Solvent Dependent Leaving Group Fluorine Kinetic Isotope Effect in a Nucleophilic Aromatic Substitution Reaction

1996 ◽  
Vol 118 (1) ◽  
pp. 20-23 ◽  
Author(s):  
Jonas Persson ◽  
Svante Axelsson ◽  
Olle Matsson
Keyword(s):  
Isotope Effect ◽  
Substitution Reaction ◽  
Kinetic Isotope Effect ◽  
Nucleophilic Aromatic Substitution ◽  
Aromatic Substitution ◽  
Kinetic Isotope ◽  
Leaving Group

Solvent effects on the structure of SN2 transition states

1978 ◽  
Vol 56 (20) ◽  
pp. 2691-2699 ◽  
Author(s):  
Kenneth Charles Westaway
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Solvent Effects ◽  
Kinetic Isotope Effect ◽  
Transition States ◽  
State Structure ◽  
Transition State Structure ◽  
Kinetic Isotope ◽  
Wide Range ◽  
Leaving Group

Two research groups have used heavy atom leaving group kinetic isotope effects to determine how the structure of an SN2 transition state is affected by a change in solvent. Two completely different types of behaviour were observed in these studies. In one case, the leaving group kinetic isotope effect, and thus the transition state structure, changed markedly when the solvent was varied over a reasonably narrow range. In the other study, the leaving group kinetic isotope effect (transition state structure) remained constant over a wide range of solvents. A model describing the interaction between solvent molecules and SN2 transition states is developed and a SolvationruleforSN2reactions which rationalizes the different experimental results is explained and justified. Finally, predictions based on the solvation rule are shown to be in agreement with the results of theoretical calculations of solvent effects on SN2 transition states and secondary α deuterium kinetic isotope effect measurements.

scholarly journals A kinetic-isotope-effect study of catalysis by Vibrio cholerae neuraminidase

1993 ◽  
Vol 294 (3) ◽  
pp. 653-656 ◽  
Author(s):  
X Guo ◽  
M L Sinnott
Keyword(s):  
Vibrio Cholerae ◽  
Isotope Effect ◽  
Kinetic Isotope Effect ◽  
Isotope Effects ◽  
Effect Study ◽  
K Value ◽  
Rate Determining Step ◽  
Kinetic Isotope ◽  
Leaving Group ◽  
Optimum Ph

Michaelis-Menten parameters for hydrolysis of seven aryl N-acetyl alpha-D-neuraminides by Vibrio cholerae neuraminidase at pH 5.0 correlate well with the leaving-group pKa (delta pK 3.0; beta 1g (V/K) = -0.73, r = -0.93; beta 1g (V) = -0.25; r = -0.95). The beta-deuterium kinetic-isotope effect, beta D2(V), for the p-nitrophenyl glycoside is the same at the optimum pH of 5.0 (1.059 +/- 0.010) as at pH 8.0 (1.053 +/- 0.010), suggesting that isotope effects are fully expressed with this substrate at the optimum pH. For this substrate at pH 5.0, leaving group 18O effects are 18(V) = 1.040 +/- 0.016 and 18(V/K) = 1.046 +/- 0.015, and individual secondary deuterium effects are beta proRD(V) = 1.037 +/- 0.014, beta proSD(V) = 1.018 +/- 0.015, beta proRD(V/K) = 1.030 +/- 0.017, beta proSD(V/K) = 1.030 +/- 0.017. All isotope effects, and the beta 1g(V/K) value are in accord with the first chemical step being both the first irreversible and the rate-determining step in enzyme turnover, with a transition state in which there is little proton donation to the leaving group, the C-O bond is largely cleaved, there is significant nucleophilic participation, and the sugar ring is in a conformation derived from the ground-state 2C5 chair. The apparent conflict between the beta 1g (V) value of -0.25 with all the kinetic-isotope-effect data can be resolved by the postulation of an interaction between the pi system of the aglycone ring and an anionic or nucleophilic group on the enzyme.

The base-catalysed anomerization of dinitrophenyl glycosides: evidence for a novel reaction mechanism

1990 ◽  
Vol 68 (10) ◽  
pp. 1859-1866 ◽  
Author(s):  
Leise A. Berven ◽  
David Dolphin ◽  
Stephen G. Withers
Keyword(s):  
Reaction Mechanism ◽  
Reaction Rate ◽  
Kinetic Isotope Effect ◽  
Substituent Effects ◽  
Proton Exchange ◽  
Nucleophilic Aromatic Substitution ◽  
Aromatic Substitution ◽  
Proton Abstraction ◽  
Sugar Moiety ◽  
Kinetic Isotope

The mechanism of base-catalysed anomerization of per-O-acetylated 2,4-dinitrophenyl-β-D-glucopyranoside in dimethylsulfoxide has been investigated using a variety of techniques. A mechanism involving proton abstraction at C-1 was eliminated by the absence of proton exchange at that center and the measurement of a secondary deuterium kinetic isotope effect for the 1-deuterio substrate. A mechanism involving phenolate departure and recombination is rendered unlikely on the basis of remote substituent effects on the reaction rate and by the absence of any exchange of the phenyl moiety with added phenolate. A mechanism involving nucleophilic aromatic substitution initiated by an attack of the dimethylsulfinyl anion to generate a glucosyl oxyanion intermediate that anomerizes and recombines with the reactive aryl intermediate is consistent with the observations. This mechanism is further supported by the observation of a purple Meisenheimer complex intermediate and by the observed exchange between the substrate containing a labelled sugar moiety and added unlabelled 2,3,4,6-tetra-O-acetyl-β-D-glucopyranose. Keywords: glycoside, anomerization, reaction mechanism.

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