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Dinuclear and Trinuclear Zn(II) Calix[4]arene Complexes as Models for Hydrolytic Metallo-Enzymes. Synthesis and Catalytic Activity in Phosphate Diester Transesterification
journal contribution
posted on 1999-05-07, 00:00 authored by Peter Molenveld, Wendy M. G. Stikvoort, Huub Kooijman, Anthony L. Spek, Johan F. J. Engbersen, David N. ReinhoudtCalix[4]arenes modified with two or three Zn(II)-2,6-bis(aminomethyl)pyridyl groups, 3-[Zn]2 and
5-[Zn]3, respectively, were investigated as models for dinuclear and trinuclear metallo-enzymes
that catalyze the cleavage of phosphate diesters. Under neutral conditions, 0.48 mM of 3-[Zn]2
causes a rate acceleration of 23 000 in the transesterification of the RNA model substrate
2-hydroxyproyl-p-nitrophenyl phosphate (HPNP, 0.19 mM). Comparison with the activities of a
mononuclear complex 2-[Zn] and a reference complex lacking the calix[4]arene backbone 1-[Zn]
shows that the catalysis is due to cooperative action of the Zn(II) centers and indicates that
hydrophobic effects contribute to the catalysis. Saturation kinetics and pH variation studies
demonstrate that the high catalytic activity of the flexible complex 3-[Zn]2 originates from a very
high substrate binding affinity, affording a Michaelis−Menten complex in which the substrate is
converted with a relatively moderate rate. A rigid analogue 4-[Zn]2 exhibits both a lower substrate
binding strength and a lower catalytic rate. This demonstrates the importance of a certain flexibility
between the cooperating catalytic centers. The trinuclear complex 5-[Zn]3 induces a rate acceleration
of 32 000 times, and shows a decreased substrate binding and an increased catalytic rate compared
to its dinuclear analogue 3-[Zn]2. In a possible mechanism two Zn(II) ions activate the phosphoryl
group and another activates the β-hydroxyl group of HPNP.