Double Lewis Acid Activation in Phosphate Diester Cleavage

Wall, Mark; Hynes, Rosemary C.; Chin, Jik

doi:10.1002/anie.199316331

Cited by 139 publications

(61 citation statements)

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“…A mechanism that is consistent with the pH dependence as well as the rate-ratio for complex 1 promoted transesterification of HPNP, as shown in Scheme 2. Such double Lewis-acid activation mechanism had been proposed for dinuclear metal complexes promoted cleavage of phosphate diester [45,46].…”

Section: Ph and R-dependent Kinetic Studies On The Hydrolysis Of Hpnpmentioning

confidence: 91%

A Novel Dinucleating Ligand-Containing Hexabenzimidazoles and Its Dinuclear Zinc Complex Bridged by a Carboxylate Group for the Hydrolysis of 2-Hydroxypropyl-p-nitrophenyl phosphate

Ibrahim

2009

J Inorg Organomet Polym

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Section: Ph and R-dependent Kinetic Studies On The Hydrolysis Of Hpnpmentioning

confidence: 91%

A Novel Dinucleating Ligand-Containing Hexabenzimidazoles and Its Dinuclear Zinc Complex Bridged by a Carboxylate Group for the Hydrolysis of 2-Hydroxypropyl-p-nitrophenyl phosphate

Ibrahim

2009

J Inorg Organomet Polym

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“…[12][13][14][15] Such bimetallic cooperativity has been observed in the hydrolysis of phosphate esters by dinuclear copper(II) and zinc(II) complexes. [12][13][14][15][29][30][31][32] For example, in the hydrolysis of phosphate monoester, a 50-fold enhancement in the rate of reaction was observed when two bis(benzimidazolyl)cop-per(II) units linked by a bridging 2-phenoxy-1,3-xylyl group were used compared to the corresponding monomer. [29] A dinuclear copper(II) complex with two 1,4,7-triazacyclononane (tacn) units and naphthalenyl spacer groups accelerates the cleavage of the RNA model ApA by a factor of about 10 5 , which is about 520 times more reactive per metal center (pH = 6, 25°C) than its monomeric analog.…”

Section: Introductionmentioning

confidence: 99%

DNA Cleavage by Structurally Characterized Dinuclear Copper(II) Complexes Based on Triazine

Massoud

Louka

et al. 2011

Eur J Inorg Chem

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The reaction of 2‐chloro‐4,6‐bis(di‐2‐picolylamino)‐1,3,5‐triazine (bdpaTCl) with copper(II) perchlorate and copper(II) chloride afforded two dinuclear complexes [Cu2(μ‐bdpaTCl)(μ‐OH)2(H2O)0.5(ClO4)0.5](ClO4)1.5·(H2O)1.5 (1) and [Cu2(μ‐bdpaTCl)Cl4]·2CH3OH (2), respectively. These complexes were characterized by IR, UV/Vis, and EPR spectroscopy, single‐crystal X‐ray crystallography, and temperature dependence magnetic susceptibility measurements (2–300 K) as well as by electrochemical and molar conductivity measurements. In 1, each of the three N‐donor atoms of the binucleating bdpaTCl ligand coordinate to CuII ions, which are further bridged by two OH– anions in a distorted five‐coordinate geometry. In addition, each CuII ion forms a Cu–O semicoordinate bond with an aqua ligand or perchlorato anion. The Cu···Cu distance across the hydroxido bridges is 2.9698(11) Å. In 2, the bdpaTCl ligand acts as bis‐tridentate ligand connecting the two CuII ions, and the five‐coordinate geometry around each copper center is achieved by two terminal chloro ligands. Magnetic measurements revealed strong antiferromagnetic coupling in 1 (J = –311.2 cm–1) and very weak coupling in 2 (J = –2.4 cm–1). DNA cleavage by these two complexes has been investigated (pH = 7.0, 37 °C). Although the bridged dihydroxido complex 1 did not show any detectable cleavage for DNA, significant cleavage was observed with the tetrachloro complex 2. Under pseudo‐Michaelis–Menten kinetic conditions, the kinetic parameters kcat = 2.53 × 10–5 s–1 and KM = 1.44 × 10–4 M were determined for 2. The kcat value corresponds to a 2.5 × 106 fold rate enhancement over noncatalyzed DNA. Electrophoretic experiments conducted in the presence and absence of oxidative scavengers DMSO, KI, and NaN3, and radical promoter H2O2 provide evidence for the oxidative cleavage of DNA by hydroxy radicals and hydrogen peroxide species.

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“…Therefore, present kinetic evidence demands that we invoke the double-metal-ion mechanism of catalysis for reactions catalyzed by hammerhead ribozymes (17), regardless of the presence or absence of the pentacoordinate intermediates. Such double-metal-ion catalysis has been proven to be an efficient mechanism for the cleavage of phosphodiester bonds in nonenzymatic reactions (50)(51)(52)(53)(54)(55).…”

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confidence: 99%

Explanation by the double-metal-ion mechanism of catalysis for the differential metal ion effects on the cleavage rates of 5′-oxy and 5′-thio substrates by a hammerhead ribozyme

Zhou

Zhang

Taira

1997

Proc. Natl. Acad. Sci. U.S.A.

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In a previous examination using natural all-RNA substrates that contained either a 5-oxy or 5-thio leaving group at the cleavage site, we demonstrated that (i) the attack by the 2-oxygen at C17 on the phosphorus atom is the rate-limiting step only for the substrate that contains a 5-thio group (R11S) and (ii) the departure of the 5 leaving group is the rate-limiting step for the natural all-RNA substrate (R11O) in both nonenzymatic and hammerhead ribozyme-catalyzed reactions; the energy diagrams for these reactions were provided in our previous publication. In this report we found that the rate of cleavage of R11O by a hammerhead ribozyme was enhanced 14-fold when Mg 2؉ ions were replaced by Mn 2؉ ions, whereas the rate of cleavage of R11S was enhanced only 2.2-fold when Mg 2؉ ions were replaced by Mn 2؉ ions. This result appears to be exactly the opposite of that predicted from the direct coordination of the metal ion with the leaving 5-oxygen, because a switch in metal ion specificity was not observed with the 5-thio substrate. However, our quantitative analyses based on the previously provided energy diagram indicate that this result is in accord with the double-metal-ion mechanism of catalysis.Among various catalytic RNAs, the hammerhead-type ribozyme is the smallest and best understood as far as the relationship between structure and function is concerned. Naturally occurring hammerhead ribozymes can be found in some RNA viruses, and they act ''in cis'' during viral replication by the rolling circle mechanism (1-3). The hammerhead ribozyme has been engineered in such a way that it can act ''in trans'' against other RNA molecules (4, 5). The trans-acting hammerhead ribozyme developed by Haseloff and Gerlach (5) consists of an antisense section (stems I and III) and a catalytic domain with a flanking stem II and loop section (Fig. 1a). Because of the small size of hammerhead ribozymes, they are well suited for mechanistic studies, being good representatives of catalytic RNAs. Recently, hammerhead ribozymes were crystallized and their structures were analyzed in detail by two independent groups (6-9). The global three-dimensional structures of the two crystallized ribozymes were nearly identical: one domain of the conserved core, which consists of the sequence C 3 U and is located next to stem I, makes a sharp turn identical to the uridine turn in tRNAs (10). As a result, stem II and stem III are aligned almost colinearly through pseudocontinuous, long A-type helices.It is now well established that ribozymes are metalloenzymes (2,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Although x-ray analysis of a hammerhead ribozyme identified one potential catalytic metal ion (7-9), the exact number of metal ions required for catalysis remains obscure, because the newly captured conformational intermediate appears to demand further conformational change for the following in-line attack (9). Direct evidence that a Mg 2ϩ ion acts as a Lewis acid by coordinating directly to the leaving ...

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Double Lewis Acid Activation in Phosphate Diester Cleavage

Cited by 139 publications

References 29 publications

A Novel Dinucleating Ligand-Containing Hexabenzimidazoles and Its Dinuclear Zinc Complex Bridged by a Carboxylate Group for the Hydrolysis of 2-Hydroxypropyl-p-nitrophenyl phosphate

A Novel Dinucleating Ligand-Containing Hexabenzimidazoles and Its Dinuclear Zinc Complex Bridged by a Carboxylate Group for the Hydrolysis of 2-Hydroxypropyl-p-nitrophenyl phosphate

DNA Cleavage by Structurally Characterized Dinuclear Copper(II) Complexes Based on Triazine

Explanation by the double-metal-ion mechanism of catalysis for the differential metal ion effects on the cleavage rates of 5′-oxy and 5′-thio substrates by a hammerhead ribozyme

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