Effects in Mechanistic Studies

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 

Examination of the magnitude of an H/D isotope effect in appropriate cases usually enables a distinction to be made between an equilibrium or a rate-determining protonation step. It may also be useful in distinguishing between the electrochemical hydrogenation pathway and the electron transfer/fast protonation pathways in cathodic reduction at metals of intermediate hydrogen overvoltage and moderate affinity for H (Cu, Ag, W contrast Ni, Pt, Rh). Correspondingly, oxidations, e.g., of hydrocarbons and derivatives 

Cases of this kind have been investigated in studies of anodic hydrocarbon oxidation/ While a priori calculations of the values of electrochemical kinetic Isotope effects, particularly with complex organic molecules, cannot be regarded as quantitatively reliable owing to the difficulty of evaluation of the relevant reactant and transition state partition functions for particles in solution, nevertheless sufficient experimental data exist which, coupled with theoretical evidence of trends of values of the isotope effect for different types of reaction pathway, enable useful distinctions in mechanism to be made on the basis of H/D kinetic isotope experiments on electrochemical reactions. 

In this class of reaction, ° an initial dissociative chemisorption step occurs in which the molecule is split, usually into adsorbed H and adsorbed carbonaceous fragments, which are subsequently electrochemically oxidized either directly, as with H (MH M + + e), or indirectly, as with the 

The simplest model reaction for the electrocatalytic type of electro organic reaction is really that of H2 at catalytic noble metals, especially Pt. 

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The use of secondary deuterium kinetic isotope effects in mechanistic studies of olefin bromination... 

Despite the complexity (discussed earlier) in the quantitative interpretation of photoluminescence measurements, they proved to be very effective in mechanistic studies of OLED degradation. A seminal work by Aziz, Popovic, and coworkers demonstrated that Alq cation-radicals are unstable in a solid-state, OLED-like environment [62]. They designed mostly monopolar devices to study the separate effects of charge carriers on the stability of Alq. 

What concerns us here are three topics addressing the fates of bromonium ions in solution and details of the mechanism for the addition reaction. In what follows, we will discuss the x-ray structure of the world s only known stable bromonium ion, that of adamantylideneadamantane, (Ad-Ad, 1) and show that it is capable of an extremely rapid degenerate transfer of Br+ in solution to an acceptor olefin. Second, we will discuss the use of secondary a-deuterium kinetic isotope effects (DKie) in mechanistic studies of the addition of Br2 to various deuterated cyclohexenes 2,2. Finally, we will explore the possibility of whether a bromonium ion, generated in solution from the solvolysis of traAU -2-bromo-l-[(trifluoromethanesulfonyl)oxy]cyclohexane 4, can be captured by Br on the Br+ of the bromonium ion, thereby generating olefin and Br2. This process would be... 

Apart from a few studies (ref. 7), the use of deuterium kinetic isotope effects (kie s) appears to have had limited use in mechanistic studies of electrophilic bromination of olefins. Secondary alpha D-kie s have been reported for two cases, trans-stilbene fi and p-substituted a-d-styrenes 2, these giving relatively small inverse kie s of... 

Rettie AE, Boberg M, Rettenmeier AW, et al. Cytochrome P-450-catalyzed desaturation of valproic acid in vitro. Species differences, induction effects, and mechanistic studies. J Biol Chem 1988 263(27) 13733-13738. 

On the positive side it is important to note that primary isotope effects are only observed when the bond concerned is undergoing rupture in the rate determining step of a reactionx. Thus, the effect is of paramount importance in mechanistic studies for the identification of rate determining steps. Two examples illustrate the point a) Chain transfer in styrene polymerization (75)... 

The application of correlation analysis of solvent effects to mechanistic studies of solvolysis has been reviewed by Takeuchi in Japanese.110 The article mainly covers die behaviour of tertiary chloro compounds. Tins author s research group has continued experimental studies in this area.111-113 Rates of solvolysis of 2-chloro-2,4-trimethylpentane have been measured in 17 solvents and analysed through the extended Grunwald-Winstein equation, which includes a term for nucleophilic participation.111... 

The above results emphasise the value of product selectivities in mechanistic studies, but also show that reaction mechanisms can change as substituents and/or solvents are varied. Consequently, when the kinetic effects of substituents and solvents are used to probe reaction mechanisms, the possibility that the probe induces a mechanistic change should be considered. 

Such effects are confined to reactions in solution, and are of fundamental importance in mechanistic studies. As with entropy changes, there are several factors which can make a substantial contribution to the overall AV. ... 

Since it is well established that the P-chiral phosphorothio-ates serve as effective probes in mechanistic studies for the phos-phoryl group transfer enzymes /16/, we turned our attention to the application of diastereomeric 8 (B=Thy, Ar=pN02C6Hi -,/17f) to elucidate the mode of action of spleen phosphodiesterase (SPDE, EC 3.1.1. 18). This enzyme splits the phosphodiester bonds to yield nucleoside 3 -phosphates. In the case of it was expected that its SPDE-catalyzed hydrolysis in 180 H 2O medium leads to P-chiral thymidine 3 - 180 phosphorothioate. On the contrary to our expectation the main product of this reaction was thymidine cyclic 3 ,5 - Rp phosphorothioate (10) /6/. By treatment of 8 under the same conditions, but in the absence of the enzyme, no trace of J 0 was detected. ... 

Of course, it can also be argued that if a transfer effect is expressible by including in the relevant equation factors of the form of equation (118), then such a chemically definite model of the transfer effect amounts to a more complete statement of the reaction mechanism. To that extent, therefore, the border line between exchange and transfer effects in mechanistic solvent isotope effect studies becomes shrouded in semantics. 

Taking into consideration the agreement between experimental and predicted isotope effects, in the case of the aliphatic Claisen the best transition state is represented by the MP4/6-31G structure. For both aliphatic and aromatic rearrangements the transition states are intermediate between the B3LYP/6-31G and the MP2/6-31G structures. This publication is a valuable guide in application of KIEs in mechanistic studies. 

While good <5ES correlations within a-substituted series were found in mechanistic studies, the reason for nonapplicability of Es parameters to a / -series in the quaternization of thiazoles was not experimentally determined. There are two possible reasons for this nonapplicability. (1) The Taft Es parameters are not solely a measure of steric effects, but rather also contain inductive, resonance, and other effects and must be corrected and more precisely redefined. (2) The Taft Es parameters do measure steric effects, but,... 

The use of DMSO as a mechanistic tool is not restricted to rate variation effects (Section 4). Advantage can also be taken of its unique molecular properties which enable it to stabilize certain types of structures, such as the anionic intermediates in SnAt reactions. Moreover, as a consequence of its influence on ion association constants, it is found to affect the product distribution and the stereochemical course of bimolecular olefin-forming eliminations. These two illustrative systems which have been chosen for discussion are intended to demonstrate the versality of this solvent in mechanistic studies and may suggest other avenues of investigation. 

Recent data regarding the action of low-level mercury exposure on receptors and signal transduction pathways in peripheral lymphocytes suggest potential applications of certain surrogate markers in mechanistic studies of neurotoxicity and, possibly, in assessing early biochemical effects of neurotoxicants in humans (Manzo et al. 1995). Additional biomarkers for effects on the immune, renal,... 

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