Theoretical investigations on the chiral transition of Cu(ii) chelated by bis--alanine in the aqueous-liquid phase

The chiral enantiomeric transition of bis-alpha-alanine chelated Cu(ii) complexes (alpha-Ala)(2)-Cu(ii) was investigated for the first time using the M06 and MN15 methods of density functional theory combined with the SMD model approach of self-consistent reaction field theory. It is found that the chiral transformation of (S-alpha-Ala)(2)-Cu(ii) goes through two processes. The first process is the hetero-formation of R-alpha-Ala by a single S-alpha-Ala enantiomer isomerization in (S-alpha-Ala)(2)-Cu(ii), R-allo-alpha-Ala-Cu(ii) is obtained; The second process is the enantiomer transition of S-alpha-Ala to R-alpha-Ala in R-allo-alpha-Ala-Cu(ii), resulting in (R-alpha-Ala)(2)-Cu(ii). Complete chiral transformation is achieved. It is found that there are three pathways in the first process, which are named pathway a, pathway b and pathway c. Among them, the chiral transformation process of pathway c has comparative advantages, the rate-determining step energy barrier for the enantiomeric transition of (S-alpha-Ala)(2)-Cu(ii) into R-allo-alpha-Ala-Cu(ii) in the implicit aqueous solvent model is 54.3 kcal mol(-1), the energy barrier is reduced to 26.3 kcal mol(-1) by the action of water molecular clusters. In the second process, it is found that the chiral transformation of each of the pathways are similar to the first process. Therefore, the pathway reaction mechanism with the relative advantage of chiral transition is studied. The rate-determining step energy barrier of R-allo-alpha-Ala-Cu(ii) enantiomer transition to (R-alpha-Ala)(2)-Cu(ii) is 49.9 kcal mol(-1) in the implicit aqueous solvent model, the effect of water molecular clusters reduces the energy barrier to 27.1 kcal mol(-1). The chelated Cu(ii) with double alpha-Ala in aqueous solution can maintain its chirality well and is relatively safe for supplementing copper and alpha-Ala in living organisms.