scholarly journals Enzyme-Specific Activation versus Leaving Group Ability

ChemBioChem ◽  
2012 ◽  
Vol 13 (12) ◽  
pp. 1785-1790 ◽  
Author(s):  
Roseri J. A. C. de Beer ◽  
Berry Bögels ◽  
Gijs Schaftenaar ◽  
Barbara Zarzycka ◽  
Peter J. L. M. Quaedflieg ◽  
...  
Keyword(s):  
Leaving Group ◽  
Leaving Group Ability

Leaving group ability in base-promoted alkene-forming 1,2-eliminations

1975 ◽  
pp. 940 ◽  
Author(s):  
Donald R. Marshall ◽  
Patsy J. Thomas ◽  
Charles J. M. Stirling
Keyword(s):  
Leaving Group ◽  
Leaving Group Ability

scholarly journals Leaving Group Ability in Nucleophilic Aromatic Amination by Sodium Hydride–Lithium Iodide Composite

Synthesis ◽  
2019 ◽  
Vol 52 (03) ◽  
pp. 393-398
Author(s):  
Jia Hao Pang ◽  
Derek Yiren Ong ◽  
Kohei Watanabe ◽  
Ryo Takita ◽  
Shunsuke Chiba
Keyword(s):  
Nucleophilic Substitution ◽  
Methoxy Group ◽  
Sodium Hydride ◽  
Lithium Iodide ◽  
Substitution Reactions ◽  
Computational Approaches ◽  
Nucleophilic Substitution Reactions ◽  
Leaving Group ◽  
Leaving Group Ability

The methoxy group is generally considered as a poor leaving group for nucleophilic substitution reactions. This work verified the superior ability of the methoxy group in nucleophilic amination of arenes mediated by the sodium hydride and lithium iodide through experimental and computational approaches.

scholarly journals Nucleophilic substitution at di- and triphosphates: leaving group ability of phosphate versus diphosphate

2019 ◽  
Vol 1 (2) ◽  
pp. 024001 ◽  
Author(s):  
Bas van Beek ◽  
Marc A van Bochove ◽  
Trevor A Hamlin ◽  
F Matthias Bickelhaupt
Keyword(s):  
Nucleophilic Substitution ◽  
Leaving Group ◽  
Leaving Group Ability

scholarly journals Transition State Interactions in a Promiscuous Enzyme: Sulfate and Phosphate Monoester Hydrolysis byPseudomonas aeruginosaArylsulfatase

2018 ◽  
Author(s):  
Bert van Loo ◽  
Ryan Berry ◽  
Usa Boonyuen ◽  
Mark F. Mohamed ◽  
Marko Golicnik ◽  
...  
Keyword(s):  
Active Site ◽  
Isotope Effects ◽  
Charge Compensation ◽  
Linear Free Energy ◽  
Uncatalyzed Reaction ◽  
Leaving Group ◽  
Energy Relationships ◽  
Increased Sensitivity ◽  
Leaving Group Ability ◽  
Active Site Mutants

ABSTRACTPseudomonas aeruginosaarylsulfatase (PAS) hydrolyses sulfate and, promiscuously, phosphate monoesters. Enzyme-catalyzed sulfate transfer is crucial to a wide variety of biological processes, but detailed studies of the mechanistic contributions to its catalysis are lacking. We present an investigation based on linear free energy relationships (LFERs) and kinetic isotope effects (KIEs) of PAS and active site mutants that suggest a key role for leaving group (LG) stabilization. In LFERs wild type PAS has a much less negative Br0nsted coefficient (βleaving groupobs-Enz= −0.33) than the uncatalyzed reaction (βleavingroupobs= −1.81). This situation is diminished when cationic active site groups are exchanged for alanine. The considerable degree of bond breaking during the TS is evidenced by an18ObridgeKIE of 1.0088. LFER and KIE data for several active site mutants point to leaving group stabilization by active-site lysine K375, in cooperation with histidine H211.15N KIEs combined with an increased sensitivity to leaving group ability of the sulfatase activity in neat D2O (Δβleaving groupH-D= +0.06) suggest that the mechanism for S-Obridgebond fission shifts, with decreasing leaving group ability, from charge compensation via Lewis acid interactions towards direct proton donation.18OnonbridgeKIEs indicate that the TS for PAS-catalyzed sulfate monoester hydrolysis has a significantly more associative character compared to the uncatalyzed reaction, while PAS-catalyzed phosphate monoester hydrolysis does not show this shift. This difference in enzyme-catalyzed TSs appears to be the major factor favoring specificity toward sulfate over phosphate in this promiscuous hydrolase, since other features are either too similar (uncatalyzed TS) or inherently favor phosphate (charge).

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