Dinuclear and trinuclear Zn(II) calix[4]arene complexes as models for hydrolytic metallo-enzymes. Synthesis and catalytic activity in phosphate diester transesterification

P. Molenveld, Wendy M.G. Stikvoort, Huub Kooijman, Anthony L. Spek, Johannes F.J. Engbersen, David Reinhoudt

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Abstract

Calix[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 B-hydroxyl group of HPNP.
Original languageUndefined
Pages (from-to)3896-3906
JournalJournal of organic chemistry
Volume64
Issue number64
DOIs
Publication statusPublished - 1999

Keywords

  • METIS-105956
  • IR-11024

Cite this

@article{200fa69cbbb047668d8021fc57efb4ce,
title = "Dinuclear and trinuclear Zn(II) calix[4]arene complexes as models for hydrolytic metallo-enzymes. Synthesis and catalytic activity in phosphate diester transesterification",
abstract = "Calix[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 B-hydroxyl group of HPNP.",
keywords = "METIS-105956, IR-11024",
author = "P. Molenveld and Stikvoort, {Wendy M.G.} and Huub Kooijman and Spek, {Anthony L.} and Engbersen, {Johannes F.J.} and David Reinhoudt",
year = "1999",
doi = "10.1021/jo982201f",
language = "Undefined",
volume = "64",
pages = "3896--3906",
journal = "Journal of organic chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "64",

}

Dinuclear and trinuclear Zn(II) calix[4]arene complexes as models for hydrolytic metallo-enzymes. Synthesis and catalytic activity in phosphate diester transesterification. / Molenveld, P.; Stikvoort, Wendy M.G.; Kooijman, Huub; Spek, Anthony L.; Engbersen, Johannes F.J.; Reinhoudt, David.

In: Journal of organic chemistry, Vol. 64, No. 64, 1999, p. 3896-3906.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Dinuclear and trinuclear Zn(II) calix[4]arene complexes as models for hydrolytic metallo-enzymes. Synthesis and catalytic activity in phosphate diester transesterification

AU - Molenveld, P.

AU - Stikvoort, Wendy M.G.

AU - Kooijman, Huub

AU - Spek, Anthony L.

AU - Engbersen, Johannes F.J.

AU - Reinhoudt, David

PY - 1999

Y1 - 1999

N2 - Calix[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 B-hydroxyl group of HPNP.

AB - Calix[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 B-hydroxyl group of HPNP.

KW - METIS-105956

KW - IR-11024

U2 - 10.1021/jo982201f

DO - 10.1021/jo982201f

M3 - Article

VL - 64

SP - 3896

EP - 3906

JO - Journal of organic chemistry

JF - Journal of organic chemistry

SN - 0022-3263

IS - 64

ER -