Secondary kinetic isotope effect participation

Kinetic isotope effect for lysozyme. A secondary kinetic isotope effect is expected because a molecule with H in the number 1 position can be converted to the corresponding oxocarbenium ion somewhat more easily than the molecule with 2H in the same position (Eq. 12-13). For example, in the nonenzymatic acid-catalyzed hydrolysis of a methyl- glucoside, a reaction also believed to proceed through a carbocation intermediate,41 75 the ratio h / h, is 1.14 for the a anorner and 1.09 for the (3 anorner.53 In the base-catalyzed hydrolysis of the same compound, which is believed to occur by a double-displacement reaction involving participation of the neighboring OH group on C-2, the ratio /c1h / /c2h is 1.03. The corresponding ratio measured... 

Sialosides have a distinct mechanism of hydrolysis for its unusual sugar structure of sialic acid. For example, the large 8-dideuterium and small primary kinetic isotope effects observed at the anomeric carhon and the large secondary kinetic isotope effect observed at the carboxylate carbon in the acid-catalyzed solvolysis of CMP-Af-acetyl neuraminate 24 support an oxocarbenium ion-like transition state 25 having the 5S conformation without nucleophilic participation of carboxylate and with the carboxylate anion in a looser environment than in the ground state [15] (O Fig. 3). Such a zwitterion structure is consistent with the results from calculations using the COSMO-AMI method for aqueous solutions [16]. 

Primary and secondary kinetic isotope effects are of general importance in the study of neighboring group participation. Isotopic substitution a to the incipient carbo-cation produces a secondary isotope effect whereas 0 and y substituents may give rise to both primary and secondary effects. For example, if the rate determining step of a solvolytic reaction involves a hydrogen shift or elimination, primary deuterium isotope effects are clearly implicated. 

Resume. Alkyl participation in the solvolysis of exo-2-norbornyl derivatives is not unambiguously detected by rate measurements. Neither monocyclic analogs nor the corresponding enr/o-2-norbornyl compounds appear to be good models for comparison. Secondary deuterium kinetic isotope effects, however, point to distinct ionization mechanisms of exo- and -norbornyl derivatives. 

The only isotope effects which are usually of significance in electroorganic mechanism considerations are those involving H and D in (a) primary kinetic isotope effects, (b) secondary solvent isotope effects where reactions are compared in pure H2O and D2O or pure h- and rf-alcohols, and (c) in prior protonation equilibria, e.g., with ketone reduction. Primary kinetic isotope effects having a magnitude of > 2.5 may be expected in reactions that involve a rearrangement with proton participation, e.g., keto-enol tautomerism prior to an electron transfer step. Most other H/D isotope effects arise from protonation equilibria prior to the rate-controlling electron transfer step (e.g., in ketone reduction RR CO + RR COH ) and the isotope effect is... 

This study on the kinetic chlorine isotope effect in ethyl chloride50 was extended to secondary and tertiary alkyl halides pyrolyses51. The isotope effects on isopropyl chloride and terf-butyl chloride pyrolysis were found to be primary and exhibited a definite dependence on temperature. They increased with increasing methyl substitution on the central carbon atom. The pyrolysis results and model calculations implied that all alkyl chlorides involve the same type of activated complex. The C—Cl bond is not completely broken in the activated complex, yet the chlorine participation involves a combination of bending and stretching modes. 

An alternative proposal for the transition state of the ene reaction involving carbonyl groups, specifically mesoxalic esters, has been advanced. On the basis of little variation in the primary kinetic deuterium isotope effect (2.55 at 120 nC and 2.58 at 200 °C) it was concluded that the transition state involved a C-H-O arrangement significantly distorted from linear and involving participation of a lone-pair of electrons on oxygen as well as secondary orbital overlap7,8. 

An observed small isotope effect may also arise from a secondary isotope effect. Such effects occur when the isotope is attached to, or near, an atom which is participating in bond breaking. These secondary isotope effects result from changes in the vibrational force constants of the isotopic atom as the reaction proceeds to the transition state and may account for h/ d values as large as 1.74 (9). Thus only Ah/ d values above 2.0 may be safely attributed to a primary isotope effect for a single deuterium substitution. The contribution which each of these effects makes to an overall small isotope effect can be evaluated by sophisticated kinetic techniques (7, 10). 

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