Effect on hydrolysis reactions

There are a few documented examples of studies of ligand effects on hydrolysis reactions. Angelici et al." investigated the effect of a number of multidentate ligands on the copper(II) ion-catalysed hydrolysis of coordinated amino acid esters. The equilibrium constant for binding of the ester and the rate constant for the hydrolysis of the resulting complex both decrease in the presence of ligands. Similar conclusions have been reached by Hay and Morris, who studied the effect of ethylenediamine... 

Typical solvent isotope effects on hydrolysis reactions... 

Certain complexes of cobalt were reported (10, 11) to have catalytic effects on hydrolysis reactions. 

Cosolute effects on hydrolysis reactions in water-rich aqueous media can be examined quantitatively by using a combined thermodynamic and kinetic analysis. The background theory shows that... 

Next to the temperature, the water/PET ratio has the strongest effect on hydrolysis reactions. An initial water/PET ratio (w/w) of 5.1 [8] and 6 [7,9] was found to be necessary for a complete hydrolysis between 265°C and 270°C. Below this water concentration, an equilibrium is established (Table 2). The data for the equilibrium constant K differ strongly between the experimental set-ups. However, a reduction of K with increasing temperature was... 

The observation of a primary solvent deuterium isotope effect (kH/fa>) = 2-4 on the specific acid-catalyzed hydrolysis of vinyl ethers provides evidence for reaction by rate-determining protonation of the alkene.69 Values of kHikD 1 are expected if alkene hydration proceeds by rate-determining addition of solvent to an oxocarbenium ion intermediate, since there is no motion of a solvent hydron at the transition state for this step. However, in the latter case, determination of the solvent isotope effect on the reaction of the fully protonated substrate is complicated by the competing exchange of deuterium from solvent into substrate (see above). 

Ab initio SCRF/MO methods have been applied to the hydrolysis and methanol-ysis of methanesulfonyl chloride (334). ° The aminolysis by aromatic amines of sulfonyl and acyl chlorides has been examined in terms of solvent parameters, the former being the more solvent-dependent process.Solvent effects on the reactions of dansyl chloride (335) with substituted pyridines in MeOH-MeCN were studied using two parameters of Taft s solvatochromatic correlation and four parameters of the Kirkwood-Onsager, Parker, Marcus and Hildebrand equations. MeCN solvent molecules accelerate charge separation of the reactants and stabilize the transition... 

Structural modifications of the drug may be employed to retard hydrolysis. The most frequently encountered hydrolysis reaction involves the ester. Substituents can have an effect on these reaction rates. Flansch and Taft [14] and Hammett [15] provide excellent reviews of the topic. Additionally, a compound may be stabilized by reducing its solubility. This can be accomplished by the addition of lipophilic substituents to side chains or aromatic rings. Often less soluble salts or esters have been employed to aid in product stability. 

Remarkably, the presence of water showed beneficial effects on both reaction rates and selectivities, while facilitating the iminium ion hydrolysis step in the catalytic cycle. Computational studies suggest an asynchronous mechanism for the reaction [23-25], where the attack of the diene to the / -carbon atom of the iminium ion is the rate-limiting step [23], and the 7r,7r-interaction between the phenyl ring of the catalyst s benzyl group and the olefinic 7r-system of the iminium ion accounts for the selectivity of the reaction [6, 24]. 

Increasingly sophisticated catalytic domains have been synthesized and used as adducts to the framework polymers. These synthetic macromolecules show substantially enhanced catalytic effects on hydrolytic reactions, decarboxylation, Schiffbase hydrolysis, aromatic nucleophilic substitution, and oxidation [63-69]. Several of these synthetic polymers are effective peptidases and nucleases. 

The other point that was discovered was that some reaction rates were accelerated by operating in a mixed solvent rather than in pure water. The one that was examined most carefully was the acetyl transfer from bound ra-f-butylphenyl acetate to /3-cyclodextrin with buffers that in water give a pH of 9.5. It was observed that the reaction was almost 50-fold accelerated in a 60% DMS0-H20 solvent compared with the reaction rate in pure water. Part of this acceleration came from an increase in the apparent basicity of the medium, since relative pK s are solvent dependent part of it was also a solvent effect on the reaction rate of the cyclodextrin anion with the substrate. Thus, in 60% DMSO-H20 the /3-cyclodextrin reaction with this substrate was 13,000-fold faster than was the rate of hydrolysis of the substrate in an aqueous buffer of the same composition. Of this approximately 50-fold acceleration over cyclodextrin in water, about 10-fold was caused by changes in the pK s in the system and about 5-fold was caused by a change in the reaction rate of the cyclodextrin. 

---