Nucleobase dendrimer as a multidentate ligand for a rate-earth metal ion

Article abstract of DOI:10.1039/b000318m

Novel dendritic macromolecules consisting of uracil units (LnU-OBn) with the numbers of the nucleobase layers (n) of 2-4 were synthesized; L3U-OBn and L4U-OBn both formed 1:1 complexes with La³⁺, where the L4U-OBn-La³⁺ complex, in pa

Full text of DOI:10.1039/b000318m

Nucleobase dendrimer as a multidentate ligand for a rare-earth metal ion
Masahide Tominaga, Jun Hosogi, Katsuaki Konishi* and Takuzo Aida*
Fields and Reactions, Precursory Research for Embryonic Science and Technology, Japan Science and Technology
Corporation, and Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of
Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. E-mail: aida@macro.t.u-tokyo.ac.jp
Received (in Cambridge, UK) 5th January 2000, Accepted 15th March 2000
Novel dendritic macromolecules consisting of uracil units
(LnU-OBn) with the numbers of the nucleobase layers (n) of
2–4 were synthesized; L3U-OBn and L4U-OBn both formed
1+1 complexes with La3+, where the L4U-OBn–La3+ com-
plex, in particular, was highly robust towards methanol-
ysis.
the electronic absorption spectra in MeCN, LnU-OBn (n =
2–4) showed an absorption band due to the uracil units at
274.8–275.6 nm, which is red-shifted from that of non-dendritic
L1U-OBn (270.0 nm), indicating some intramolecular elec-
tronic interactions among the dendritic uracil units.
Dendritic polyuracils bear many heteroatoms and are ex-
pected to show potential for trapping of multi-coordinate metal
ions. La3+ was chosen as a substrate, which is characterized by
the largest ionic radius among rare-earth metal ions, and its
preference to adopt a high coordination number (up to 12).9
Typically, upon titration of an MeCN solution of L3U-OBn
(10 mM) with La(OTf)3 at 25 °C, the absorption band of the
uracil units red-shifted from 275.2 to 281.4 nm with clear
isosbestic points at 248.4 and 275.0 nm (Fig. 2, inset). Plots of
the absorbance at 296.6 nm vs. [La(OTf)3]0 showed a clear
inflection point at a mole ratio [L3U-OBn]0/[La(OTf)3]0 of
unity (Fig. 2). Job plots of DA at 296.6 nm also exhibited a
maximum at a mole ratio [L3U-OBn]0/[La(OTf)3]0 of unity.
Furthermore, MALDI-TOF-MS spectrometry of a mixture of
L3U-OBn and La(OTf)3 (1+2) showed a peak at 2133 due to
[L3U-OBn–La(OTf)2]+ (calc. m/z 2134) in addition to that of a
Na+ adduct [Fig. 1(a) (ii)]. These observations indicate a strong
one-to-one complexation between L3U-OBn and La3+ with an
Dendrimers are hyperbranched, three-dimensional macromole-
cules with a pseudo network structure,1 and have a potential for
trapping of guest molecules.2 In particular, dendritic molecules
bearing binding sites for metal ions have attracted great
attention.3–5 Herein, we report the synthesis of the first dendritic
polynucleobase, and highlight its very high activity for
multidentate ligation with lanthanum ion.6
For the synthesis of the dendritic architecture, we chose uracil
as a building block. Synthesis of the dendritic polyuracils (LnU-
OBn; n = number of the nucleobase layers) was carried out by
the convergent approach (Scheme 1) starting from (i) bromina-
tion of 1,3-dibenzyl-5-benzyloxymethyluracil (L1U-OBn) with
HBr–AcOH,7 followed by (ii) an alkaline-mediated coupling
reaction of the resulting 5-bromomethyl derivative (L1U-Br)
with 5-benzyloxymethyluracil 1, to give L2U-OBn. Repetition
of these two steps allowed formation of higher-generation LnU-
OBn (n = 3, 4).8 The absence of structural defects in LnU-OBn
(n = 2–4) was confirmed by 1H NMR, MALDI-TOF-MS and
SEC analyses. For example, LnU-OBn (n = 2–4) all showed a
single MALDI-TOF-MS peak due to [M + Na]+ [Fig. 1(a) (I)–
(III)] and a unimodal SEC chromatogram [Fig. 1(b)]. LnU-OBn
(n = 2–4) were highly soluble in common organic solvents such
as CH2Cl2, CHCl3, benzene, acetone, MeCN and DMF, but
scarcely soluble in protic solvents such as MeOH and water. In
association constant > 107 M21 10
Likewise, titration of one-
.
generation larger L4U-OBn with La(OTf)3 (Fig. 2) showed a
similar red shift (275.6 to 281.0 nm) with two isosbestic points
(246.8, 271.8 nm), and a Job plot again indicated a 1+1
complexation of L4U-OBn with La3+. Furthermore, a MALDI-
TOF-MS peak due to the one-to-one adduct [L4U-OBn–
La(OTf)2]+ (calc. m/z 3847) was observed [Fig. 1(a) (iii)].
An MeCN solution of L3U-OBn (2.5 mM) at 25 °C showed
two CNO stretching vibrational bands at 1708 [C(2)NO] and
1665 cm21 [C(4)NO] [Fig. 3(a)].11 On the other hand, when
La(OTf)3 (5.0 mM) was added to the solution, a new IR band at
1609 cm21, assignable to the coordinated CNO functionality,
Fig. 1 (a) MALDI-TOF-MS spectra of (I) L2U-OBn, (II) L3U-OBn, (III)
L4U-OBn, (ii) a 1+2 mixture of L3U-OBn and La(OTf)3 and (iii) a 1+2
mixture of L4U-OBn and La(OTf)3. (b) SEC profiles of dendritic
polyuracils LnU-OBn (n = 2–4).
Scheme 1 Synthetic approach to dendritic polyuracils LnU-OBn (n = 2–4).
Reagents and conditions, i, HBr, AcOH, dioxane, r.t., 12 h; ii, 1, K2CO3,
DMF, r.t., 12 h.
DOI: 10.1039/b000318m
Chem. Commun., 2000, 719–720
This journal is © The Royal Society of Chemistry 2000
719

Fig. 4 Spectroscopic titration of an MeCN solution of a 1+2 mixture of LnU-
OBn (10 mM) (n = 3 [8], 4 [5]) and La(OTf)3 (20 mM) with MeOH at
25 °C monitored at 296.6 nm. Plots of (Aobs 2 Af)/(Ac 2 Af) vs. vol.% of
MeOH.
Fig. 2 Spectroscopic titration of MeCN solutions of LnU-OBn (10 mM) (n
= 3 [8], 4 [5]) with La(OTf)3 at 25 °C monitored at 296.6 nm. Plots of
(Aobs 2 Af)/(Ac 2 Af) vs. [La(OTf)3]0/[LnU-OBn]0. Aobs represents the
observed absorbance, while Af and Ac denote the absorbances of free and
complexed uracil units, respectively. Inset: absorption spectral change.
Na+, K+, Zn2+, Cu+, Cu2+ or Ag+ (triflate salts) having a
preference for lower coordination numbers.
Dendrimer complexes of lanthanide ions have attracted
attention as luminescent materials4 and have also been applied
as MRI contrast agents.5 On the other hand, a nucleobase
complex of a transition metal such as platinum has been studied
for biomedical applications.14 The new metal-ligating nucleo-
base dendrimer consisting of uracil units may therefore have
good potential for a variety of applications in materials science
and medicinal chemistry.
Notes and references
1 Reviews on dendrimers, see: D. A. Tomalia, Adv. Mater., 1994, 6, 529;
J. M. J. Fréchet, Science, 1994, 263, 1710; F. Zeng and S. C.
Zimmerman, Chem. Rev., 1997, 97, 1681; M. Fischer and F. Vögtle,
Angew. Chem., Int. Ed., 1999, 38, 884.
2 M. W. P. L. Baars, P. E. Froehling and E. W. Meijer, Chem. Commun.,
1997, 1959; A. I. Cooper, J. D. Londono, G. Wignall, J. B. McClain,
E. T. Samulski, J. S. Lin, A. Dobrynin, M. Rubinstein, A. L. C. Burke,
J. M. J. Fréchet and J. M. DeSimone, Nature, 1997, 389, 368.
3 L. Balogh and D. A. Tomalia, J. Am. Chem. Soc., 1998, 120, 7355; M.
Zhao and R. M. Crooks, Angew. Chem., Int. Ed., 1999, 38, 364.
4 M. Kawa and J. M. J. Fréchet, Chem. Mater., 1998, 10, 286.
5 E. Tóth, D. Pubanz, S. Vauthey, L. Helm and A. E. Merbach, Chem.
Eur. J., 1996, 2, 1607.
6 Examples of complexation of rare-earth metal ions, see: H. Maumela,
R. D. Hancock, L. Carlton, J. H. Reibenspies and K. P. Wainwright,
J. Am. Chem. Soc., 1995, 117, 6698; Y. Liu, B.-H. Han, Y.-M. Li, R.-T.
Chen, M. Ouchi and Y. Inoue, J. Phys. Chem., 1996, 100, 17361; J. M.
Harrowfield, M. Mocerino, B. J. Peachey, B. W. Skelton and A. H.
White, J. Chem. Soc., Dalton Trans., 1996, 1687 and references therein;
F. Renaud, C. Piguet, G. Bernardinelli, J.-C. G. Bünzli and G.
Hopfgartner, J. Am. Chem. Soc., 1999, 121, 9326.
Fig. 3 IR spectra of (a) L3U-OBn (2.5 mM) and (b) a 1+2 mixture of L3U-
OBn and La(OTf)3 (2.5, 5.0 mM) in MeCN at 20 °C.
appeared at the expense of the non-coordinated C(4NO band
[Fig. 3(b)]. Considering also a small shift due to the C(2)NO
frequency (1708 to 1714 cm21), the C(4)NO functionality is
likely involved predominantly in the complexation with La3+.12
As estimated from the decrease in integral area of the free
C(4)NO band at 1665 cm21 13 an La3+ ion accommodates four
,
out of seven C(4)NO groups in L3U-OBn for complexation. On
the other hand, in the complexation with higher-generation
L4U-OBn having fifteen C(4)NO groups, seven C(4)NO groups
were estimated to coordinate to a La3+ ion.
7 L. Bérillon, R. Wagner and P. Knochel, J. Org. Chem., 1998, 63,
9117.
From the above results, it is expected that La3+ ion is trapped
by L4U-OBn more strongly than lower-generation L3U-OBn.
In fact, the L4U-OBn–La3+ complex was highly robust towards
methanolysis: when an MeCN solution of a mixture of L3U-
OBn (10 mM) and La(OTf)3 (20 mM) was titrated with MeOH
(Fig. 4), the absorption spectral change at 296.6 nm showed a
complete dissociation of La3+ from L3U-OBn at a MeOH
content of 40%. On the other hand, the L4U-OBn–La3+
complex showed a spectral profile of only 30% dissociation
under the same conditions (Fig. 4).
8 Full synthetic and spectroscopic details will be reported elsewhere.
9 R. Anwander and W. A. Herrmann, Top. Curr. Chem., 1996, 179, 1.
10 Owing to the strong complexation, the titration profiles did not allow
determination of the association constants: K. A. Connors, Binding
Constants: the measurement of molecular complex stability, Wiley,
New York, 1987.
11 Y. Kyogoku, R. C. Lord and A. Rich, J. Am. Chem. Soc., 1967, 89,
496.
12 This is possibly due to a high coordination ability of the C(4)NO oxygen
due to the presence of a conjugated vinyl group (M. Tominaga, K.
Konishi and T. Aida, J. Am. Chem. Soc., 1999, 121, 7704).
13 The spectra at 1500–1800 cm21 were analysed with curve-resolving
software by combination of Lorenz and Gaussian curves. A vibrational
band centered at 1647 cm21 is likely to include CNC stretching
frequencies of the uracil and benzyl moieties.
14 S. J. Lippard and J. M. Berg, Principles of Bioinorganic Chemistry,
University Science Books, Mill Valley, CA, 1994; B. Lippert,,
Biometals, 1992, 5, 195; H. Sigel, Chem. Soc. Rev., 1993, 22, 255.
The high activity of LnU-OBn for the complexation with
La3+ is considered to take great advantage of the multidentate
coordination characteristics of the dendritic polyuracil archi-
tecture, since non-dendritic L1U-OBn did not show any
substantial spectral changes upon mixing with La(OTf)3.
Spectral changes were also small when LnU-OBn (n = 3, 4)
were mixed (1+1 mol ratio; in MeCN) with metal ions such as
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Chem. Commun., 2000, 719–720