4-nitrophenyl Benzoate Research Articles

N-terminal lid swapping contributes to the substrate specificity and activity of thermophilic lipase TrLipE.

TrLipE is a thermophilic lipase that has potential commercial applications because of its catalytic ability under extreme conditions. Consistent with most lipases, the lid of TrLipE is located over the catalytic pocket, controls the substrate channel to the active center, and regulates the substrate specificity, activity, and stability of the enzyme through conformational changes. TrLipE from Thermomicrobium roseum has potential industrial applications, which is hindered by its weak enzymatic activity. Here, 18 chimeras (TrL1-TrL18) were reconstructed by N-terminal lid swapping between TrLipE and structurally similar enzymes. The results showed that the chimeras had a similar pH range and optimum pH as wild TrLipE but a narrower temperature range of 40-80°C, and TrL17 and the other chimeras showed lower optimum temperatures of 70°C and 60°C, respectively. In addition, the half-lives of the chimeras were lower than those of TrLipE under optimum temperature conditions. Molecular dynamics simulations indicated that chimeras had high RMSD, RMSF, and B-factor values. When p-nitrophenol esters with different chains were used as substrates, compared with TrLipE, most of the chimeras had a low Km and high kcat value. The chimeras TrL2, TrL3, TrL17, and TrL18 could specifically catalyze the substrate 4-nitrophenyl benzoate, with TrL17 showing the highest kcat/Km value of 363.88 ± 15.83 L⋅min-1⋅mmol-1. Mutants were then designed by investigating the binding free energies of TrL17 and 4-nitrophenyl benzoate. The results indicated that single, double, and triple substitution variants (M89W and I206N; E33W/I206M and M89W/I206M; and M89W/I206M/L21I and M89W/I206N/L21I, respectively) presented approximately 2- to 3-fold faster catalysis of 4-nitrophenyl benzoate than the wild TrL17. Our observations will facilitate the development of the properties and industrial applications of TrLipE.

Thermal Effect in the Microwave-assisted Aminolysis of Benzoates and Amines

Background: Microwave selective heating thermal effect is obvious in unimolecular organic reactions. However, it is unclear whether it exists in bimolecular organic reactions under strictly controlled reaction temperature conditions. Objective: To determine whether microwave selective heating effect exists in the microwave-assisted bimolecular reactions. Methods: Hammett linear relationships in “one-pot” aminolyses of mixed 4-nitrophenyl substituted benzoates with benzylamine and 4-nitrophenyl benzoate with mixed substituted anilines were selected as molecular level probes to explore the thermal effect in the microwave-assisted bimolecular reactions. Results: In less polar solvent, there is an obvious “hot spots” effect. “One-pot” aminolyses of mixed 4-nitrophenyl substituted benzoates with benzylamine and 4-nitrophenyl benzoate with mixed substituted anilines were performed in less polar solvent toluene under oil-bath and microwave heating conditions. Generally, slopes of Hammett plots or effect of substituents on reaction rates decrease along with temperature increases under oil-bath heating conditions. Under microwave irradiation conditions, slopes of Hammett plots or effect of substituents on reaction rates decrease in comparison with those under oil-bath heating conditions at the same setting temperature, revealing that higher temperature regions (“hot spots”) still exist in intermolecular organic reactions. Conclusion: Microwave selective heating thermal effect still exists in bimolecular organic reactions under strictly controlled reaction temperature conditions, revealing that higher temperature regions (“hot spots”) do exist in intermolecular organic reactions.

Artificial cysteine-lipases with high activity and altered catalytic mechanism created by laboratory evolution

Engineering artificial enzymes with high activity and catalytic mechanism different from naturally occurring enzymes is a challenge in protein design. For example, many attempts have been made to obtain active hydrolases by introducing a Ser → Cys exchange at the respective catalytic triads, but this generally induced a breakdown of activity. We now report that this long-standing dogma no longer pertains, provided additional mutations are introduced by directed evolution. By employing Candida antarctica lipase B (CALB) as the model enzyme with the Ser-His-Asp catalytic triad, a highly active cysteine-lipase having a Cys-His-Asp catalytic triad and additional mutations W104V/A281Y/A282Y/V149G can be evolved, showing a 40-fold higher catalytic efficiency than wild-type CALB in the hydrolysis of 4-nitrophenyl benzoate, and tolerating bulky substrates. Crystal structures, kinetics, MD simulations and QM/MM calculations reveal dynamic features and explain all results, including the preference of a two-step mechanism involving the zwitterionic pair Cys105−/His224+ rather than a concerted process.

Reactivity of α-Amino Acids in the Reaction with Esters in Aqueous–1,4-Dioxane Media

The kinetics of the reaction of a series of α-amino acids with 4-nitrophenyl acetate, 4-nitrophenyl benzoate, and 2,4,6-trinitrophenyl benzoate in aqueous 1,4-dioxane medium has been studied. Kinetics of the reactions involving 4-nitrophenyl acetate and 2,4,6-trinitrophenyl benzoate has complied with the Bronsted dependence and revealed linear correlation between rate constant logarithm and the energy difference of the frontier orbitals of α-amino acids anions.

Kinetic Study on Aminolysis of 4-Nitrophenyl Nicotinate and Isonicotinate: Factors Influencing Reactivity and Reaction Mechanism

A kinetic study is reported on nucleophilic substitution reactions of 4-nitrophenyl nicotinate (7) and 4-nitrophenyl isonicotinate (8) with a series of cyclic secondary amines in <TEX>$H_2O$</TEX> containing 20 mol % DMSO at <TEX>$25.0^{\circ}C$</TEX>. The Br<TEX>${\o}$</TEX>nsted-type plots for the reactions of 7 and 8 are linear with <TEX>${\beta}_{nuc}=0.90$</TEX> and 0.92, respectively, indicating that the reactions proceed through a stepwise mechanism with expulsion of the leaving group occurring in the rate-determining step. Comparison of the reactivity of 7 and 8 with that of 4-nitrophenyl benzoate (2a) and 4-nitrophenyl picolinate (6) has revealed that their reactivity toward the amines increases in the order 2a < 7 < 8 < 6, although the reactions of these substrates proceed through the same mechanism. Factors that control reactivity and reaction mechanism have been discussed in detail (e.g., inductive and field effects, H-bonding interaction, solvent effect, etc.).

Enthalpy-Entropy Correlations in Reactions of Aryl Benzoates with Potassium Aryloxides in Dimethylformamide

Temperature dependences of the relative reactivity of potassium aryloxides XC6H4O−K+ toward 4-nitrophenyl (1), 3-nitrophenyl (2), 4-chlorophenyl (3), and phenyl (4) benzoates in dimethylformamide (DMF) were studied using the competitive reactions technique. The rate constants kX for the reactions of 1 with potassium 4-cyanophenoxide, 2 with potassium 3-bromophenoxide, 3 with potassium 3-bromo-, 4-bromo-, and unsubstituted phenoxides, 4 with potassium 4-methoxy- and 3-methylphenoxides were measured at 25°C. Correlation analysis of the relative rate constants kX/kH(3-Me) and differences in the activation parameters (∆∆Н≠ and ∆∆S≠) of competitive reactions revealed the existence of six isokinetic series. We investigated the substituent effect of X on the activation parameters for each isokinetic series and concluded that the reactions of aryl benzoates PhCO2C6H4Y with potassium aryloxides in DMF proceed via a four-step mechanism. The large ρ0(Y) and ρXY values at 25°C obtained for the reactions of 1–3 with potassium aryloxides with an electron-donating substituent refer to the rate-determining formation of the spiro-σ-complex. The Hammett plots for the reactions of 1 and 2 exhibit a downward curvature, causing the motion of the transition state for the rate-determining step according to a Hammond effect as the substituent in aryloxide changes from electron-donating to electron-withdrawing. Analysis of data in the terms of two-dimensional reaction coordinate diagrams leads to the conclusion that significant anti-Hammond effects arise in the cases of ortho-substituted and unsubstituted substrates. It was shown that the isokinetic and compensation effects observed for the reactions of aryl benzoates with potassium aryloxides in DMF can be interpreted in the terms of the electrostatic bonding between the reaction centers.

A Kinetic Study on Nucleophilic Substitution Reactions of Phenyl Y-Substituted-Phenyl Carbonates with Z-Substituted-Phenoxides: Effect of Modification of Nonleaving Group from Benzoyl to Phenyloxycarbonyl on Reactivity and Reaction Mechanism

Second-order rate constants for the reactions of phenyl Y-substituted-phenyl carbonates 5a-g with Z-substituted-phenoxides (<TEX>$k_{Z-PhO^-}$</TEX>) have been measured spectrophotometrically in 80 mol % <TEX>$H_2O$</TEX>/20 mol % DMSO at <TEX>$25.0{\pm}0.1^{\circ}C$</TEX>. 4-Nitrophenyl phenyl carbonate (5e) is up to 235 times more reactive than 4-nitrophenyl benzoate (4e). The Br<TEX>$\o$</TEX>nsted-type plot for the reactions of 5e with Z-substituted-phenoxides is linear with <TEX>${\beta}_{nuc}=0.54$</TEX>, which is typical for reactions reported previously to proceed through a concerted mechanism. Hammett plots correlated with <TEX>${\sigma}^o$</TEX> and <TEX>${\sigma}^-$</TEX> constants for the reactions of 5a-f with 4-chlorophenoxide exhibit highly scattered points. In contrast, the Yukawa-Tsuno plot results in an excellent linear correlation with <TEX>${\rho}_Y=1.51$</TEX> and r = 0.52, indicating that the leaving-group departure occurs at the rate-determining step (RDS). A stepwise mechanism, in which leaving-group departure occurs at RDS, has been excluded since the incoming 4-<TEX>$ClPhO^-$</TEX> is more basic and a poorer nucleofuge than the leaving Y-substituted-phenoxides. Thus, the reaction has been concluded to proceed through a concerted mechanism. Our study has shown that the modification of the nonleaving group from benzoyl to phenyloxycarbonyl causes a change in the reaction mechanism (i.e., from a stepwise mechanism to a concerted pathway) as well as an increase in the reactivity.

Activation parameters of transesterification of 4-nitrophenyl acetate in the presence of K2CO3 in DMF

The activation parameters for the reactions of 4-nitrophenyl acetate with 4-chlorophenol and benzenethiol in the presence of potassium carbonate in dimethylformamide were determined. Depending on the substrate structure, the enthalpy and entropy of activation decrease in going from 4-nitrophenyl acetate to 4-nitrophenyl benzoate, while the Gibbs energy of activation increases.

Ammonia reactivity in the acylation with 4-nitrophenyl benzoate in a water-2-propanol system

The kinetics of acylation of ammonia with 4-nitrophenylbenzoates in water-2-propanol mixtures was studied. Increase in the reaction rate with increasing proportion of water in the system is attributed to the formation of ammonia solvato complexes with the components of the solvent. By the RHF/6-31G* method were calculated structural and energetic properties of the solvato complexes. The potential energy surfaces of the acylation reaction of ammonia and its solvato complexes were calculated. It was shown that solvation of the transition state decreases the reaction activation energy compared to the gas-phase process. All the reactions proceed by SN2 mechanism without formation of intermediates, with only one transition state.

Metal Ion Catalysis and Inhibition in Nucleophilic Substitution Reactions of 4-Nitrophenyl Nicotinate and Isonicotinate with Alkali Metal Ethoxides in Anhydrous Ethanol

A kinetic study is reported on nucleophilic substitution reactions of 4-nitrophenyl nicotinate 5 and isonicotinate 6 with alkali metal ethoxide EtOM (M = K, Na, and Li) in anhydrous ethanol at <TEX>$25.0{\pm}0.1^{\circ}C$</TEX>. Plots of pseudo-first-order rate constant <TEX>$k_{obsd}$</TEX> vs. EtOM concentration exhibit upward curvature for the reactions of 5 and 6 with EtOK and EtONa but are almost linear for those with EtOLi. Dissection of <TEX>$k_{obsd}$</TEX> into <TEX>$k_{EtO^-}$</TEX> and <TEX>$k_{EtOM}$</TEX> (i.e., the second-order rate constant for the reaction with dissociated <TEX>$EtO^-$</TEX> and ion-paired EtOM, respectively) has shown that <TEX>$k_{EtOK}$</TEX> <TEX>${\geq}$</TEX> <TEX>$k_{EtONa}$</TEX> > <TEX>$k_{EtO^-}$</TEX> but <TEX>$k_{EtOLi}$</TEX> < <TEX>$k_{EtO^-}$</TEX>. It has been concluded that <TEX>$K^+$</TEX> and <TEX>$Na^+$</TEX> ions catalyze the reactions by increasing the electrophilicity of the carbonyl carbon atom through formation of a 4-membered cyclic transition state <TEX>$TS_3$</TEX> or <TEX>$TS_4$</TEX>. However, <TEX>$M^+$</TEX> ion catalysis has been found to be much less significant for the reactions of 5 and 6 than for the corresponding reactions of 4-nitrophenyl picolinate 4, which was reported to proceed through a 5-membered cyclic transition state <TEX>$TS_2$</TEX>. Although 5 and 6 are significantly more reactive than 4-nitrophenyl benzoate 3, the reactions of 5 and 6 result in smaller <TEX>$k_{EtOK}/k_{EtO^-}$</TEX> ratios than those of 3. The electron-withdrawing ability of the nitrogen atom in the acyl moiety of 5 and 6 has been suggested to be responsible for the increase in reactivity and the decrease in the <TEX>$k_{EtOK}/k_{EtO^-}$</TEX> ratio.

Aminolysis of S-4-Nitrophenyl X-Substituted Thiobenzoates: Effect of Nonleaving-Group Substituents on Reactivity and Mechanism

C. Thiol esters 3a-g are 7.8-47.6 fold more reactive than the correspondingoxygen esters (i.e., 4-nitrophenyl X-substituted benzoates 1a-g). Such reactivity order appears to be inaccordance with the expectation that 4-nitrothiophenoxide in 3a-g is a better nucleofuge than 4-nitrophenoxidein 1a-g since the former is 2.64 p K

A Kinetic Study on Aminolysis of 2-Pyridyl X-Substituted Benzoates: Effect of Changing Leaving Group from 4-Nitrophenolate to 2-Pyridinolate on Reactivity and Mechanism

Second-order rate constants (<TEX>$k_N$</TEX>) have been measured spectrophotometrically for nucleophilic substitution reactions of 2-pyridyl X-substituted benzoates 8a-e with a series of alicyclic secondary amines in <TEX>$H_2O$</TEX> at <TEX>$25.0{\pm}0.1^{\circ}C$</TEX>. The <TEX>$k_N$</TEX> values for the reactions of 8a-e are slightly smaller than the corresponding reactions of 4-nitrophenyl X-substituted benzoates 1a-e (e.g., <TEX>$kN^{1a-e}/k_N^{8a-e}$</TEX> = 1.1 ~ 3.1), although 2-pyridinolate in 8a-e is ca. 4.5 <TEX>$pK_a$</TEX> units more basic than 4-nitrophenolate in 1a-e. The Br<TEX>$\o$</TEX>nsted-type plot for the aminolysis of 8c (X = H) is linear with <TEX>$\beta_{nuc}$</TEX> = 0.77 and <TEX>$R^2$</TEX> = 0.991 (Figure 1), which is typical for reactions reported previously to proceed through a stepwise mechanism with breakdown of a zwitterionic tetrahedral intermediate <TEX>$T^{\pm}$</TEX> being the rate-determining step (RDS), e.g., aminolysis of 4-nitrophenyl benzoate 1c. The Hammett plot for the reactions of 8a-e with piperidine consists of two intersecting straight lines (Figure 2), i.e., <TEX>$\rho$</TEX> = 1.71 for substrates possessing an electron-donating group (EDG) while <TEX>$\rho$</TEX> = 0.86 for those bearing an electron-withdrawing group (EWG). Traditionally, such a nonlinear Hammett plot has been interpreted as a change in RDS upon changing substituent X in the benzoyl moiety. However, it has been proposed that the nonlinear Hammett is not due to a change in RDS since the corresponding Yukawa-Tsuno plot exhibits excellent linear correlation with <TEX>$\rho$</TEX> = 0.85 and r = 0.62 (<TEX>$R^2$</TEX> = 0.995, Figure 3). Stabilization of substrates 8a-e in the ground state has been concluded to be responsible for the nonlinear Hammett plot.

Catalytic nanoreactors for ester hydrolysis

Hydrolysis of 4-nitrophenyl benzoate (PNPB) in the presence of ionene nanoreactors was studied comparing the ionenes, poly[(dimethyl)-2-hydroxy propanodiyl chloride] (2-OH-33R1), poly[(methylbutyliminium)-2-hydroxy propanodiyl chloride] (2-OH-33R4) and poly[(methyloctyliminium)-2-hydroxy propanodiyl chloride] (2-OH-33R8). Methyl orange incorporation and study of viscosity showed that increase of the side chain length of the ionene enhances the ability to form globular hydrophobic microdomains. Catalytic hydrolysis of PNPB follows the order 2-OH-33R8 ≫ 2-OH-33R4 > 2-OH-33R1, and 2-OH-33R8 has the lowest p K a that may reflect its higher hydrophobicity, which apparently influences the ionene nanoreactor reactivity. A lower p K a indicates easier deprotonation of the alkoxide group, which participates more effectively in the reaction and the 2-OH-33R8 functionalized ionene acts as a specially effective catalytic homogeneous nanoreactor.

Effect of nucleophile on the activation parameters of transesterification of 4-nitrophenyl benzoates

Activation parameters of the reaction of 4-nitrophenyl benzoates with benzenethiol in the presence of potassium carbonate in dimethylformamide were determined. The entropies of activation for the reactions of unsubstituted 4-nitrophenyl benzoate and 4-nitrophenyl benzoates having donor substituents are positive. The relative contributions of the enthalpy and entropy of activation to the Gibbs energy of activation are discussed. Variation of the activation parameters upon replacement of benzenethiol by 4-chlorophenol is analyzed.

Effect of Alkali Metal Ions on Nucleophilic Substitution Reactions of 4-Nitrophenyl X-Substituted Benzoates with Alkali Metal Ethoxides in Anhydrous Ethanol

Pseudo-first-order rate constants (<TEX>$k_{obsd}$</TEX>) have been measured spectrophotometrically for nucleophilic substitution reactions of 4-nitrophenyl benzoate (5a), 4-nitrophenyl 4-methoxybenzoate (5b), and 4-nitrophenyl 4-hydroxybenzoate (5c) with alkali metal ethoxides, <TEX>$EtO^-M^+$</TEX> (<TEX>$M^+=Li^+$</TEX>, <TEX>$Na^+$</TEX> and <TEX>$K^+$</TEX>) in anhydrous ethanol (EtOH) at <TEX>$25.0{\pm}0.1^{\circ}C$</TEX>. The plots of <TEX>$k_{obsd}$</TEX> vs. [<TEX>$EtO^-M^+$</TEX>] exhibit upward curvatures in all cases, indicating that <TEX>$M^+$</TEX> ions catalyze the reactions and ionpaired <TEX>$EtO^-M^+$</TEX> species are more reactive than dissociated <TEX>$EtO^-$</TEX>. Second-order rate constants for reactions with dissociated <TEX>$EtO^-$</TEX> and ion-paired <TEX>$EtO^-M^+$</TEX> (i.e., <TEX>$k_{EtO^-}$</TEX> and <TEX>$k_{EtO^-M^+}$</TEX>, respectively) have been calculated from ion-pair treatment for the reactions of 5a and 5b. However, such ion-pair treatment has failed to determine <TEX>$k_{EtO^-}$</TEX> and <TEX>$k_{EtO^-M^+}$</TEX> values for the reactions of 5c. It has been concluded that reactions of 5a and 5b are catalyzed by one metal ion, which increases electrophilicity of the reaction center through coordination on the carbonyl oxygen. In contrast, reactions of 5c have been suggested to involve two metal ions, i.e., the one coordinated on the carbonyl oxygen increases the electrophilicity of the reaction center while the other one associated on the phenoxy oxygen decreases the charge repulsion between the anionic reagents (i.e., <TEX>$EtO^-$</TEX> and deprotonated 5c). It has been found that the rate equation derived from the mechanism involving two metal ions fits nicely to the kinetic results obtained for the reactions of 5c.

Kinetics and Mechanism of Nucleophilic Displacement Reactions of Y-Substituted Phenyl Benzoates with Z-Substituted Phenoxides

Second-order rate constants have been measured for two series of nucleophilic displacement reactions, i.e., reactions of 4-nitrophenyl benzoate with Z-substituted phenoxides and those of Y-substituted phenyl benzoates (1a-h) with 4-chlorophenoxide (4-ClPhO–) in 80 mol% <TEX>$H_2O$</TEX>/20 mol% DMSO at 25.0 <TEX>${\pm}\;0.1\;{^{\circ}C}$</TEX>. The Br<TEX>$\phi$</TEX>nsted-type plot for reactions of 4-nitrophenyl benzoate with Z-substituted phenoxides exhibits an excellent linear correlation with <TEX>${\beta}_{nuc}$</TEX> = 0.72. Reactions of 1a-h with 4-chlorophenoxide result in also a linear Br<TEX>$\phi$</TEX>nsted-type plot with <TEX>${\beta}_{lg}$</TEX> = –0.62, a typical <TEX>${\beta}_{lg}$</TEX> value for a concerted mechanism. The Hammett plots correlated with <TEX>${\sigma}^o\;and\;{\sigma}^-$</TEX> constants show many scattered points for reactions of 1a-h with 4-chlorophenoxide. In contrast, the corresponding Yukawa-Tsuno plot exhibits an excellent linear correlation with <TEX>$\rho_Y$</TEX> = 2.26 and r = 0.53, indicating that expulsion of the leaving group occurs at the rate-determining step (RDS) either in a concerted mechanism or in a stepwise pathway. However, a stepwise mechanism with leaving group departure being the RDS is excluded since the leaving Y-substituted phenoxide is less basic and a better nucleofuge than the incoming 4-ClPh<TEX>$O^-$</TEX>. Thus, the reactions have been concluded to proceed through a concerted mechanism, in which bond formation between the nucleophile and electrophilic center is more advanced than expulsion of the leaving group in the transition state on the basis of the magnitude of <TEX>${\beta}_{nuc}\;and\;{\beta}_{lg}$</TEX> values.

Quantum chemical interpretation of reactivities of aliphatic amines and α-amino acids in acylation

Quantum chemical calculations of geometrical, electronic, and energy characteristics for aliphatic amines, ammonia, some α-amino acids, and 4-nitrophenyl benzoate (4-NPB) have been performed. By the QSPR method, it was found that the rate constants for the reactions of amino compounds specified with 4-NPB in water—propan-2-ol solvent mixture are linearly dependent on the contribution of the 2pz-AO of nitrogen into the HOMO, as well as on the population of the 2pz-AO of nitrogen. Different character of the dependencies for 6h-amino acids and aliphatic amines can be explained by their involvement into formation of solvato-complexes with different reactivity.

Activation parameters of the reactions of 4-nitrophenyl benzoates and S-phenyl benzothioate with 4-chlorophenol in dimethylformamide in the presence of potassium carbonate

The kinetics of transesterification of 4-nitrophenyl benzoates and S-phenyl benzothioate with 4-chlorophenol in dimethylformamide in the presence of potassium carbonate were studied. Variation of the substrate reactivity and activation parameters of the process is discussed with respect to the substituent in the benzoic acid fragment.

Reaction Mechanism and Structure of Transition State Determined from Analysis of Bronsted βnucfor Aminolysis of 4-Nitrophenyl Diphenylphosphinate

Useful information on reaction mechanism can be obtained from analysis of Bronsted-type plots. Curved Bronstedtype plots often found for reactions of esters possessing a good leaving group (e.g., 2,4-dinitrophenoxide) have been taken as evidence for a change in the rate-determining step (RDS) of a stepwise mechanism. In fact, a curved Bronsted-type plot has been reported for reactions of 2,4dinitrophenyl benzoate (1) with a series of alicyclic secondary amines, i.e., the βnuc value decreases from 0.74 to 0.34 as the amine basicity increases. In contrast, the corresponding reactions of 4-nitrophenyl benzoate (2) resulted in a linear Bronsted-type plot with βnuc = 0.88 in the pKa range 5.9511.02. Thus, it has been concluded that the aminolyses of 1 and 2 proceed through a stepwise mechanism and the RDS changes in the reactions of 1 but not in the reactions of 2 in that pKa range. 4a,b

Kinetics of the reaction of substituted 4-nitrophenyl benzoates with benzenethiol in the presence of potassium carbonate in dimethylformamide

The effect of the substituent nature on the rate and activation parameters of transesterification of a series of 4-nitrophenyl benzoates with benzenethiol in dimethylformamide in the presence of potassium carbonate was studied by the competing reaction method. In all cases, change of the Gibbs energy of activation is determined mainly by variation of the enthalpy of activation. 4-Nitrophenyl benzoates having electron-withdrawing substituents in the benzoyl fragment were found to fit an isokinetic relation with an isokinetic temperature β of 318 K. Enthalpy-entropy compensation effect was observed in the reactions with all the examined 4-nitrophenyl benzoates. The relation between the reactivity and polarizability of nucleophilic center in S-and O-nucleophiles is discussed.