Self-assembly of a copper-ligating dendrimer that provides a new non- heme metalloprotein mimic: 'Dendrimer effects' on stability of the bis(μ- oxo)dicopper(III) core [10]

Full text of DOI:10.1021/ja982282x

874
J. Am. Chem. Soc. 1999, 121, 874-875
Self-Assembly of a Copper-Ligating Dendrimer that
Provides a New Non-Heme Metalloprotein Mimic:
“Dendrimer Effects” on Stability of the
Bis(µ-oxo)dicopper(III) Core
Masashi Enomoto and Takuzo Aida*
Department of Chemistry and Biotechnology
Graduate School of Engineering, The UniVersity of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
ReceiVed June 30, 1998
ReVised Manuscript ReceiVed December 8, 1998
Dendrimers are nanosized hyperbranched macromolecules with
well-defined three-dimensional shapes, which are expected to
serve as building blocks for the construction of organized
functional materials.1 Recently, self-assembly of dendrimers to
generate well-defined nanoscale architectures have been inves-
tigated by utilization of van der Waals, hydrophobic, hydrogen-
bonding, metal-ligating, and electrostatic interactions,2,3 which
play important roles in biological supramolecular assemblies.
However, examples of self-asembled dendrimers which exhibit
bio-related functions have been very limited to date. Herein we
report the first example of a dendritic non-heme metalloprotein
mimic by O2-driven self-assembly of a copper-ligating dendrimer
and wish to highlight a clear “dendrimer effect” on stability of
the focal point bis(µ-oxo)dicopper species toward oxidative self-
decomposition. Bis(µ-oxo)-bridged bimetallic complexes have
attracted a great deal of attention as synthetic models of active
sites of multinuclear metalloproteins such as methane monooxy-
genase and ribonucleotide reductase.4 As an example, Tolman et
al. have reported that Cu(I) complexes of N-substituted 1,4,7-
triazacyclononanes such as [Bn3TACNCu(MeCN)]PF6 (1b; Bn
) benzyl [Chart 1]) react with O2 to form [(Bn3TACNCu)2(µ-
O)2]2+ (1c).5 However, 1c is thermally unstable with a half-life
of only 7 s at -10 °C because of an oxidative self-decomposition
at the N-Bn bonds.
Figure 1. Reaction of [Ln3TACNCu(MeCN)]PF6 (2b-4b; 2.4 mM) with
O2 in CH2Cl2 at -78 °C; second-order rate constants (k2) for the formation
of [(Ln3TACNCu)2(µ-O)2](PF6)2 (2c-4c). Inset: UV-vis spectral change
at -78 °C of a CH2Cl2 solution (2.4 mM, 1-mm path quartz cell) of 3b
after bubbling with dry O2. Absorption of the dendron subunits at 280
nm is subtracted.
(Chart 1), in which the products displayed characteristic TACN
signals in the 1H and 13C NMR spectra,8 in agreement with those
reported for [Bn3TACNCu(MeCN)]PF6 (1b).5a
Reaction of [Ln3TACNCu(MeCN)]PF6 (b) with O2 was found
to be highly dependent on the size of the dendron subunits. Upon
bubbling of a CH2Cl2 solution of 3b (2.4 mM) with O2 at -78
°C, the color of the solution gradually turned from pale purple to
deep orange-brown, and displayed growth of two intense absorp-
tion bands (302 and 411 nm) in the UV-vis spectrum (Figure 1,
inset), characteristic of bis(µ-oxo)dicopper(III) species.5 Reso-
nance Raman spectroscopy of the reaction mixture at -78 °C9
clearly showed an absorption band at 600 cm-1 assignable to the
[Cu2(µ-O)2]2+ core, which shifted to 569 cm-1 when 18O2 was
used in place of 16O2. Since the observed isotope shift of 31 cm-1
agrees well with those reported for [Cu2(µ-O)2]2+ complexes,10
the reaction product is unambiguously [(L33TACNCu)2(µ-O)2]-
(PF6)2 (3c). In accord with the bimolecular reaction mechanism
(Chart 1), the spectral change profile, thus observed in Figure 1
(inset), indicated that the oxygenation obeys a second-order
kinetics for 3b with a rate constant (k2) of 1.3 × 10-2 M-1 s-1
(Figure 1).8 Likewise, the reaction of 2b with O2, under conditions
identical to those of the above, also obeyed a second-order
A series of triamine-core aryl ether dendrimers (Ln3TACN, n
[number of the aromatic layers of the dendron subunits] ) 2 (2a),
3 (3a), and 4 (4a); Chart 1) was synthesized by alkaline-mediated
coupling6 of the corresponding dendron chlorides7 with 1,4,7-
1
triazacyclononane (TACN) and characterized by means of H
NMR, MALDI-TOF-MS, and elemental analysis.8 The diamag-
netic Cu(I) complexes ([Ln3TACNCu(MeCN)]PF6, n ) 2 (2b),
3 (3b), 4 (4b)) were prepared by the reaction of 2a-4a (12 mM)
with [Cu(MeCN)4]PF6 (12 mM) in CH2Cl2 under argon at 20 °C
(1) (a) Tomalia, D. A. AdV. Mater. 1994, 6, 529. (b) Fre´chet, J. M. J. Science
1994, 263, 1710. (c) Newkome, G. R.; Moorefield, C. N.; Vo¨gtle, F. Dendritic
Macromolecules: Concepts, Synthesis, PerspectiVes; VCH: Weinheim,
Germany, 1996.
(2) (a) Zimmerman, S. C.; Zeng, Reichert, D. E. C.; Lolotuchin, S. V.
Science 1996, 271, 1095. (b) Balagurusamy, V. S. K.; Ungar, G.; Percec, V.;
Johansson, G. J. Am. Chem. Soc. 1997, 119, 1539. (c) Hudson, S. D.; Jung,
H.-T.; Percec, V.; Cho, W.-D.; Johansson, G.; Ungar, G.; Balagurusamy, V.
S. K. Science 1997, 278, 449. (d) Huck, W. T. S.; van Veggel, F. C. J. M.;
Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl. 1996, 35, 1213. (e) Huck, W.
T. S.; Hulst, R.; Timmerman, P.; van Veggel, F. C. J. M.; Reinhoudt, D. N.
Angew. Chem., Int. Ed. Engl. 1997, 36, 1006. (f) Gitsov, I.; Fre´chet, J. M. J.
J. Am. Chem. Soc. 1996, 118, 3785. (g) Newkome, G. R.; Guther, R.;
Moorefield, C. N.; Cardullo, F.; Echegoyen, L.; Perezcordero, E.; Luftmann,
H. Angew. Chem., Int. Ed. Engl. 1995, 34, 2023. (h) Chow, H. F.; Chan, I. Y.
K.; Chan, D. T. W.; Kwok, R. W. M. Chem. Eur. J. 1996, 2, 1085. (i) Tomioka,
N.; Takasu, D.; Takahashi, T.; Aida, T. Angew. Chem., Int. Ed. 1998, 37,
1531.
kinetics, where the observed rate constant (k2 ) 1.39 M-1 s-1
)
was two-orders of magnitude larger than that for 3b. In sharp
contrast, the largest 4b showed virtually no spectral change
throughout the observation for 16 h at -78 °C. Thus, the copper-
ligating aryl ether dendrimers [Ln3TACNCu(MeCN)]PF6, upon
reaction with O2, assemble to form [(Ln3TACNCu)2(µ-O)2](PF6)2,
(6) Beissel, T.; Della Vedova, B. S. P. C.; Wieghardt, K.; Boese, R. Inorg.
Chem. 1990, 29, 1736.
(7) (a) Balagurusamy, V. S. K.; Ungar, G.; Percec, V.; Johansson, G. J.
Am. Chem. Soc. 1997, 119, 1539. (b) Hawker, C. J.; Fre´chet, J. M. J. J. Am.
Chem. Soc. 1990, 112, 7638.
(8) See Supporting Information.
(9) Excitation wavelength ) 488 nm.
(10) (a) Mahapatra, S.; Halfen, J. A.; Wilkinson, E. C.; Pan, G.; Wang,
X.; Young, V. G., Jr.; Cramer, C. J.; Que, L., Jr.; Tolman, W. B. J. Am.
Chem. Soc. 1996, 118, 11555. (b) Mahadevan, V.; Hou, Z.; Cole, A. P.; Root,
D. E.; Lal, T. K.; Solomon, E. I.; Stack, T. D. P. J. Am. Chem. Soc. 1997,
119, 11996.
(3) Zeng, F.; Zimmerman, S. C. Chem. ReV. 1997, 97, 1681 and references
therein.
(4) (a) Que, L., Jr.; Dong, Y. Acc. Chem. Res. 1996, 29, 190. (b) Wallar,
B. J.; Lipscomb, J. D. Chem. ReV. 1996, 96, 2625 and references therein. (c)
Kitajima, N.; Moro-oka, Y. Chem. ReV. 1994, 94, 735 and references therein.
(5) (a) Mahapatra, S.; Halfen, J. A.; Tolman, W. B. J. Am. Chem. Soc.
1996, 118, 11575. (b) Halfen, J. A.; Mahapatra, S.; Wilkinson, E. C.; Kaderli,
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10.1021/ja982282x CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/14/1999

Communications to the Editor
J. Am. Chem. Soc., Vol. 121, No. 4, 1999 875
Chart 1. Schematic Representations of the Structures of
Triamine-Core Dendrimers (Ln3TACN, 1a-4a) and
Self-Assembly of Their Cu(I) Complexes by the Reaction with
O2
Figure 2. Oxidative decomposition of [(Ln3TACNCu)2(µ-O)2](PF6)2
(1c-3c) in CH2Cl2: (A) Half-lives at -10 °C (2.4 mM) and (B) kinetic
parameters. The half-life of [(Bn3TACNCu)2(µ-O)2]2+ (1c) is taken from
ref 5a.
nondendritic 1c (13.6), indicating that the active centers of these
three bis(µ-oxo)dicopper complexes are almost comparable to one
another. On the other hand, quite interestingly, the entropies of
activation (∆S‡, eu) are highly dependent on the size of the
dendron subunits: 3c in the decomposition showed the most
negative ∆S‡ (-9.3) among the three complexes, while the ∆S‡
for 2c (-5.6) was only a little more negative than that for 1c
(-4.8).12 Therefore, the apparent stability of 3c toward oxidative
decomposition is given by the large entropy loss required for the
reaction. Namely, the intra-complex oxidative decomposition
requires access of the N-benzyl moieties at the dendron focal
points to the bis(µ-oxo)dicopper active center. In the case of 3c,
it is likely that the large six dendron subunits are so densely
packed that the focal point TACN ligands may be conformation-
ally frozen in such a way that the N-C (dendron) bonds are
pointing away from the active center. On the other hand, the
dendron subunits in 2c are not large enough to affect the
conformational motion of the TACN ligands. Thus, this is the
first example of highly robust non-heme metalloprotein mimic
by supramolecular interaction.
Much effort has been made to design bis(µ-oxo)-bridged
bimetallic complexes which are thermally robust but exhibit
relevant reactivities for oxygenation.4 The present study with
dendritic ligands provides a new synthetic approach to non-heme
metalloproteins, where the susceptibility to the oxidative self-
decomposition is considerably reduced by the steric interaction
among the self-assembled dendrimer subunits that surround the
active site. Utilization of other oxophilic transition metals for this
reaction is one of the subjects worthy of further investigation.
where the dendron subunits obviously affects the accessibility of
the two copper cores to form the di-µ-oxo bridge.
More interestingly, the dendron subunits also have a great
influence on the apparent stability of the resulting complexes
toward oxidative decomposition. On warming a CH2Cl2 solution
of 3c from -78 to -10 °C, the characteristic UV-vis absorption
bands started to decay with time8 and completely disappeared in
24 000 sec, indicating the occurrence of an oxidative decomposi-
1
tion of the [Cu2(µ-O)2]2+ core. MALDI-TOF-MS and H NMR
analyses of the reaction mixture, after treatment with aqueous
NH3, showed that the decomposition is accompanied by an
oxidative cleavage of the N-C (dendron) bonds to give partially
dealkylated TACNs and a formyl-ended L3-dendron.8 From the
absorption spectral change profile, the decomposition was found
to obey a first-order kinetics,8 indicating that 3c decomposes in
an intra-complex fashion. Here, it is also interesting to note that
the half-life of 3c at -10 °C was evaluated to be 3075 s (Figure
2A), which is considerably longer than the reported half-life of 7
s for nondendritic [(Bn3TACNCu)2(µ-O)2]2+ (1c) under similar
conditions.5 Even at higher temperatures such as 0 and 20 °C,
the half-lives were as long as 925 and 77 s, respectively.
Compared with 3c, one-generation smaller 2c decomposed much
faster at -10 °C, where the half-life was only 24 s. Thus, a
discrete gap in stability is present between 2c and 3c. The
temperature dependence of the rate constant of decomposition
gave kinetic parameters,8,11 which are compared with those
observed for the oxidative decomposition of nondendritic 1c12
(Figure 2B): The enthalpies of activation (∆H‡, kcal mol-1) of
2c (14.3) and 3c (14.8) are not much different from that of
Acknowledgment. The authors are grateful to Professor V. Percec
of Case Western Reserve University for generous instruction for the
preparation of dendron chlorides, to Dr. Y. Ohkubo of JASCO Corporation
for resonance Raman spectroscopy, and to Professor T. Kitayama and
Mr. T. Hirano of Osaka University for 125-MHz 13C NMR spectroscopy.
Supporting Information Available: Details for synthetic procedures
and spectroscopic data for Ln3TACN (1a-4a), [Ln3TACNCu(MeCN)]-
PF6 (1b-4b), and [(Ln3TACNCu)2(µ-O)2](PF6)2 (1c-3c), kinetic mea-
surements for formation and decomposition of 1c-3c, product analyses
for decomposition of 2c and 3c, resonance Raman spectra of 3c (16O2,
18O2) (PDF). This material is available free of charge via the Internet at
http://pubs.acs.org.
JA982282X
(12) The kinetic parameters (∆H‡ and ∆S‡) for 1c were obtained on the
basis of the rate constants of decomposition at 212-243 K, which are in
excellent agreement with those reported in ref 5a.
(11) Calculated on the basis of the rate constants of decomposition observed
at 242-263 K for 2c and 263-293 K for 3c.