Theoretical Calculations of the Multistep Reaction Mechanism Involved in Asparagine Pyrolysis Supported by Degree of Rate Control and Thermodynamic Control Analyses

Abstract

A computational study on the mechanisms of reaction for the pyrolysis of asparagine is presented. A density functional theory (DFT) study at the ωB97XD/6-311G(d,p) level was performed to analyze the differences in two reaction mechanisms: (i) the formation of five-membered cyclic products: maleimide and succinimide, and (ii) the more classical, six-membered cyclic products (diketopiperazine species) which are common in the pyrolysis of many other amino acids. The effect of temperature was included in the calculations at 300 °C or 625 °C, as required. Moreover, a detailed study based on the degree of rate control and thermodynamic control of the proposed mechanism for the formation of maleimide and succinimide is also presented. Results show that, for asparagine, the five-membered ring formation is the preferred process instead of the six-membered cycle (32 kJ/mol of Gibbs free energy difference between them at the first cyclization step); therefore, the polymerization is favored. On the other hand, the rupture of the polymer represents the highest energetic barrier (ΔG‡ = 281 kJ/mol) and the most influential process in the overall rate of the reaction. These results are in good agreement with the experimental evidence.

Theoretical and Experimental Insights into the Tandem Mannich—Electrophilic Amination Reaction: Synthesis of Safirinium Dyes

“…2021, 11, x FOR PEER REVIEW 2 of 13 ens of hours [4]. The aim of the present study was to describe the tandem Mannich-electrophilic amination reactions using commonly recognized theoretical quantum chemical methods [8][9][10] and identify the steric factors that would limit applications of these processes in a fast and sensitive detection of formaldehyde and fluorescent derivatization of secondary aliphatic amines.…”

“…The tandem reactions of non-fluorescent isoxazolones, formaldehyde and secondary amines, i.e., syntheses of Safirinium dyes, proceed quantitatively, however the reaction rates strongly depend on the substitution pattern, which results in reaction times ranging from several minutes to dozens of hours [4]. The aim of the present study was to describe the tandem Mannichelectrophilic amination reactions using commonly recognized theoretical quantum chemical methods [8][9][10] and identify the steric factors that would limit applications of these pro-Appl. Sci.…”

In Silico Screening of the DrugBank Database to Search for Possible Drugs against SARS-CoV-2

“…The main purpose of this section was to investigate whether or not the frontier orbitals shapes could allow qualitatively distinguishing structures with high vs. low anti-COVID-19 activity. For this purpose, the selected structures were optimized at the DFT theory level with the WB97XD/6-311G(d,p) [ 82 , 93 , 111 , 112 ] method, implemented in Gaussian 16 [ 113 ] for Linux. Following optimization, the .chks files were retrieved and used to generate the frontier molecular orbitals with a 0.02 au isosurface.…”

Cyclic Compound Formation Mechanisms during Pyrolysis of Typical Aliphatic Acidic Amino Acids

“…36−39 Therefore, ωB97XD was employed to obtain a more accurate result. 33 The energy barrier of the reaction (free-energy barrier, ΔG*) was estimated using relative energy, including zero-point energy correction (ZPE) between the transition state and the reactants. Standard thermodynamic changes were obtained from the difference between the thermodynamic values of the reactants and products.…”

“…32 Cervantes et al performed a DFT calculation on the asparagine pyrolysis mechanism at the ωB97XD/6-311G (d, p) level to study the five-ring and sixring product formation. 33 Using DFT methods to study amino acid pyrolysis product formation needs more attention as the detailed N-PAC formation mechanism is still unclear. As we all know, quantum chemical calculations play an essential role in the study of chemical reaction mechanisms.…”