Displacement reactions product dissociation rates

Thus, the main cause of perturbation of p/Ca values in the V profiles is the fact that the chemical reaction is not rate-limiting. However, when the stickiness of a substrate does not displace the pK a values in V profiles, it can lead to more complex shapes than the simple one corresponding in algebraic form to equation = (V /i )/(i-i-H /i a)i if proton access to the groups involved is restricted in the central productive complex of enzyme wiA substrates. When both the substrate that dissociates most rapidly from the central complex and the proton on the group in question are sticl, the curve will have a hollow in the vicinity of the pK. ... 

This simply explains the occurrence of a primary isotope rate effect, "primary" referring to the fact that the rate determining step involves a bond to the isotopically substituted atom. However, many reactions which show large primary isotope effects do not involve dissociation into free particles but rather are displacement reactions wherein the isotopic atom is abstracted by an attacking agent. Since the isotopic atom is bound both in reactant and product and is bound also in the transition state, how can the occurrence of large isotope effects in such processes be explained ... 

These present an interesting dichotomy in their reductions by tm(l,10-phen-anthroline)iron(ri) (ferroin) °. That of CIO2 to CIOJ is rapid, is first-order in each component ki = 1.86 0.13 l.mole sec at 35 °C) and is independent of acidity. Ferriin is the immediate product and an outer sphere electron-transfer is proposed. The reduction of CIO2 is much slower, proceeding at the same rate as dissociation of ferroin at high chlorite concentrations and a major product is feriin dimer, possibly [(phen)2Fe-0-Fe(phen)2] . Clearly the reaction depends on ligand-displacement followed by an inner-sphere electron transfer. 

The intermediate reaction complexes (after formation with rate constant, fc,), can undergo unimolecular dissociation ( , ) back to the original reactants, collisional stabilization (ks) via a third body, and intermolecular reaction (kT) to form stable products HC0j(H20)m with the concomitant displacement of water molecules. The experimentally measured rate constant, kexp, can be related to the rate constants of the elementary steps by the following equation, through the use of a steady-state approximation on 0H (H20)nC02 ... 

Rates for this reaction may easily be measured by disappearance of azide UV absorption. Most importantly, kinetic saturation behavior is noted with sufficient amounts of the reactants cycloaddition velocity becomes independent of substrate concentration. As is familiar from enzyme catalysis, this indicates complete occupancy of all available cucurbituril by reacting species. In actuality, the rate of the catalyzed reaction under conditions of saturation was found to be the same as that for release of the product from cucurbituril. Such a stoichiometric triazole complex was independently prepared and its kinetics of dissociation were examined by the displacement technique previously outlined, giving the identical rate constant of 1.7xl0 s under the standard conditions. (It is not uncommon for product release to be rate-limiting in enzymic reactions). 

The reactions of the pentaamminecobalt(III) complex of urea (O-coordinated) have also been studied.506 Under basic conditions [Co(NH3)5OH]2+ is the only cobalt(III) product. The main reaction pathway (ca. 97%) is SN1CB displacement of coordinated urea (Scheme 40) with kOH = 15.3 M s-1 at 25 °C. A limiting rate was approached at high pH as the complex dissociated to its inactive conjugate base. Hydrolysis of coordinated urea was not observed. 

If the substrate is sticky (i.e., dissociates more slowly than it reacts to give products), the plQ values will not be seen in the correct position on the profile, but will be displaced outward (i.e., to lower pH when protonation decreases activity, and to higher pH when protonation increases V/K). The amount of displacement will be Iog(i + k /kz), where is the net rate constant for reaction of the collision complex to yield products, and is for dissociation. With a sticky substrate, the displacement can be a pH unit or more, although values of 0.5-1.0 pH unit are more common. 

While the displacement of the plC is a sufficient problem, a further difficulty with sticky substrates is the alteration in shape of the pH profile in the vicinity of pJEa. which can occur with certain values of the rate constants. This alteration in shape can take the form of a hoUow, and very infrequently a form of a hump. The hollow in the pH profile results when proton movement into and out of the active site is restricted, so that the state of protonation of the enzyme-substrate complex is not equiUbrated rapidly with respect to the rate of reaction to give products or the rate of substrate dissociation (Section 14.4). 

Not shown in the description above, but assumed to be important, is solvation at the rear side of in the ion pairs. According to this scheme, attack by a nucleophile or solvent can occur on the covalent substrate, the intimate ion pair, the solvent-separated ion pair, or on the dissociated carbonium ion. Nucleophilic attack on the covalent substrate or on the intimate ion pair will be akin to a displacement process, and will take place with inversion of configuration. At the solvent-separated ion-pair stage, collapse of the solvent shell can occur from the front to produce retention of configuration or from the back to produce inversion, or the carbonium ion can become symmetrically solvated to produce racemic product. The macroscopic properties of the nucleophilic substitution reaction result from competition among these various rate processes. 

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