ChemInform Abstract: Two-Metal Ion Catalysis in Enzymatic Acyl- and Phosphoryl-Transfer Reactions

ChemInform ◽  
2010 ◽  
Vol 28 (1) ◽  
pp. no-no
Author(s):  
N. STRAETER ◽  
W. N. LIPSCOMB ◽  
T. KLABUNDE ◽  
B. KREBS
Keyword(s):  
Metal Ion ◽  
Transfer Reactions ◽  
Phosphoryl Transfer ◽  
Metal Ion Catalysis

Two-Metal Ion Catalysis in Enzymatic Acyl- and Phosphoryl-Transfer Reactions

1996 ◽  
Vol 35 (18) ◽  
pp. 2024-2055 ◽  
Author(s):  
Norbert Sträter ◽  
William N. Lipscomb ◽  
Thomas Klabunde ◽  
Bernt Krebs
Keyword(s):  
Metal Ion ◽  
Transfer Reactions ◽  
Phosphoryl Transfer ◽  
Metal Ion Catalysis

Alkali metal ion catalysis in nucleophilic displacement by ethoxide ion on p-nitrophenyl phenylphosphonate: Evidence for multiple metal ion catalysis

2003 ◽  
Vol 81 (1) ◽  
pp. 53-63 ◽  
Author(s):  
Erwin Buncel ◽  
Ruby Nagelkerke ◽  
Gregory RJ Thatcher
Keyword(s):  
Alkali Metal ◽  
Transition State ◽  
Metal Ions ◽  
Metal Ion ◽  
Alkali Metal Ions ◽  
Phosphoryl Transfer ◽  
Alkali Metal Ion ◽  
Nucleophilic Displacement ◽  
Displacement Reactions ◽  
Metal Ion Catalysis

In continuation of our studies of alkali metal ion catalysis and inhibition at carbon, phosphorus, and sulfur centers, the role of alkali metal ions in nucleophilic displacement reactions of p-nitrophenyl phenylphosphonate (PNPP) has been examined. All alkali metal ions studied acted as catalysts. Alkali metal ions added as inert salts increased the rate while decreased rate resulted on M+ complexation with 18-crown-6 ether. Kinetic analysis indicated the interaction of possibly three potassium ions, four sodium ions, and five lithium ions in the transition state of the reactions of ethoxide with PNPP. Pre-association of the anionic substrate with two metals ions in the ground state gave the best fit to the experimental data of the sodium system. Thus, the study gives evidence of the role of several metal ions in nucleophilic displacement reactions of ethoxide with anionic PNPP, both in the ground state and in the transition state. Molecular modeling of the anionic transition state implies that the size of the monovalent cation and the steric requirement of the pentacoordinate transition state are the primary limitations on the number of cations that can be brought to bear to stabilize the transition state and catalyze nucleophilic substitution at phosphorus. The bearing of the present work on metal ion catalysis in enzyme systems is discussed, in particular enzymes that catalyze phosphoryl transfer, which often employ multiple metal ions. Our results, both kinetic and modeling, reveal the importance of electrostatic stabilization of the transition state for phosphoryl transfer that may be effected by multiple cations, either monovalent metal ions or amino acid residues. The more such cations can be brought into contact with the anionic transition state, the greater the catalysis observed.Key words: alkali metal ion catalysis, nucleophilic displacement at phosphorus, multiple metal ion catalysis, phosphoryl transfer.

2004 Bader Award LectureMetal-ion-catalyzed acyl and phosphoryl transfer reactions to alcohols: La3+-promoted alcoholysis of activated amides, carboxylate esters, and neutral organophosphorus esters

2004 ◽  
Vol 82 (12) ◽  
pp. 1791-1805 ◽  
Author(s):  
R Stan Brown ◽  
Alexei A Neverov ◽  
Josephine SW Tsang ◽  
Graham TT Gibson ◽  
Pedro J Montoya-Pelaez
Keyword(s):  
Rate Constant ◽  
Metal Ion ◽  
Active Form ◽  
Transfer Reactions ◽  
Nucleophilic Attack ◽  
Phosphoryl Transfer ◽  
Solution Ph ◽  
Activated Esters ◽  
Neutral Ph ◽  
Kinetics Of

Unlike metal-ion-catalyzed hydrolysis processes, metal-ion-catalyzed methanolysis processes have received scant attention in the literature particularly from the standpoint of mechanistic studies. La3+, introduced into methanol solution as its triflate or perchlorate salt, is particularly effective in promoting methanolysis reactions of unactivated and activated esters, phosphate triesters, and activated amides such as acetyl imidazoles and lactams. Studies of the kinetics of methanolysis of these substrates as a function of solution pH and [La3+] indicate that the solution comprises lanthanum dimers with one to five associated methoxides (La23+(–OCH3)1–5), the most catalytically active form being La23+(–OCH3)2, which is produced at near neutral pH in methanol (8.4). Mechanisms for all the acyl and phosphoryl transfer reactions are proposed where the metal ion serves a dual role of acting as a Lewis acid to activate the C=O or P=O system to nucleophilic attack by a metal-coordinated methoxide nucleophile. In cases where direct comparisons can be made, the La23+ catalyst system is more active for the methanolysis of nonactivated substrates than for activated substrates. Another general characteristic of this system is that the catalytic rate constant for the metal complex exceeds the second-order rate constant for free methoxide, in some cases by as much as 4600-fold. Overall the catalytic effects exhibited by the La23+ system is spectacular for such substrates as paraoxon, where as little as 2 mmol L–1 La(OTf)3 in the presence of equimolar NaOCH3 accelerates the methanolysis by 109-fold relative to the background reaction at neutral pH and ambient temperature.Key words: kinetics of methanolysis, metal ion catalysis, lanthanides, methanolysis of carboxylate esters and phosphate esters.

Bio-inspired approaches to accelerating metal ion-promoted reactions: enzyme-like rates for metal ion mediated phosphoryl and acyl transfer processes

2015 ◽  
Vol 87 (6) ◽  
pp. 601-614 ◽  
Author(s):  
Robert Stan Brown
Keyword(s):  
Metal Ion ◽  
Catalytic Efficiency ◽  
Acyl Transfer ◽  
Transfer Reactions ◽  
Medium Effect ◽  
Phosphoryl Transfer ◽  
Leaving Group ◽  
Bonding Properties ◽  
Catalyzed Reactions ◽  
Phosphate Diesters

Abstract Intense efforts by many research groups for more than 50 years have been directed at biomimetic approaches to understand how enzymes achieve their remarkable rate accelerations. Nevertheless, it was noted in 2003 that, despite numerous efforts to design models for catalyzing the cleavage of such species as phosphate diesters, “none of the several models so far described approaches the enormous catalytic efficiency of natural enzymes”. The same could be said for biomimetics of other enzymes promoting acyl or phosphoryl transfer reactions, particularly those mediated by metal ions such as Zn(II). Clearly other important factors were being overlooked or awaiting discovery. In this manuscript we describe two important effects that we have implemented to accelerate metal ion catayzed phosphoryl and acyl transfer reactions. The first of these relates to a medium effect where the polarity of the solution, as measured by dielectric constant, is reduced from that of water (ε = 78) to values of 31.5 and 24.3 when the solvent is changed to methanol or ethanol. Among organic solvents these light alcohols are closest to water in terms of structure and properties as well as retaining important H-bonding properties. The second important effect involves a known but difficult to demonstrate mode of catalysis where the leaving group (LG) in a solvolysis reaction is accelerated as it becomes progressively poorer. In the cases described herein, the LG’s propensity to depart from a substrate during the course of reaction is accelerated by coordination to a metal ion in a process known as leaving group assistance, or LGA. These two effects can each impart accelerations of 109–1017 for certain metal ion catalyzed reactions relative to the corresponding solvent, or base induced reactions.

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