ) 315 nm.
OL0519902
emission from the dummy monomer 10 is negligible at λexc
) 315 nm (see Supporting Information). Furthermore, the
(15) Reichardt, C. SolVent and SolVent Effects in Organic Chemistry,
2nd ed.; VCH: Weinheim, 1988.
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Org. Lett., Vol. 7, No. 22, 2005