Indirect Proton Transfer

One method has been proposed for testing the n = 0 model for monobasic acids (Kreevoy, 1965b). That involves the relation between kkaIkda (defined in Section IIA3) and ha/ da- If the n = 0 mechanism is correct, and if there are no isotope effects other than the primary isotope effect, kha/ da is given by equation (54). To test this equation 

Reaction Acid LBaO IjJitO kRA / DA KJ a0TOa° (kha/kha)0 10 (KHA/KDA)°b Reference 

Allylmercuric iodide cleavage HS07 8-0 1-38 11-0 8-1 Kreevoy and Straub, 

Ethyl vinyl ether hydrolysis cich2co2h 6-2 1-05 6-5 5-2 Kreevoy and Eliason, unpublished data 

Similar conclusions have been reached by Albery (1967) who has examined this problem in great detail. 

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The expansion in the power of computers and theoretical methods has made it possible to investigate the mechanism of action of enzymes by combinations of quantum-mechanical and molecular-mechanical calculations. A study of two possible mechanisms for dihydrofolate reductase catalysis was consistent with indirect proton transfer from aspartate to N-5 of the pterin as has been suggested for many years by crystallographic evidence <2003PCB14036>. This conclusion is also consistent with the outcome of a study that directly measured the of the active site aspartate in the Lactobacillus casei enzyme <1999B8038>. Observations of chemical shifts of... 

The transamination reaction involves three sequential steps (i) formation of a tetrahedral intermediate with the active site lysine and the amino substrate bonded to the PLP cofactor (ii) indirect proton transfer between the amino substrate and the lysine residue and (iii) formation of the external aldimine after the dissociation of the lysine residue (Figure 1.31) [32,33]. 

Hydrogen Abstra.ction. These important reactions have been carried out using a variety of substrates. In general, the reactions involve the removal of hydrogen either direcdy as a hydrogen atom or indirectly by electron transfer followed by proton transfer. The products are derived from ground-state reactions. For example, chlorarul probably reacts with cycloheptatrienyl radicals to produce ether (50) (39). This chemistry contrasts with the ground-state reaction in which DDQ produces tropyhum quinolate in 91% yield (40). 

Rate coefficients for direct (/cd) and indirect (/tj) proton transfer for amines , , ... 

The free-radicals are generated by discharge of proton, peroxides and easily reducible compounds at the cathode according to Eq. (1—4). The radial-anion of monomer is obtained by both direct and indirect electron transfer process [Eq. (5—6)]. The indirect process means that the active oxidizing species is formed from the electrolytes by electrode reaction, followed by interaction with the monomer. An unstable monomer like a,a -2-trichloro-p-xylene is formed and polymerizes instantaneously [Eq. (7)]. The regeneration of ferrous ion from the pool of used up ferric ion in a redox system is electrolytically successful [Eq. (8)] and an... 

Though the proton transfer of the keto enol equilibrium is only indirectly related to... 

A frequently used indirect method involves cyclizable (cf. (7)) or other mechanistic probes which should provide evidence for free radical intermediates and thus for SET [19,37,59]. However, Newcomb and Curran have pointed out the pitfalls of such an approach especially if iodide precursors are used [17]. The supposedly radical-indicative reaction may come about albeit slower by a different, nonradical mechanism or the radical formation may occur via a secondary process which is not directly related to the first reaction step. A similar side-route can be made responsible for the appearance of stable radical compounds which may arise via a comproportionation reaction between non-reduced starting material and the doubly reduced species which can be formed from a hydro form (the normal product, Eq. (5)) and the usually strongly basic organometallic or hydridic reagents (Eq. (9)) [58]. The ability of strong bases to produce reduced radical species via complicated electron/proton transfer processes has been known for some time in the chemistry of quinones and quaternary salts [60,61]. 

Aminyl radicals have also been detected indirectly during the reaction of hydroxyl radicals (HO ) or their conjugated base ( 0 ) with the free amino group of amino acids (Reactions (3.9) and (3.10)) [40-43], and identified by time-resolved EPR experiments [44]. Similar reactions may be expected for peptides. While Reactions (3.9) and (3.10) show a net hydrogen transfer, they likely proceed via a stepwise electron-transfer and proton-transfer (Reaction (3.11)), a reaction commonly referred to as proton-coupled electron transfer (PCET). Proton transfer from the ami-nium radical cation to the base (OH ) will likely occur within the solvent cage. 

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