On the origin of base concentration effect on stereo- and regioselectivity in alkoxide-promoted E2 reactions: A consequence of substrate solvation by metal ions

1990 ◽  
Vol 55 (3) ◽  
pp. 695-703 ◽  
Author(s):  
Jiří Závada ◽  
Magdalena Pánková ◽  
Antonín Vítek
Keyword(s):  
Transition State ◽  
Metal Ions ◽  
Concentration Effect ◽  
Distribution Data ◽  
Title Problem ◽  
Inert Salt

The title problem has been investigated in the reaction of 2-decyl bromide with t-C4H9OK/t-C4H9OH system employing 18-crown-6 ether and an "inert" salt (t-C4H9OLi) as mechanistic probes. From olefin-distribution data and a subsidiary kinetic evidence it has been inferred that the investigated effect originates from a concentration-dependent substrate solvation by metal ions in the transition state.

The transition state for exchange of protons and metal ions in a carboxylate ion-exchange resin

1977 ◽  
Vol 99 (18) ◽  
pp. 5916-5919 ◽  
Author(s):  
Julio F. Mata-Segreda ◽  
Siegfried Lindenbaum ◽  
Richard L. Schowen
Keyword(s):  
Ion Exchange ◽  
Transition State ◽  
Metal Ions ◽  
Exchange Resin ◽  
Ion Exchange Resin

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.

Catalytic pathways in the ethanolysis of fenitrothion, an organophosphorothioate pesticide. A dichotomy in the behaviour of crown/cryptand cation complexing agents

2001 ◽  
Vol 79 (2) ◽  
pp. 157-173 ◽  
Author(s):  
Vimal K Balakrishnan ◽  
Julian M Dust ◽  
Gary W vanLoon ◽  
Erwin Buncel
Keyword(s):  
Alkali Metal ◽  
Transition State ◽  
Metal Ions ◽  
Metal Ion ◽  
Alkali Metals ◽  
Rate Coefficients ◽  
Nucleophilic Attack ◽  
Complexing Agents ◽  
Product Analysis ◽  
Aliphatic Carbon

The rates of displacement of 3-methyl-4-nitrophenoxide ion from the pesticide, fenitrothion, by alkali metal ethoxides in anhydrous ethanol were followed spectrophotometrically. Through product analysis experiments, which included 31P NMR and GC-MS, as well as spectrophotometric analysis, three reaction pathways were identified: nucleophilic attack at the phosphorus centre, attack at the aliphatic carbon, and a minor SNAr route ([Formula: see text]7%). Furthermore, a consecutive process was found to occur on the product of attack at the phosphorus centre. For purposes of kinetic treatment, the processes at the aliphatic and aromatic carbon were combined (i.e., the minor SNAr pathway was neglected), and the observed reaction rate constants were dissected into rate coefficients for nucleophilic attack at phosphorus and at aliphatic carbon. Attack at phosphorus was found to be catalyzed by the alkali metal ethoxides in the order KOEt > NaOEt > LiOEt. Catalysis arises from alkali metal ethoxide aggregates in the base solutions used (0–1.8 M); treatment of the system as a mixture of free ethoxide, ion-paired metal ethoxide, and metal ethoxide dimers resulted in a good fit with the kinetic data. An unexpected dichotomy in the kinetic behaviour of complexing agents (e.g., DC-18-crown-6, [2.2.2]cryptand) indicated that the dimers are more reactive than free ethoxide anions, which are in turn more reactive than ion-paired metal ethoxide. The observed relative order of reactivity is explained in the context of the Eisenman theory in which the free energy of association of the metal ion with the rate-determining transition state is largely determined by the solvent reorganization parameter. In contrast with displacement at the phosphorus centre, attack at the aliphatic carbon was not found to be catalyzed by alkali metals. In this case, the free ethoxide anion was more reactive than either the ion-paired metal ethoxide or the dimeric aggregate. The differing effects of alkali metals on the two pathways is ascribed largely to the leaving group pKa. For carbon attack, the pKa value estimated for demethyl fenitrothion, 2.15, is sufficiently low that metal ions are not required to stabilize the rate-determining transition state. In contrast, for phosphorus attack, 3-methyl-4-nitrophenoxide, with a pKa of 7.15, requires stabilization by metal ion interactions. Hence, alkali metal ions catalyze attack at phosphorus, but not attack at the carbon centres.Key words: organophosphorothioate, pesticide, fenitrothion, ethanolysis, alkali metal ethoxide, ion-pair reactivity, dimers, catalysis, competitive pathways.

Metal ion catalysis in nucleophilic displacement reactions at carbon, phosphorus, and sulfur centers. I. Catalysis by metal ions in the reaction of p-nitrophenyl diphenylphosphinate with ethoxide

1989 ◽  
Vol 67 (9) ◽  
pp. 1440-1448 ◽  
Author(s):  
Edward J. Dunn ◽  
Erwin Buncel
Keyword(s):  
Crown Ether ◽  
Alkali Metal ◽  
Transition State ◽  
Metal Ions ◽  
Ground State ◽  
Metal Ion ◽  
Complexing Agents ◽  
Transition State Stabilization ◽  
Nucleophilic Displacement ◽  
Metal Ion Catalysis

The effect of macrocyclic crown ether and cryptand complexing agents on the rate of the nucleophilic displacement reaction of p-nitrophenyl diphenylphosphinate by alkali metal ethoxides in ethanol at 25 °C has been studied by spectrophotometric techniques. For the reactions of potassium ethoxide, sodium ethoxide, and lithium ethoxide, the observed rate constant increased in the order KOEt < NaOEt < LiOEt. Crown ether and cryptand cation-complexing agents have a retarding effect on the rate. Increasing the ratio of complexing agent to base results in a decrease in kobs to a minimum value corresponding to the rate of reaction of free ethoxide ion. In complementary experiments, alkali metal ions were added to these reaction systems in the form of unreactive salts, causing an increase in reaction rate. The kinetic data were analysed in terms of ion-pairing treatments, which allowed evaluation of rate coefficients due to free ethoxide ions and metal ion – ethoxide ion pairs. Possible roles of the metal cations are discussed in terms of ground state and transition state stabilization. Evaluation of the equilibrium constants for association of the metal ion with ground state (Ka) and the transition state (K′a) shows that catalysis occurs as a result of enhanced association between the metal ion and the transition state, with (K′a) values increasing in the order K+ < Na+ < Li+. A model is proposed in which transition state stabilization arises largely from chelation of the solvated metal ion to two charged oxygen centers. This appears to be the first reported instance of catalysis by alkali metal cations in nucleophilic displacement at phosphoryl centers. Keywords: nucleophilic displacement at phosphorus, alkali-metal-ion catalysis.

scholarly journals The effect of magnesium ions on triphosphate hydrolysis

2017 ◽  
Vol 89 (6) ◽  
pp. 715-727 ◽  
Author(s):  
Alexandre Barrozo ◽  
David Blaha-Nelson ◽  
Nicholas H. Williams ◽  
Shina C. L. Kamerlin
Keyword(s):  
Transition State ◽  
Metal Ions ◽  
Density Functional ◽  
Reaction Pathway ◽  
Enzymatic Reaction ◽  
Phosphate Ester ◽  
Mechanistic Pathway ◽  
Phosphate Hydrolysis ◽  
The Impact

AbstractThe role of metal ions in catalyzing phosphate ester hydrolysis has been the subject of much debate, both in terms of whether they change the transition state structure or mechanistic pathway. Understanding the impact of metal ions on these biologically critical reactions is central to improving our understanding of the role of metal ions in the numerous enzymes that facilitate them. In the present study, we have performed density functional theory studies of the mechanisms of methyl triphosphate and acetyl phosphate hydrolysis in aqueous solution to explore the competition between solvent- and substrate-assisted pathways, and examined the impact of Mg2+ on the energetics and transition state geometries. In both cases, we observe a clear preference for a more dissociative solvent-assisted transition state, which is not significantly changed by coordination of Mg2+. The effect of Mg2+ on the transition state geometries for the two pathways is minimal. While our calculations cannot rule out a substrate-assisted pathway as a possible solution for biological phosphate hydrolysis, they demonstrate that a significantly higher energy barrier needs to be overcome in the enzymatic reaction for this to be an energetically viable reaction pathway.

scholarly journals Probing the mechanisms for the selectivity and promiscuity of methyl parathion hydrolase

2016 ◽  
Vol 374 (2080) ◽  
pp. 20160150 ◽  
Author(s):  
Miha Purg ◽  
Anna Pabis ◽  
Florian Baier ◽  
Nobuhiko Tokuriki ◽  
Colin Jackson ◽  
...  
Keyword(s):  
Transition State ◽  
Metal Ions ◽  
Metal Ion ◽  
Methyl Parathion ◽  
Model Systems ◽  
Functional Evolution ◽  
Methyl Parathion Hydrolase ◽  
Wide Range ◽  
Metal Metal ◽  
Parathion Hydrolase

Diverse organophosphate hydrolases have convergently evolved the ability to hydrolyse man-made organophosphates. Thus, these enzymes are attractive model systems for studying the factors shaping enzyme functional evolution. Methyl parathion hydrolase (MPH) is an enzyme from the metallo-β-lactamase superfamily, which hydrolyses a wide range of organophosphate, aryl ester and lactone substrates. In addition, MPH demonstrates metal-ion-dependent selectivity patterns. The origins of this remain unclear, but are linked to open questions about the more general role of metal ions in functional evolution and divergence within enzyme superfamilies. Here, we present detailed mechanistic studies of the paraoxonase and arylesterase activities of MPH complexed with five different transition metal ions, and demonstrate that the hydrolysis reactions proceed via similar pathways and transition states. However, while it is possible to discern a clear structural origin for the selectivity between different substrates , the selectivity between different metal ions appears to lie instead in the distinct electrostatic properties of the metal ions themselves, which causes subtle changes in transition state geometries and metal–metal distances at the transition state rather than significant structural changes in the active site. While subtle, these differences can be significant for shaping the metal-ion-dependent activity patterns observed for this enzyme. This article is part of the themed issue ‘Multiscale modelling at the physics–chemistry–biology interface’.

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