The substituent effects of the leaving groups on the aminolysis of phenyl acetates: DFT studies

Yi, Guang-Quan; Zeng, Yi; Xia, Xuefei; Yang, Xue; Kim, Chan-Kyung; Gao, Yan

doi:10.1016/j.chemphys.2008.01.036

Cited by 18 publications

(5 citation statements)

References 35 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To our knowledge, few efforts have been made to investigate systemically the substituent effects on the ester aminolysis by applying a higher level of electron structure theory and solvent effects determined by Monte Carlo simulation from a theoretical point of view. We employed the density functional theory B3LYP/6−31G(d, p) method to study the substituent effects of the leaving groups on aminolysis of p-substituted phenyl acetates with ammonia . In the present work, we aim to examine the effects of the nonleaving group substituents and solvents on the aminolysis of methylformates XC(O)OCH 3 (X = H, NH 2 , and CF 3 ).…”

Section: Introductionmentioning

confidence: 99%

“…We employed the density functional theory B3LYP/6-31G(d, p) method to study the substituent effects of the leaving groups on aminolysis of p-substituted phenyl acetates with ammonia. 41 In the present work, we aim to examine the effects of the nonleaving group substituents and solvents on the aminolysis of methylformates XC(O)OCH 3 (X ) H, NH 2 , and CF 3 ). In each case of the concerted and stepwise pathways, two processes, the direct aminolysis (with monomeric ammonia molecule) and the ammonia-assisted aminolysis (with dimeric ammonia), are considered (see Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

DFT Study and Monte Carlo Simulation on the Aminolysis of XC(O)OCH₃ (X = NH₂, H, and CF₃) with Monomeric and Dimeric Ammonias

Xia

Zhang

Yang

et al. 2008

J. Chem. Theory Comput.

Self Cite

View full text Add to dashboard Cite

The aminolysis of substituted methylformates (XC(O)OCH3, X = NH2, H, and CF3) in the gas phase and acetonitrile are investigated by the density functional theory B3LYP/6-311+G(d,p) method and Monte Carlo (MC) simulation with free energy perturbation (FEP) techniques. The direct and the ammonia-assisted aminolysis processes are considered, involving the monomeric and dimeric ammonia molecules, respectively. In each case, two different pathways, the concerted and stepwise, are explored. The calculated results show that, for the direct aminolysis, the activation barrier of the concerted path is lower than that of the rate-controlling step of the stepwise process for all three reaction systems. In contrast, for the ammonia-assisted mechanism, the stepwise process is more favorable than the concerted pathway. The substituent effects at the carboxyl C atom of methylformate are discussed. This aminolysis of substituted methylformates is more favored for X = CF3 than for X = H and NH2 in the gas phase for both the direct and the ammonia-assisted processes. Solvent effects of CH3CN on the reaction of HC(O)OCH3 + nNH3 (n = 1, 2) are determined by Monte Carlo simulation. The potential energy profiles along the minimum energy paths in the gas phase and in acetonitrile are obtained. It is shown that CH3CN lowers the energy barriers of all reactions.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DFT Study and Monte Carlo Simulation on the Aminolysis of XC(O)OCH₃ (X = NH₂, H, and CF₃) with Monomeric and Dimeric Ammonias

Xia

Zhang

Yang

et al. 2008

J. Chem. Theory Comput.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Some works reported that the solvent effect little influences compound structures. 34,35 From information shown in Figure 5, normal chemical bond lengths were slightly affected, about 1 pm, but the bond lengths in the center of the transition state were effected obviously, about 30 pm. Therefore, the solvent effect must necessarily be considered in the optimization of the geometry structure, especially for transition states in reactions.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Hydrolysis Reaction Mechanism in Atrazine Metabolism and Prediction of Its Metabolites’ Toxicities

et al. 2014

J. Agric. Food Chem.

View full text Add to dashboard Cite

Atrazine (ATR) is a widely used herbicide. There are several types of reactions in its metabolism. Herein, the mechanism of three paths of hydrolysis reactions in its metabolism and predictions of toxicities of its metabolites in the three paths will be presented. The calculation results by B3LYP (Becke, 3-parameter, Lee-Yang-Parr), one of the approaches in density functional theory, indicated that (1) there were three models in the three hydrolysis paths of ATR. The dissociation mechanisms of C(9/11)-N(8/10), C(4/6)-N(8/10), and C-Cl were dealkylation, deamination, and Cl substitution, respectively. (2) The energy barrier of C-Cl dissociation was lower. The dissociation was advantageous in dynamics and the primary reaction in the three hydrolysis paths. In these hydrolysis reactions, the different intermediates had different concentrations because of the impact of the reaction rate. (3) In addition, it was necessary to consider the solvent effect to investigate hydrolysis reaction. The conductor-like polarizable continuum model (CPCM) was used to simulate the hydrolysis reaction in bond length and energy barrier because of the solvent effect. Experimental or predictive results showed that atrazine and its metabolites in the three hydrolysis paths were carcinogenic.

show abstract

“…The trend within the fluorinated phenyl esters is for increasing fluorination to favor reaction thermodynamics, with the tetrafluoro-and pentafluorophenyl esters having comparable free energies of reactions with methylamine to those of the p-nitrophenyl leaving group. Reactions of phenyl [96][97][98][99][100], p-nitrophenyl [84,93,98,101], and fluorophenyl esters [92,93] have been studied experimentally and computationally with various nucleophiles and solvents, with a focus on the transition state structures. For example, a theoretical study of the aminolysis of para-substituted phenyl acetates in vacuo and in acetonitrile was undertaken at the B3LYP/6-31+G(d,p) level of theory, and for the reaction of phenyl acetate with ammonia, a reaction energy (∆E) of −13.09 kcal/mol (−54.77 kJ/mol) was computed.…”

Section: Phenyl and N-hydroxysuccinimide Estersmentioning

confidence: 99%

Thermodynamic Overview of Bioconjugation Reactions Pertinent to Lysine and Cysteine Peptide and Protein Residues

Lopandic,

Merza,

Honek

2023

Compounds

View full text Add to dashboard Cite

Bioconjugation reactions are critical to the modification of peptides and proteins, permitting the introduction of biophysical probes onto proteins as well as drugs for use in antibody-targeted medicines. A diverse set of chemical reagents can be employed in these circumstances to covalently label protein side chains, such as the amine moiety in the side chain of lysine and the thiol functionality in cysteine residues, two of the more frequently employed sites for modification. To provide researchers with a thermodynamic survey of the reaction of these residues with frequently employed chemical modification reagents as well as reactive cellular intermediates also known to modify proteins non-enzymatically, a theoretical investigation of the overall thermodynamics of models of these reactions was undertaken at the T1 and G3(MP2) thermochemical recipe levels (gas phase), the M06-2X/6-311+G(2df,2p)/B3LYP/6-31G(d) (gas and water phase), and the M06-2X/cc-PVTZ(-f)++ density functional levels of theory (water phase). Discussions of the relationship between the reagent structure and the overall thermodynamics of amine or thiol modification are presented. Of additional interest are the observations that routine cellular intermediates such as certain thioesters, acyl phosphates, and acetyl-L-carnitine can contribute to non-enzymatic protein modifications. These reactions and representative click chemistry reactions were also investigated. The computational survey presented herein (>320 reaction computations were undertaken) should serve as a valuable resource for researchers undertaking protein bioconjugation. A concluding section addresses the ability of computation to provide predictions as to the potential for protein modification by new chemical entities, with a cautionary note on protein modification side reactions that may occur when employing synthetic substrates to measure enzyme kinetic activities.

show abstract

The substituent effects of the leaving groups on the aminolysis of phenyl acetates: DFT studies

Cited by 18 publications

References 35 publications

DFT Study and Monte Carlo Simulation on the Aminolysis of XC(O)OCH₃ (X = NH₂, H, and CF₃) with Monomeric and Dimeric Ammonias

DFT Study and Monte Carlo Simulation on the Aminolysis of XC(O)OCH₃ (X = NH₂, H, and CF₃) with Monomeric and Dimeric Ammonias

Hydrolysis Reaction Mechanism in Atrazine Metabolism and Prediction of Its Metabolites’ Toxicities

Thermodynamic Overview of Bioconjugation Reactions Pertinent to Lysine and Cysteine Peptide and Protein Residues

Contact Info

Product

Resources

About

The substituent effects of the leaving groups on the aminolysis of phenyl acetates: DFT studies

Cited by 18 publications

References 35 publications

DFT Study and Monte Carlo Simulation on the Aminolysis of XC(O)OCH3 (X = NH2, H, and CF3) with Monomeric and Dimeric Ammonias

DFT Study and Monte Carlo Simulation on the Aminolysis of XC(O)OCH3 (X = NH2, H, and CF3) with Monomeric and Dimeric Ammonias

Hydrolysis Reaction Mechanism in Atrazine Metabolism and Prediction of Its Metabolites’ Toxicities

Thermodynamic Overview of Bioconjugation Reactions Pertinent to Lysine and Cysteine Peptide and Protein Residues

Contact Info

Product

Resources

About

DFT Study and Monte Carlo Simulation on the Aminolysis of XC(O)OCH₃ (X = NH₂, H, and CF₃) with Monomeric and Dimeric Ammonias

DFT Study and Monte Carlo Simulation on the Aminolysis of XC(O)OCH₃ (X = NH₂, H, and CF₃) with Monomeric and Dimeric Ammonias