Theoretical Study On The Catalytic Mechanism Of Amino Acids And The Confinement Effects Of Hydrotalcite

As the basic unit of peptides and protein, the structures and properties of amino acids were very significantin understanding of their various biological effects and vital activities. In this paper, the isomerization mechanism of L-aspartic acid (L-ASP) and L-proline (L-PRO) and the inhibition of hydrotalcite were studied by quantum chemical method, and the mechanism and stereoselectivity of the L-ASP and its dipeptide S-PRO-S-ASP catalyzed asymmetric aldol reaction were also studied. The main results were as following:The structure and racemization mechanism of L-ASP and L-PRO and theirs intercalated magnesium-aluminum/zinc-aluminum hydrotalcite were theoretically studied by using B3LYP and PW91 method of density functional theory (DFT) at the level of 6-31G(d,p)/6-311++G(d,p)/Lanl2dz. The obtained structural parameters of intercalated materials were in agreement with the experimental data of materials indicating that the theoretical method was fit to the system of hydrotalcite. The computational results showed that the enantiomerism of L-ASP and L-PRO was difficult to take place in ground state due to the high energy barriers; and in the excited state L-ASP and L-PRO were easy to transform to D-amino acids via the proton transferring from the chiral carbon atom to the carbonyl oxygen atom, here, the carbonyl oxygen atom played a medium role of proton migration. In addition, hydrotalcite could inhibit the racemization of L-ASP and L-PRO because the combination of the oxygen atom and hydrotalcite layer hindered the movement of proton.The mechanism of the L-ASP catalyzed intermolecular aldol reaction with acetone as the donor and three aromatic aldehydes (benzaldehyde, p-methyl benzaldehyde and p-nitrobenzaldehyde) as the acceptors was studied by means of density functional theory (DFT) at the level of B3LYP/6-31G(d,p). The calculated results showed that there were four steps in the reaction path:i. the nucleophilic attack of amino group on carbonyl for the formation of alcohol-type intermediate, which was the rate-determining step due to the largest energy barrier of 173.71 kJ/mol; ii. the dehydration process to form cis-or trans-enamine through imine-generating step; iii. the electrophilic addition of aldehyde, which decided the stereoselectivity of product because of the steric repulsion interactions between enamine and aldehyde; iv. the removal of L-ASP to the final products. According to the results analysis, it was found that the L-ASP-catalyzed aldol reaction via trans-enamine was more energy favorable to obtain R-product (with an ee value> 99%). The energy variations in the reaction path were verified by using CAM-B3LYP and M06-2X methods in the same basis set. The solvation effects were explored based on B3LYP/6-31G(d,p) combined with a polarizable continuum model (PCM), the substituent effects of aromatic aldehydes were also considered. The computed results provided a reference for experiment that DMSO and H2O as the solvents could decrease the energy barriers in reaction path and the impact of substituent effects might be small.In addition, the mechanism of the dipeptide S-PRO-S-ASP catalyzed intermolecular aldol reaction with acetone as the donor and three aromatic aldehydes (benzaldehyde, p-methyl benzaldehyde and p-nitrobenzaldehyde) as the acceptors was studied by means of density functional theory (DFT) at the level of B3LYP/6-31G(d,p). The calculated results showed that there were four steps in the reaction path:ⅰ. the nucleophilic attack of amino group on carbonyl for the formation of alcohol-type intermediate, which was the rate-determining step due to the largest energy barrier of 185.59 kJ/mol; ⅱ. the dehydration process to form cis- or trans-enamine through imine-generating step; ⅲ. the electrophilic addition of aldehyde, which decided the stereoselectivity of product because of the steric repulsion interactions between enamine and aldehyde; ⅳ. the removal of dipeptide to the final products. According to the results analysis, it was found that the dipeptide-catalyzed aldol reaction via trans-enamine was more energy favorable to obtain R-product (with an ee value> 99%). The energy variations in the reaction path were verified by using CAM-B3LYP and M06-2X methods in the same basis set. The solvation effects were explored based on B3LYP/6-31G(d,p) combined with a polarizable continuum model (PCM), the substituent effects of aromatic aldehydes were also considered. The computed results provided a reference for experiment that DMSO and H2O as the solvents could decrease the energy barriers in reaction path and the impact of substituent effects might be small.