Angewandte
Chemie
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Figure 5. The hydrolysis of UpU (0.06 mm) catalyzed by [Zn2(1)]
(1 mm) in HEPES buffer (50 mm, pH 7.3) at 258C. The solid line is the
least-squares fit to a first-order decay.
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cleavage of unactivated substrates relative to double Lewis
acid activation by the ZnII ions alone.[15] As shown by the
crystal structure in Figure 1, the phosphoryl moiety can bridge
the two ZnII ion centers to benefit from double Lewis acid
activation, thus simultaneously placing the phosphoryl
oxygen atoms in hydrogen-bonding distance of the amino
groups. This enhances binding to the substrate, which is
substantially tighter than in comparable complexes, and to the
transition state, which leads to the high reactivity.
In summary, we have combined two strategies to achieve
tight phosphate binding and high catalytic activity for
phosphodiester transesterification with a synthetic ZnII com-
plex. Our kinetic studies show that this dinuclear complex
shows remarkable rate enhancement both for the activated
substrate HPNPP and UpU. This efficiency comes from the
cooperation of double Lewis acid activation through two ZnII
ions and the hydrogen-bonding environment provided by the
ligand. We are currently exploring whether these approaches
can be used even more effectively to extend the limits of
activity of small molecules to rival biological catalysts and to
develop phosphate receptors with new practical applica-
tions.[16]
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[9] ESI mass-spectrometric analysis of an aqueous solution of the
ligand 1 (1 mm; HCl salt), PNPP, and two equivalents of
Zn(NO3)2 revealed peaks that correspond to the expected
mass and isotope for [Zn2(1)]·PNPP, thus suggesting that the
complex persists in water as well as the solid phase.
[10] E. Kinoshita, M. Takahashi, H. Takada, M. Shiro, T. Koike,
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[11] Binding of monoanionic phosphate diesters to [Zn2(1)] in water
is even stronger than to CoIII complexes.[6a]
[12] This rate constant is slightly less than that measured by Richards
and co-workers (0.25mꢁ1 sꢁ1) for the catalysis of the transesteri-
fication of HPNPP by a triazacyclononane-based dinuclear Zn
complex through double Lewis acid activation.[4c] [Zn2(1)] is
about 200-fold more effective under similar reaction conditions.
[13] K. Worm, F. Chu, K. Matsumoto, M. D. Best, V. Lynch, E. V.
Anslyn, Chem. Eur. J. 2003, 9, 741.
Received: June 23, 2006
Published online: September 29, 2006
Keywords: dinuclear complexes · enzyme models ·
.
hydrogen bonds · phosphate ester cleavage · receptors
[14] A. OꢀDonoghue, S. Y. Pyun, M.-Y. Yang, J. R. Morrow, J. P.
Richard, J. Am. Chem. Soc. 2006, 128, 1615.
[15] Cleavage of ApA by the ZnII complex of the pyridyl-based
ligand with no 2-amino substituents has been reported at 508C
and pH 7.0 with a concentration of 2.5 mm for the complex (M.
Yashiro, A. Ishikubo, M. Komiyama, Chem. Commun. 1995,
1793), thus giving kobs ꢂ 2 10ꢁ5 sꢁ1. Allowing for the different
conditions, a similar value is estimated to that reported in
reference [14] for our reaction conditions.
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[16] Experimental details can be found in the Supporting Informa-
tion.
[2] S. Aoki, E. Kimura, Rev. Mol. Biotechnol. 2002, 90, 129, and
references therein.
Angew. Chem. Int. Ed. 2006, 45, 7056 –7059
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