Investigation on the micro-mechanisms of Al3+ interfering the reactivities of aspartic acid and its biological processes with Mg2+

Density functional theory (DFT) has been applied to study the micro-mechanisms of Al³⁺ interfering the reactivities of aspartic acid (H₂asp) and its biological processes with Mg²⁺. All the 46 stable conformers of Hasp^- and 3 of asp²⁻ have been determined at the B3LYP/6-311++G** level, showing that the 7 most stable conformers of Hasp⁻ all present a very strong and linear O–H···O H-bond between carboxyl and carboxylic acid groups with the bond energy high up to 162 kJ mol⁻¹. The reaction thermodynamics and micro-mechanism between Al³⁺ and Hasp⁻ (or asp²⁻) in aqueous phase have been investigated by the combined application of supramolecular model and polarizable continuum IEFPCM solvent model, firstly revealing Al³⁺ interfering in the biological processes of aspartic acid. The substitution thermodynamics and mechanisms of Mg²⁺ by Al³⁺ in the biological processes between the species of aspartic acid and Mg²⁺ in aqueous phase were probed, revealing the facile displacement of Mg²⁺ by Al³⁺. These results may provide a reasonable mechanism of Al³⁺ biological toxicity at the microscopic level.