Effect of guest molecule flexibility in access to dendritic interiors

Article abstract of DOI:10.1021/ol050579b

(Figure Presented) Dendrimers are attractive scaffolds for catalysis, since catalytic sites can be isolated and the catalysts are recoverable and reusable. Herein, we show that conformationally constrained molecules have better access to dendritic cores c

Full text of DOI:10.1021/ol050579b

ORGANIC
LETTERS
2005
Vol. 7, No. 14
2809-2812
Effect of Guest Molecule Flexibility in
Access to Dendritic Interiors
Sivakumar V. Aathimanikandan,† Britto S. Sandanaraj,† Christopher G. Arges,‡
Christopher J. Bardeen,‡,§ and S. Thayumanavan*,†
Department of Chemistry, UniVersity of Massachusetts, Amherst, Massachusetts 01003,
and Department of Chemistry, UniVersity of Illinois, Urbana, Illinois 61801
thai@chem.umass.edu
Received March 16, 2005
ABSTRACT
Dendrimers are attractive scaffolds for catalysis, since catalytic sites can be isolated and the catalysts are recoverable and reusable. Herein,
we show that conformationally constrained molecules have better access to dendritic cores compared to the more flexible counterparts. The
results reported here should have implications in utilizing dendrimers as scaffolds for artificial selectivity in catalysis.
Encapsulation of catalytically active functionalities using
dendrimers has attracted much attention in recent years.1
While the properties of an encapsulated electroactive species
could be elucidated from studying electron-transfer kinetics
and thermodynamics,2 catalytic activity is dependent on the
bimolecular collision efficiency between the encapsulated
species and the substrate. One could reasonably expect that
at higher generations, when the species at the cores of
dendrimers is encapsulated, the dendritic backbones could
act as gatekeepers for substrate access to the catalytic centers.
In fact, this is one of the ways that enzymes maintain high
substrate specificity in nature. While there have been reports
on selectivity in access to dendritic interiors,3 a systematic
investigation on structural factors in substrates that govern
their access to dendritic cores has been lacking. Conventional
wisdom about dendrimers would suggest that the access
would mainly depend on the size of the guest molecules.
However, here we report that conformational flexibility of
the guest molecules plays a significant role in accessibility
to the cores of dendrimers.
We used distance-dependent excited-state quenching through
photoinduced electron transfer as the probe for this study.4
For this purpose, we synthesized benzyl ether dendrons 1-4
and dendrimers 5-8 up to the fourth generation with
anthracene as the fluorescent unit at the focal point and core,
respectively (Figure 1).5 Benzyl ether dendrons were as-
† University of Massachusetts.
‡ University of Illinois.
§ Current address: Department of Chemistry, University of California,
Riverside, CA 92521.
(1) (a) Astruc, D.; Chardac, F. Chem. ReV. 2001, 101, 2991. (b) Oosterom,
G. E.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Angew.
Chem., Int. Ed. 2001, 40, 1828. (c) Crooks, R. M.; Zhao, M.; Sun, L.;
Chechik, V.; Yeung, L. K. Acc. Chem. Res. 2001, 34, 181. (d) Brunner, H.
J. Organomet. Chem. 1995, 500, 39. (e) Seebach, D.; Marti, R. E.;
Hintermann, T. HelV. Chim. Acta 1996, 79, 1710. (f) Enomoto, M.; Aida,
T. J. Am. Chem. Soc. 2002, 124, 6099.
(2) (a) Dandliker, P. J.; Diederich, F.; Gisselbrecht, J. P.; Louati, A.;
Gross, M. Angew. Chem., Int. Ed. Engl. 1995, 34, 2725. (b) Cardona, C.
M.; Mendoza, S.; Kaifer, A. E. Chem. Soc. ReV. 2000, 29, 37. (c) Gorman,
C. B.; Smith, J. C. Acc. Chem. Res. 2001, 34, 60. (d) Gorman, C. B. C. R.
Chimie 2003, 6, 911. (e) Hecht, S.; Fre´chet, J. M. J. Angew. Chem., Int.
Ed. 2001, 40, 74. (f) Stone, D. L.; Smith, D. K.; McGrail, P. T. J. Am.
Chem. Soc. 2002, 124, 856 and references therein.
(3) For examples, see: (a) Diederich, F.; Felber, B. Proc. Natl. Acad.
Sci. U.S.A. 2002, 59, 4778. (b) Niu, Y.; Yeung, L. K.; Crooks, R. M. J.
Am. Chem. Soc. 2001, 123, 6840. (c) Bhyrappa, P.; Young, J. K.; Moore,
J. S.; Suslick, K. S. J. Am. Chem. Soc. 1996, 118, 5708. (d) Kimura, M.;
Shiba, T.; Yamazaki, M.; Hanabusa, K.; Shirai, H.; Kobayashi, N. J. Am.
Chem. Soc. 2001, 123, 5636. (e) Mak, C. C.; Chow, H. F. Macromolecules
1997, 30, 1228.
10.1021/ol050579b CCC: $30.25
© 2005 American Chemical Society
Published on Web 06/03/2005

Figure 1. Structures of anthracene-cored dendrons and dendrimers.
sembled using methods previously reported in the literature.6
The reactive functionality at the focal point of the benzyl
ether dendrons involves a bromomethyl moiety. We at-
tempted the synthesis of 9,10-dihydroxyanthracene to in-
corporate it as the core. However, the poor stability of this
chromophore hampered the isolation of the compounds in
their pure form. Therefore, we converted the functional group
at the focal point of the dendrons from a bromomethyl moiety
to a phenolic moiety by treatment with a monoprotected
phloroglucinol 9, as shown in Scheme 1. Deprotection of
Scheme 1. Synthesis of the Anthracene-Cored Dendrimers
(4) For Stern-Volmer quenching with dendrimers, see: (a) Devadoss,
C.; Bharathi, P.; Moore, J. S. Macromolecules 1998, 31, 8091. (b) Kleinman,
M. H.; Flory, J. H.; Tomalia, D. A.; Turro, N. J. J. Phys. Chem. B 2000,
104, 11472. (c) Pollak, K. W.; Leon, J. W.; Fre´chet, J. M. J.; Maskus, M.;
Abrun˜a, H. D. Chem. Mater. 1998, 10, 30. (d) Pandey, S. Redden, R. A.;
Fletcher, K. A.; Sasaki, D. Y.; Kaifer, A. E.; Baker, G. A. Chem. Commun.
2004, 1318. (e) Vo¨gtle, F.; Plevoets, M.; Nieger, M.; Azzellini, G. C.; Credi,
A.; de Cola, L.; de Marchis, V.; Venturi, M.; Balzani, V. J. Am. Chem.
Soc. 1999, 121, 6290. (f) Kuneida, R.; Fujitsuka, M.; Ito, O.; Ito, M.; Murata,
Y.; Komatsu, K. J. Phys. Chem. B 2002, 106, 7193. (g) Plevoets, M.; Vo¨gtle,
F.; de Cola, L.; Balzani, V. New J. Chem. 1999, 23, 63. (h) Rio, Y.; Accorsi,
G.; Nierengarten, H.; Bourgogne, C.; Strub, J.-M.; Dorsselaer, A. V.;
Armaroli, N.; Nierengarten, J.-F. Tetrahedron 2003, 59, 3833. (i) Murata,
Y.; Ito, M.; Komatsu, K. J. Mater. Chem. 2002, 12, 2009. (j) Matos, M. S.;
Hofkens, J.; Verheijen, W.; De Schryver, F. C.; Hecht, S.; Pollak, K. W.;
Fre´chet, B.; Dehaen, W. Macromolecules 2000, 33, 2967.
the benzoyl moiety followed by treatment with 9-bromo-
methylanthracene (10) or 9,10-bis(bromomethyl)anthracene
(11) afforded the dendrons 1-4 or dendrimers 5-8, respec-
tively.
(5) See Supporting Information for details.
(6) Hawker, C. J.; Fre´chet, J. M. J. J. Am. Chem. Soc. 1990, 112, 7638.
2810
Org. Lett., Vol. 7, No. 14, 2005

Dendritic effects on access to differently sized substrates
were then assessed by measuring the Stern-Volmer ef-
ficiency of various molecules to quench the excited state of
anthracene chromophore. Trialkylamines of different sizes
and shapes were used as molecules that could quench the
fluorescence of anthracene through a photoinduced electron-
transfer process. The excited-state quenchers used in this
study are triethylamine (Et3N), N,N,N′,N′-tetramethyl-
ethylenediamine (TMEDA), N,N,N′,N′,N′′,N′′-hexamethyl-
tris(2-aminoethyl) amine (TREN-Me6), diazabicyclo-
octane (DABCO), and N,N-dimethylaminoadmanatane
(ADM-NMe2).
The fluorescence intensity in the absence (I0) and presence
(I) of a quencher can be related to its concentration ([Q])
using the Stern-Volmer equation: I0/I ) 1 + KSV [Q]. A
plot of I/I0 vs [Q] affords KSV, which is related to the
bimolecular quenching rate constant kq (KSV ) kqτ0, where
τ0 is the fluorescence lifetime of dendrimer in the absence
of quencher). The values of kq for various dendrimer-
quencher combinations are shown in Table 1.7 Note that the
Table 1. Bimolecular Quenching Constants of 1-8 with
Various Alkylamines
Addition of the alkylamine quenchers to compounds 1-8
resulted in a decrease in emission intensity. Fluorescence
intensity decreases upon addition of increasing amounts of
an alkylamine quencher, as exemplified in Figure 2. Redox
Et3N
TMEDA
TREN-Me6
(263 Å3)a
kq × 109
DABCO
(111 Å3)a
kq × 109
M-1 s-1
ADM-NMe2
(193 Å3)a
kq × 109
(122 Å3)a (133 Å3)a
kq × 109
kq × 109
M-1 s-1
M-1 s-1
M-1 s-1
M-1 s-1
1
2
3
4
5
6
7
8
4.3
5.0
4.8
4.4
3.5
3.2
2.9
2.0
4.8
5.0
5.0
4.4
7.4
3.0
2.3
1.7
6.5
6.1
6.7
6.2
8.0
4.5
5.3
2.2
15.6
15.2
11.7
14.1
21.9
11.6
10.8
11.3
9.1
6.7
6.5
7.8
5.2
6.0
5.8
4.9
a Volume was calculated after geometry optimization using MM2.
magnitudes of kq values themselves are quite different from
one quencher to another. This is of little concern to the
dendritic effect, since this magnitude is related to the inherent
redox potential of the trialkylamine.8 This is clearly seen
from the kq value difference for compound 1 with different
amine quenchers. The dendritic effect, on the other hand,
involves relative magnitudes upon increasing generation of
the dendrimer host.
Monodendrons 1-4 exhibited essentially no difference in
quenching efficiency with increase in generation. This
observation is in sharp contrast to the results observed with
the symmetrical dendrimers 5-8, where significant differ-
ences in quenching efficiency were observed with generation.
This observation seems to be consistent with previous reports,
where the unsymmetrical monodendrons retain an open
structure.2f,9 Also note that most of the quenchers had a
decrease in kq between the first- and second-generation
dendrimers 5 and 6, respectively. At early generations,
however, it is too early to label such a decrease as a real
dendritic effect.10 Therefore, we attributed this to simple
steric differences.
Figure 2. (a) Fluorescence spectra of 3 with various concentrations
of the quencher TREN-Me6 in THF/acetonitrile (1:1). (b) Stern-
Volmer plot of the fluorescence spectra shown in panel a.
potentials, excited-state energies, and substituents suggest
that this quenching is due to an intermolecular photoinduced
electron-transfer process and that alternate energy transfer
and heavy-atom-based processes are not viable. To ensure
that the observed quenching is a dynamic process, Stern-
Volmer constants were obtained from steady-state and time-
resolved spectroscopy experiments. We carried out these
experiments side-by-side for compound 8 with TMEDA as
the quencher. In both combinations, the Stern-Volmer
constants obtained from the time-resolved and steady-state
experiments agreed to within 15%, confirming that the
observed fluorescence quenching is a dynamic process
(example shown in Figure 3).
Interesting differences were observed when the quenching
studies were carried out with the symmetrical didendrons
5-8. For example, when triethylamine was used as the
fluorescence quencher, the kq value for the dendrimer 8 was
2.0 compared to the value of 2.9 for dendrimer 7. This change
(7) Experimental error in these measurements is about 5%.
(8) For example, the redox potential of Et3N is 0.96 mV, relative to SCE,
whereas that of DABCO is 0.57 mV. See: Kavarnos, G.; Turro, N. J. Chem.
ReV. 1986, 86, 401.
(9) Cardona, C. M.; Kaifer, A. E. J. Am. Chem. Soc. 1998, 120, 4023.
(10) Dendrimers are thought to undergo a change from an extended
structure to a globular structure between the third and fourth generations.
For example, see: Hawker, C. J.; Wooley, K. L.; Fre´chet, J. M. J. J. Am.
Chem. Soc. 1993, 115, 4375.
Figure 3. Stern-Volmer plots from (a) time-resolved and (b)
steady-state spectroscopic measurements for compound 8 with
quencher TMEDA.
Org. Lett., Vol. 7, No. 14, 2005
2811

in value represents a quenching efficiency decrease of about
31%, which is attributed to the dendritic effect. When
TMEDA was used, the change was about 26%. Therefore,
the quenching efficiency change upon going from the third-
generation dendrimer 7 to the fourth-generation dendrimer
8 is similar within experimental error for both Et3N and
TMEDA. When TREN-Me6 was the quencher, the differ-
ence in quenching efficiency between 7 and 8 was about
59%. This trend is attributed to the bigger size of TREN-
Me6 compared to both Et3N and TMEDA. Since Et3N and
TMEDA are similar in volume, the quenching efficiencies
are about the same.
The most surprising results were obtained when DABCO
was used as the quencher. There was essentially no difference
in quenching efficiency between dendrimers 6-8 with
DABCO as the quencher.11 This is intriguing, because
DABCO is different by only four hydrogen atoms from
TMEDA. One could look at DABCO as the conformationally
constrained version of TMEDA.12 Since it is constrained,
the volume occupied by DABCO is also smaller than
TMEDA. Therefore, the lack of difference in kq between 7
and 8 with DABCO could be attributed to the smaller size
of DABCO. We could not, however, rule out whether
conformational restriction does play a role. To analyze the
possibilities, we looked for a trialkylamine that is bigger in
size but conformationally more restricted than TMEDA. N,N-
Dimethylaminoadamantane (ADM-NMe2) is one of the few
molecules that is synthetically easily accessible and satisfies
the above requirements. ADM-NMe2 occupies a volume
of 192.9 Å3, compared to the volume of 133.1 Å3 for
TMEDA.
Figure 4. Comparison of quenching efficiency of amines in
dendrimers 6-8.
quenching as a probe. We observed that conformationally
restricted molecules could access the dendritic core much
better than flexible ones. This could be due to the difference
in conformational entropy of the amines while passing
through the channels formed by the dendrimer backbone.13
From an applications standpoint, the results could have
implications in catalysis. The demonstration that conforma-
tional freedom of molecules would make a difference in
accessibility to dendritic cores suggests that substrate selec-
tivity could be achieved, where a catalytic center is incor-
porated at the core of a dendrimer and the backbone acts as
a selective gatekeeper. Efforts are underway in our labora-
tories to further understand the fundamental reasons for the
observed differences in accessibility.
The difference in quenching efficiency for dendrimers 7
and 8 with ADM-NMe2 is only 15%, compared to the
difference of 26% observed with TMEDA. This result,
combined with the differences between TMEDA and
DABCO, clearly suggests that conformational freedom of
guest molecules plays a more crucial role in accessing the
interiors of the dendrimers (Figure 4).
Acknowledgment. We are grateful to the National
Science Foundation for a CAREER award (CHE-0353039
to S.T.). Also we acknowledge the Laboratory for Fluores-
cence Dynamics (LFD) at the University of Illinois at
Urbana-Champaign (UIUC) for helping us to carry out the
time-resolved spectral measurements. The LFD is supported
jointly by the Division of Research Resources of the National
Institutes of Health (PHS 5 P41-RRO3155) and UIUC.
In summary, we have studied the access of various
molecules to the cores of dendrimers using fluorescence
(11) Since this was a rather surprising result for us, we repeated the
TMEDA and DABCO experiments with dendrimers 7 and 8 several times.
The values obtained were within the 5% experimental error.
(12) We ran MM2-based energy minimizations on DABCO and TMEDA.
We got several low-energy conformations for TMEDA in which the N1-
N2 through-space distance ranged from 2.8 to 3.8 Å. However, with
DABCO, this distance was always 2.6 Å in as many iterations. See also:
Wong, N. B.; Cheung, Y. S.; Wu, D. Y.; Ren, Y.; Tian, A.; Li W. K. J.
Phys. Chem. A 2000, 104, 6077.
Supporting Information Available: Synthetic and other
experimental details. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL050579B
(13) For an analogy with DNA passing through protein channels, see:
Kong, C. Y.; Muthukumar, M. Electrophoresis 2002, 23, 2697.
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