A Density Functional Theory (DFT) Study of the Acyl Migration Occurring during Lipase-Catalyzed Transesterifications

Abstract

Acyl migration (AM) is the main side reaction in the large-scale, regio-specific lipase catalyzed production of structural triglycerides (STs). A detailed understanding of the mechanism of AM was obtained during the process of lipase-catalyzed schemes (LCSs), which play a vital role in improving the quality and total yield of STs. However, currently, the mechanism of AM remains controversial. Herein, the two mechanisms (non-catalyzed (NCM) and lipase-catalyzed (LCM)) of AM have been analyzed in detail by the density functional theory (DFT) at the molecular level. Based on the computational results, we concluded that the energy barrier of the rate-limiting step in the LCM was 18.8 kcal/mol, which is more in agreement with the available experimental value (17.8 kcal/mol), indicating that LCM could significantly accelerate the rate of AM, because it has an energy barrier ~2 times lower than that of the NCM. Interestingly, we also found that the catalytic triad (Asp-His-Ser) of the lipase and water could effectively drop the reaction barrier, which served as the general acid or base, or shuttle of the proton.

Effect of Solvent on Acyl Migration of 2-Monoacylglycerols in Enzymatic Ethanolysis

“…Based on the Arrhenius equation, the activation energy can be calculated using the following equation Thus, based on the data in Table , activation energies in different media for the forward and reverse acyl migration reactions were calculated, and the results are presented in Table . The apparent activation energies in solventless, hexane, chloromethane, acetone, t -butanol, and ethanol were estimated to be 71.6, 79.2, 85.9, 90.0, 105.8, and 92.5 kJ/mol, respectively, which are significantly higher than those in lipase-catalyzed reactions . The forward and reverse reactions had similar activation energies.…”

Enzymatic Synthesis of Poly(glycerol sebacate): Kinetics, Chain Growth, and Branching Behavior

“…Acyl migration is frequently observed in the synthesis of glycerides via enzymatic or chemical catalysts, and its suppression is a difficult task. 68 , 69 The rate of acyl migration depends on reaction parameters such as temperature, glyceride concentration, and solvent polarity, and it decreases with a decrease in solvent log P or temperature. 42 , 70 − 75 For glycerol-based polyesters prepared using a chemical catalyst that selectively esterifies primary hydroxyls, Slavko and Taylor 19 reported an increase in the 1,2L unit fraction and maintenance of the 1,2,3D unit fraction when polyesters mainly composed of 1,3L units were subjected to conditions favorable for the acyl migration reaction in the absence of the esterification catalyst.…”

Acylglycerols of Myristic Acid as New Candidates for Effective Stigmasterol Delivery—Design, Synthesis, and the Influence on Physicochemical Properties of Liposomes

“…The authors detected the formation of 3a by TLC and 13 C NMR without the separation of the products mixture. In this work, both diacylglycerols 3 and 3a after separation were fully characterized using spectroscopic methods to confirm the acyl migration, which is a common phenomenon in the synthesis of structured acylglycerols, including enzymatic and chemical reaction and often limits the reaction yield leading to the formation of by-products [ 28 , 29 ].…”