The Deuterium Isotope Effect on the NMR Signal of the Low-Barrier Hydrogen Bond in a Transition- State Analog Complex of Chymotrypsin

2000 ◽  
Vol 273 (2) ◽  
pp. 789-792 ◽  
Author(s):  
Constance S. Cassidy ◽  
Jing Lin ◽  
Perry A. Frey
Keyword(s):  
Hydrogen Bond ◽  
Transition State ◽  
Isotope Effect ◽  
Deuterium Isotope Effect ◽  
Transition State Analog

scholarly journals A Low-barrier Hydrogen Bond Between Histidine of Secreted Phospholipase A2 and a Transition State Analog Inhibitor

2003 ◽  
Vol 329 (5) ◽  
pp. 997-1009 ◽  
Author(s):  
Ming Jye Poi ◽  
John W. Tomaszewski ◽  
Chunhua Yuan ◽  
Christopher A. Dunlap ◽  
Niels H. Andersen ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Transition State ◽  
Phospholipase A2 ◽  
Transition State Analog ◽  
Secreted Phospholipase A2

Unequal primary kinetic isotope effects in the base-catalysed H–D exchange of diastereotopic protons

1980 ◽  
Vol 58 (1) ◽  
pp. 72-78 ◽  
Author(s):  
Robert R. Fraser ◽  
Philippe J. Champagne
Keyword(s):  
Transition State ◽  
Exchange Reaction ◽  
Isotope Effect ◽  
Isotope Effects ◽  
Kinetic Isotope Effects ◽  
Deuterium Isotope Effect ◽  
Kinetic Isotope

Primary kinetic isotope effects have been measured for the base-catalyzed exchange reaction of 4′,1″-dimethyl-1,2,3,4-dibenzcyclohepta-1,3-diene-6-one, 1. It was found that the isotope effects kH/kT and kD/kT for the faster exchanging protons (13.6 and 3.8 respectively) are significantly larger than the corresponding values for the slower exchanging protons (4.6 and 1.6 respectively). These differences could result from truly unequal isotope effects due to transition state differences or intrusion of a second pathway for exchange of the less reactive proton in the dedeuteration reaction. The data appear to support the latter interpretation. The secondary deuterium isotope effect was found to be 1.18.

Sterically Hindered Aromatic Compounds. VI. A Remote ε-Deuterium Kinetic Isotope Effect in the Solvolysis of Perdeutero-2,4,6-tri-tert-butylbenzyl Chloride

1975 ◽  
Vol 53 (21) ◽  
pp. 3171-3174 ◽  
Author(s):  
L. Ross C. Barclay ◽  
John R. Mercer ◽  
Peter J. MacAulay
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Aromatic Compounds ◽  
Kinetic Isotope Effect ◽  
Inductive Effect ◽  
Steric Effects ◽  
Deuterium Isotope Effect ◽  
Tert Butyl ◽  
Kinetic Isotope ◽  
Sterically Hindered

2,4,6-Tri-tert-butylbenzyl chloride deuterated at the three tert-butyl groups was synthesized. Conductimetric solvolysis studies of the normal and perdeutero-2,4,6-tri-tert-butylbenzyl chloride at 30.06 °C in 80% ethanol–water provides evidence for an inverse remote ε-deuterium isotope effect, kH/kD = 0.873−0.874. Under the same conditions the α-deuterium isotope effect was kH/kαD = 1.166 per deuterium, indicative of limiting solvolytic behavior. The remote ε-deuterium isotope effect for the perdeutero compound is discussed in terms of the inductive effect of deuterium and steric effects on the transition state conformation.

The Mechanism of The Microbial Hydroxylation of Steroids. Part 1. The C-21 Hydroxylation of Progesterone by Aspergillusniger ATCC 9142

1975 ◽  
Vol 53 (6) ◽  
pp. 845-854 ◽  
Author(s):  
Herbert L. Holland ◽  
Barbara J. Auret
Keyword(s):  
Hydrogen Bond ◽  
Carbonyl Group ◽  
Isotope Effect ◽  
Enol Form ◽  
Deuterium Isotope Effect ◽  
Rate Determining Step ◽  
Microbial Hydroxylation ◽  
Hydroxylation Reaction ◽  
Microbial C

The mechanism of the C-21 hydroxylation of progesterone (1a) by Aspergillusniger ATCC 9142 to give 11-deoxycorticosterone (1b) has been studied by the use of progesterone derivatives and of C-21 deuterium labelled progesterones. The requirement of the C-21 hydroxylase system for a C-20 carbonyl group is demonstrated and the possibility of the involvement of this group, in the C-20,21 enol form, in the C-21 hydroxylation reaction has been discussed. However, on the basis of the observed deuterium isotope effect (KH/KD = 1.25), a mechanism for the microbial C-21 hydroxylation reaction is proposed in which the rate-determining step is the direct insertion of oxygen into a C-21 carbon–hydrogen bond and not one involving enolization of the C-20 carbonyl.In addition, C-11α and C-15β hydroxylation of both 20α- and 20β-hydroxypregn-4-ene-3-one (2a and 2b) by A. niger has been observed.

Charge Development and Mechanism in Disrotatory Ring Opening of Cyclopropyl Bromides

1974 ◽  
Vol 52 (14) ◽  
pp. 2660-2665 ◽  
Author(s):  
Jan Han Ong ◽  
Ross Elmore Robertson
Keyword(s):  
Transition State ◽  
Temperature Dependence ◽  
Temperature Coefficient ◽  
Isotope Effect ◽  
Ring Opening ◽  
Deuterium Isotope Effect ◽  
Enthalpy Of Activation ◽  
Cis And Trans ◽  
Hydrolysis Of

The temperature dependence of the rates of hydrolysis of cis- and trans-2-vinylcyclopropyl bromides has been determined in water. The temperature coefficient of the enthalpy of activation (ΔCp≠) for both compounds was unusual (−27 and −35 cal mol−1 deg−1). From this fact, it was concluded that the charge development at the transition state was low, in agreement with the conclusions of Clark and Smale (19). The slightly inverse α-deuterium isotope effect (kH/kD = 0.994) is consistent with that conclusion.

The effect of steric crowding on an E2 transition state

1976 ◽  
Vol 54 (14) ◽  
pp. 2339-2341 ◽  
Author(s):  
George Stanley Dyson ◽  
Peter James Smith
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Nitrogen Isotope ◽  
Bond Rupture ◽  
Deuterium Isotope Effect ◽  
Steric Crowding ◽  
Reaction Proceeds ◽  
Hydrogen Deuterium ◽  
Nitrogen Bond ◽  
Mechanism Of The Reaction

The mechanism of the reaction of 9-(4-substituted benzyl)fluorene-9-trimethylammonium ions with ethoxide is a normal E2 process. The magnitude of the primary hydrogen–deuterium isotope effect at 60 °C increased with increasing electron-donating ability of the 4-substituent, i.e., 4.15, 5.10, 5.34, 5.65, 5.75, and 5.91 for the 4-CF3, 4-Br, 4-Cl, 4-H, 4-CH3, and 4-OCH3 substituents, respectively. The magnitude of the nitrogen isotope effect at 70 °C decreased with increased electron-donating power of the 4-substituent, i.e., [(k14/k15)–1]100 = 1.24, 0.95, 0.92, 0.91, and 0.80 for the 4-CF3, 4-F, 4-H, 4-CH3, and 4-OCH3 substituents, respectively. A small Hammett ρ value of +1.33 was observed for the reaction. It is concluded that the reaction proceeds via a transition state where the proton is more than one-half transferred to base. It is further concluded that for a reaction in which the 4-substituents decrease the rate, both carbon–hydrogen and carbon–nitrogen bond rupture is more advanced in the transition state. This variance with Hammond's postulate is discussed in the light of steric crowding at the transition state.

A Primary Hydrogen-Deuterium Isotope Effect Study on the Carbonyl Elimination Reaction of 9-Fluorenyl Nitrate with Various Bases

1975 ◽  
Vol 53 (2) ◽  
pp. 263-268 ◽  
Author(s):  
Peter James Smith ◽  
Lorraine Marion Noble
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Isotope Effects ◽  
Effect Study ◽  
Elimination Reaction ◽  
Deuterium Isotope Effect ◽  
Nitrogen Bases ◽  
Transition State Geometry ◽  
Hydrogen Deuterium ◽  
Deuterium Isotope Effects

The carbonyl elimination reaction of 9-fluorenyl nitrate with various nitrogen bases in anhydrous ethanol at 0 °C was examined. In all cases fluorenone was formed in 100% yield indicating that there was not any substitution. A reasonable Brønsted plot was obtained for reaction promoted by structurally similar bases with β = 0.84 which suggests a product-like transition state. As well, deviations from the Brønsted plot are discussed. Primary hydrogen-deuterium isotope effects were measured for reaction promoted by 11 different amine bases. A reasonable correlation was obtained for structurally similar bases when a plot of kH/kDvs. pKa was made. The conclusion is reached that when kH/kD reaches a maximum, ∼9.2 at 0 °C, it remains unchanged and hence is a poor measure of transition state geometry. As well, very poor correlations are found when the abstracting base is tertiary which leads to the conclusion that a comparison of kH/kD values is not warranted for structurally different bases.

The effect of the leaving group on the nature of the E2 transition state for reaction of 2-aryl-1-phenylethylammonium ions with ethoxide in ethanol

1981 ◽  
Vol 59 (20) ◽  
pp. 3016-3018 ◽  
Author(s):  
Shune-Long Wu ◽  
Peter James Smith
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Deuterium Isotope Effect ◽  
Significant Dependence ◽  
Leaving Group ◽  
Rate Of Reaction ◽  
Hydrogen Deuterium ◽  
Leaving Groups

The reaction of 2-aryl-1-phenylethylammonium salts with ethoxide in ethanol at 40 °C for five different amine leaving groups has been investigated. A significant dependence of the rate of reaction on the basicity of the leaving group was found. The variation of the primary hydrogen–deuterium isotope effect and pKa of the leaving group was not linear and it is concluded that the proton is less than one-half transferred to base at the transition state for reactions involving the best two leaving groups. In support of this conclusion is the observed opposite variation of kH/kD with ring substituents for the various leaving groups, i.e., for N-methylpyrrolidine, kH/kD = 4.58, 4.72, and 5.01 for p-Me, H, and p-Cl, respectively; for N-methylmorpholine, kH/kD = 6.13, 5.73, and 5.50 for p-Me, H, and p-Cl, respectively.

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