Salt Effects on Solvolysis Reactions of p-Nitrophenyl Alkanoates Catalyzed by 4-(Dialkylamino)pyridine- Functionalized Polymer in Buffered Water and Aqueous Methanol Solutions

Abstract

Specific salting-in effects that lead to striking substrate selectivity were observed for the hydrolysis of p-nitrophenyl alkanoates 2 (n = 2−16) catalyzed by 4-(dialkylamino)pyridine-functionalized polymer 1 in aqueous Tris buffer solution at pH 8.0 and 30 °C. Macromolecule 1 was found to exhibit clear substrate preference for 2 (n = 6) in 0.05 M aqueous Tris buffer solution, as contrasted with the corresponding reaction in 0.05 M aqueous phosphate or borate buffer solutions where the substrate selectivity is absent. The formation of a reactive catalyst−substrate complex, 1·2, appears to be promoted by the presence of tris(hydroxymethyl)methylammonium ion, an efficient salting-in agent, from the Tris buffer system. The salting-in effect on formation of 1·2 complex is presumed responsible for the substrate specificity. The salting-out effects of sodium chloride on the solvolysis of 2 catalyzed by 1 were also investigated in 1:1 (v/v) methanol−water solution at pH 8.0 and 30 °C. The rate of 1-catalyzed solvolysis of 2 (n = 10−16) was found to vary inversely with NaCl concentration (0−1.0 M). The magnitude of the salting-out effects is dependent on the alkyl chain length in 2 and the concentrations of 1 and NaCl. At 7.5 × 10-5 unit mol L-1 1 and 0−1.0 M NaCl the order of reactivity for 2 (n = 10−16) was n = 10 > 12 > 14 > 16. However, at 5.0 × 10-6 unit mol L-1 1, a revised reactivity order, 2, n = 14 > 12 > 16, was obtained at [NaCl] < 0.15 M. A significant decrease in the substrate preference for 1-catalyzed solvolysis of 2 (n = 10−16) was observed at higher NaCl concentrations. We suggest that the reduced catalytic efficiency and selectivity expressed by 1 in the presence of sodium chloride should be attributed to changes in the morphology and composition of aggregates containing 1 and 2 in aqueous methanol solution that lead to decreased dependence of aggregate formation on the hydrophobicity of the substrate.

Ion‐Induced Specificity Change in Polymer‐Catalyzed Solvolyses of p‐Nitrophenyl Alkanoates

“…[~ -"1 We have reported that macromolecule 1 containing the 4-(dialkylamino)pyridine functionality and a bis(trimethy1ene)disiloxane backbone as a nucleophilic catalyst exhibits enzyme-like substrate selectivity for the solvolysis of 2 in aqueous and methanol/ water solutions.[". 13,14] To our knowledge, ion-induced substrate specificity changes have not been reported previously for catalytic ester solvolysis.…”

Control of Substrate Specificity in Polymer-Catalyzed Solvolysis Reactions of p-Nitrophenyl Alkanoates by Changing the Buffer System

“…Macromolecule 1 is an amphiphilic polymer which contains distinct hydrophobic and hydrophilic regions, and it associates to form macromolecular aggregates by self-assembly in aqueous or methanol−water solution. − The control of aggregate morphology changes of small-molecule and macromolecular amphiphiles from spheres to rods, and to vesicles by increasing the hydrophobic effects in water and water−organic solvent mixtures has already been well-established. − For many years, the aggregate morphology changes of small-molecule amphiphiles from spherical micelles to micellar rods and vesicles have been known to be controlled by increases of their constituent concentrations in solution. − The gradual changes of aggregate morphology of polystyrene- b -poly(2-vinylpyridine) copolymers from spheres to rods, and to vesicles have also been demonstrated with increasing copolymer concentration . Consistent with the notion that salt-induced hydrophobic effects control aggregate morphology of amphiphiles, the aggregate morphology of these copolymers in water−organic solvent mixtures can also be changed from spheres to rods, and to vesicles by addition of salting-out agents such as NaCl and CaCl 2 .…”

“…The addition of salting-out agent NaCl leads to a change of substrate specificity from 2 ( n = 14) to 2 ( n = 12) in 1:1 (v/v) methanol−aqueous phosphate buffer solution , Moreover, we have reported an interesting example of electrostatic interactions that contribute to the catalytic activity and substrate specificity for the 1 -catalyzed solvolysis of 2 ( n = 2−18) in the presence of anionic surfactant sodium dodecyl sulfate (SDS), which provides significant insight into the mechanism of catalytic ester solvolysis. These results may be akin to the observations that many enzymes usually accelerate the hydrolytic reactions at hydrophobic binding sites by electrostatic stabilization of the transition state through interactions with nearby amino acid constituents. , To our knowledge, the control of substrate specificity by changing the buffer system has not yet been reported for catalysis of solvolysis reactions of p -nitrophenyl esters.…”

“…4-(Dialkylamino)pyridine-functionalized polymers have been regarded as useful and simple model systems for obtaining a better understanding of the origins of enzymic efficiency and selectivity. − We have recently made an attempt to investigate such a model system to gain insight into the dominant control factors in solvolysis of p -nitrophenyl esters 2 ( n = 2−18) catalyzed by 4-(dialkylamino)pyridine-functionalized polymer 1 . − The mechanism of the reaction involves the attack by nucleophile 1 at the carbonyl group of substrates 2 and the formation of an N -acylpyridinium intermediate where the breakdown of the intermediate is the rate-determining step in the catalytic reactions . Strikingly, we have found ion-induced substrate specificity in the 1 -catalyzed solvolysis of 2 ( n = 2−18) in aqueous and methanol−water solutions. , Salting-in effects of the tris(hydroxymethyl)methylammonium ion in aqueous Tris buffer solution lead to the same substrate specificity for 2 ( n = 6) that is obtained with the enzyme, cholesterol esterase, for the same hydrolysis reaction …”

Effects of Surfactants on Solvolysis of p-Nitrophenyl Alkanoates Catalyzed by 4-(Dialkylamino)pyridine-Functionalized Polymer in Aqueous Methanol Solution

“…The 4-(dialkylamino)pyridine-functionalized polymers have been widely regarded as useful model systems for attaining goals of mimicking enzymic efficiency and selectivity. − Macromolecule 1 containing the 4-(dialkylamino)pyridine functionality and a bis(trimethylene)disiloxane group in its backbone structure exhibits enzyme-like substrate specificity in the solvolysis of 2 ( n = 2−18) . Recently, we have found that specific salting-in effects of tris(hydroxymethyl)methylammonium ion lead to 1 -catalyzed hydrolysis reaction of 2 ( n = 2−16) with clear preference for 2 ( n = 6) in aqueous solution, , which is the same substrate specificity obtained with cholesterol esterase , in the hydrolysis of p -nitrophenyl esters 2 . The salting-out effects of sodium chloride were found to reduce significantly the substrate preference for 1 -catalyzed solvolysis of 2 ( n = 10−16) at higher NaCl concentrations .…”