Reactions involving two proton transfers

The results of the above analysis of reactions involving two proton transfers may be compared with those for reactions in which only a single transfer is kinetically relevant (Sec. III.3.a). For a single transfer the existence of an equilibrium between catalyst and substrate always produces the appearance of specific catalysis by hydrogen or hydroxyl ions, and the detection of general acid-base catalysis therefore excludes... 

In the above treatment it has been assumed that the ions (HRH)+ and Br exist in the free state, as they undoubtedly do in aqueous solution. However, solvents which are aprotic, e.g., hydrocarbons, normally have such low dielectric constants that the majority of ions present will exist at least as ion pairs, and partly as larger aggregates. This circumstance may well affect the kinetics. For a reaction involving only a single proton transfer the concentration of ion pair will be directly proportional to the concentrations of catalyst and substrate, so that the kinetics will be simpler than when free ions are present. On the other hand, in reactions involving two proton transfers, if the first product of... 

We must now consider the kinetic analysis of catalysed reactions involving two proton transfers. These include the so-called prototropic isomerizations, notably keto-enol tautomerism. The simplest mechanisms for catalysis by acids and bases are as follows ... 

Similar considerations apply to reactions involving two proton transfers in aprotic solvents. If the first step is rate-determining, the problem reduces to a single proton transfer. When the second step is ratedetermining, the assumption of free ions leads to the same prediction as in aqueous solution, since the composition of the transition state is still equivalent to one molecule of substrate plus one molecule of acid, and this remains true even if the ions HSH and B" are associated in a pair. However, the ion pair initially formed in the first proton transfer may well have a configuration which is unfavourable for the second proton transfer, which involves the removal of a proton from a different atom. This raises the possibility that the second proton transfer may involve another basic... 

This reaction involves two proton transfer steps—one before and one after the Sn2 attack— as seen in Mechanism 7.2. 

Bronsted acid/base catalysis is the most common enzymatic mechanism, since nearly all enzymatic reactions involve a proton transfer. This means that nearly all enzymes have acidic and/or basic groups in their active site. In add catalysis, the substrate is protonated by one of the amino add residues at the active site (typically aspartic acid, glutamic acid, histidine, cysteine, lysine, or tyrosine). This residue itself must therefore be protonated at the readion pH (typically between pH 5 and 9), with a pKa just above this value. Conversely, in base catalysis, the pJCa of the deprotonating residue must be just below the physiological pH. Some enzymes can even carry out bifunctional catalysis, by protonating and deprotonating two different sites on the same substrate molecule simultaneously. 

Reaction of (COD)2Ni with acetylacetone (73) produces orange crystalline 7r-(4-cyclooctenyl)acetylacetonatonickel(II) which sublimes in vacuo at about 60°C and melts with decomposition at 75°C. The reaction involves a proton transfer from acetylacetone to the COD ring with a concomitant change of the nickel oxidation number from zero to two. A structural analysis (412) has shown an essentially square planar coordination about the nickel (Fig. 4) with a C=C length of 1.42 A and a Ni-C distance of 2.03 A, [these values are very close to those observed for the complex (C2H4)Ni[P(C,iH5)3].2 (122)], and a Ni CH, distance of 1.95 A. 

The proton transfer may occur rapidly after the excitation and form a tautomer, when either acidic or basic moieties of the same molecule become stronger acids or bases in the excited state. The majority of reactions of this type involve the proton transfer from an oxygen donor to an oxygen or nitrogen acceptor, although a few other cases are known, where a nitrogen atom can function as a donor and a carbon atom as the acceptor. Usually an intramolecular hydrogen bond between the two moieties of a molecule facilitates the proton transfer. 

Metal deposition is an example of a more general class of electrochemical reactions, ion transfer reactions. In these an ion, e.g. a proton or a chloride ion, is transferred from the solution to the electrode surface, where it is subsequently discharged. Many ion-transfer reactions involve two steps. The hydrogen-evolution reaction, for example, sometimes proceeds in the following way ... 

Mechanistically speaking there have been no recent advances. What is known is that, at least for 4-OH formation, the reaction is intermolecular, requires two proton transfers at some stage and that a symmetrical intermediate is involved (often described as... 

The mechanisms of two other reactions described in Sect. 2.2 involve slow proton transfer to unsaturated carbon. The general acid catalysed cleavage of vinyl mercuric halides [42, 50] for example, allyl mercuric iodide, CH2=CHCH2HgI (XXII), gives Bronsted exponents around 0.7. Linear Bronsted plots are obtained with carboxylic acid catalysts but, as observed in other A—SE 2 reactions, general acids of different structural types (for example, hydronium ion or bisulphate ion) show substantial deviations. Bronsted catalysis of the hydrolysis of diazo compounds (N2 =CR X) has been studied by the groups of Albery and Kreevoy. With... 

Two possible mechanisms for methanol oxidation by MDH enzymes have been proposed in the literature, the Addition-Elimination (A-E) and the Hydride Transfer (H-T) mechan-isms. " The A-E is a three-step mechanism (Fig. 2a) that involves a proton transfer from methanol to an active site base, which is proposed to be ASP303. It is believed that the presence of this catalytic base at the MDH active site initiates the oxidation reactions by subtracting a proton (H16) from methanol (Fig. 2a). This proton addition to ASP303 leads to the formation of a covalent hemiketal intermediate, since the resulting oxyanion (016 ) in the methanol molecule is then attracted to the C5 of PQQ. The second step consists of the proton (H16) elimination from ASP303 and transfer to 05 of PQQ, and the final step is characterized by a... 

First, the enzyme has at least two and probably three active-site basic groups involved in proton transfers to and from substrates, intermediates, and nascent products and all three bases are located on the si face of the substrate-PLP aldimine system as are the protons to be shuffled about, so all the proton transfers are likely to be economically suprafacial. Several pieces of stereochemical evidence suggest that the j5,y-olefinic PLP-p-quinoidal-a-anion (141) can rotate around its C(P)-C(ol) bond and also implicate that the cisoid isomer of this n complex and then the Z-isomer of the nascent aminocrotonate carry 80 % of the reaction flux. Furthermore, a 15% internal retention of the from the Pro-R methylene of ACPC (9) on B2H (85 % exchange with solvent, 15 % internal return) in the active site and the overall 22/78 H /H5 distribution at C(3) of the mono- and dideutero 2-ketobutyrate (138) products at C(3) are also noted. 

If we find experimentally kD > kH in a catalyzed reaction, then an acid-base equilibrium must always be involved in the kinetic scheme. If the reaction involves only one proton transfer, then the converse is also true for catalysis by hydrogen ions, i.e., if kB > fcD, then there is no pre-equilibrium. On the other hand, in a reaction involving two successive proton transfers the pre-equilibrium and the subsequent proton... 

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