Theoretical Study On The Conformers Of Aspartic Acid And The Interaction Mechanism Between Al³⁺ And Aspartic Acid

The stable conformers of the neutral canonical aspartic acid and its anions (H2asp- and asp2-) have been extensively searched by density functional theory (DFT). The coordination modes of Al³⁺ with Hasp- and asp2– in the solvent of water have been investigated by the supermolecular and polarizable continuum solvent models. The competition processes between of Al³⁺ and Mg²⁺ interacting with aspartic acid were probed. The computational results reveal that the damages may be caused by Al³⁺ to the biological processes between Mg²⁺ and aspartic acid. The main achievements are shown as followings.1. Gaseous aspartic acid H2asp exists in neutral canonical form. All the 122 stable conformers of gaseous aspartic acid have been determined at the B3LYP/6-311++G** level. The relative stabilities and structural characteristics of the 15 most stable conformers have been discussed in detail. The results indicate that the Z arrangement ofα-carboxyl and the exo form ofβ-carboxyl of aspartic acid are in favor of molecular stability. Hydrogen bonds and their concerting effect provide further stabilities. The most strongest hydrogen bond was found betweenα- andβ-carboxyls. Hydrogen bonds are not the requisite for the stability of aspartic acid molecule. The arrangements ofα- andβ-carboxyls, intermolecular hydrogen bonds and ring tension in aspartic acid all affect the conformer stabilities. H2asp-exo-E/αD[g+a] is the most stable conformer of aspartic acid at the level of MP2/aug-cc-pvdz/6-311++G**.2. All the 46 stable conformers of Hasp- and 3 ones of asp2- have been obtained at the B3LYP/6-311++G** level. The relative stabilities and structural characteristics of the 15 most stable conformers of anion Hasp- and 3 stable conformers of asp2- were discussed. The results showed that all the 7 most stable conformers of Hasp- present a very strong and nearly linear O-H···O hydrogen bond (the length of H···O bond is only 1.35 1.49 ?). Its bond energy was computed, high up to 162 kJ/mol with the strength between an ordinary covalence bond and a conventional hydrogen bond. This kind of hydrogen bond plays a crucial role on the stabilities of Hasp- conformers. Hydrogen bond interactions between amino andα- orβ-carboxylate anions and the atomic steric hindrances both determine the stabilities of asp2- conformers. Hasp?-endo/εD[a g?] and asp2?-δD[g?g+] are the most stable conformers of Hasp- and asp2- at the level of MP2/aug-cc-pvdz//B3LYP/6-311++G**, respectively.3. The 38 stable conformers of [asp-Al(H2O)5]+ have been firstly determined at the B3LYP/6-311++G** level. The result showed that the stabilities of [asp-Al(H2O)5]+ conformers were primarily determined by newly-formed Al-Oasp bond (about 1.87¹.95 ?) and all kinds of hydrogen bonds, especially the strong and linear O···H-O hydrogen bonds formed between carboxylate anion and the surrounding H2O, exhibiting six-atomic ring structure .4. The 28 stable conformers of [Hasp-Al(H2O)5]²⁺ have been firstly determined at the B3LYP/6-311++G** level. The geometries of these conformers show that carboxylate anion and amino of Hasp- may seize protons from the surrounding H2O molecules to form carboxyl and ammonium ion, and simultaneously form hydrogen bonds with H2O molecules to obtain stable structures. No Al-OHasp bonds were found between Al³⁺ and Hasp- .5. The following four reactions were studied by the combination of supermolecular and IEFPCM solvent models.Calculation results of the Gibbs free energy changes of the reactions (1) and (2) showed that the reactions of [Al(H2O)6]³⁺ and asp2- or Hasp- can take place spontaneously in aqueous phase (ΔG=-47.43, -1.92 kJ/mol, respectively). This result firstly provided a theoretical support for Al³⁺ entry to organism and then influencing biological processes of aspartic acid.Furthermore, computational results of the Gibbs free energy changes of the reactions (3) and (4) show that the reactions of [Al(H2O)6]³⁺ and asp-Mg(H2O)5 or [Hasp-Mg(H2O)5]+ can also process spontaneously (ΔG=-53.53, 129.45 kJ/mol, respectively). This result firstly provided a theoretical support for Al³⁺ influencing the biological processes of Mg²⁺ combined with aspartic acid, revealing the possible mechanism of Al³⁺ biological toxicity at the microcosmic level.In summary, this paper focuses as on aspartic acid and the possible interaction mechanism between Al³⁺ and aspartic acid. The results shine a light on the biological toxicity of Al³⁺ at the microcosmic level.