Theoretical study for determining the type of interactions between a GG block of an alginate chain with metals Cu²⁺, Mn²⁺, Ca²⁺ and Mg²⁺

The alginate interaction with divalent cations has been the subject of extensive study since this biopolymer forms hydrogels in the presence of divalent cations (ionic crosslinking), which exhibit important properties with applications in fields such as medicine. It has been proposed that the properties of the hydrogel formed from the ionic crosslinking process depend, among several factors, on the type of interactions between the polymer and divalent metals. In this work, theoretical calculations based on density functional theory (DFT) were used to determine the chemical stability and the type of interaction between alginate and Cu²⁺, Mn²⁺, Ca²⁺ and Mg²⁺ cations. For this, the lowest energy geometries were determined at the B3LYP 6-31G (d, p) level of theory for the systems formed with Ca²⁺ and Mg²⁺, while those formed with Cu²⁺ and Mn²⁺ used effective central potential (ECP) with LanL2DZ bases. The following models were used to characterize the bonds between the oxygen atoms of the polymer chain with the different metals; theory of non-covalent interactions (NCI), natural bonding orbitals (NBO) method, and topological analysis of the electronic location function (ELF). Our results showed that the properties such as chemical stability of the systems would be correlated with the degree of covalence of the bonds and the delocalization phenomena charge, where the systems constituted with Cu²⁺ and Mn²⁺ formed bonds with highly polarized covalent characteristics, while Ca²⁺ and Mg²⁺ form bonds of the electrostatic type. Nevertheless, our results support the idea proposed by previous studies; regarding the lack of correlation between the alginate for divalent cations affinity with the strength of the interactions between these metals and the polymer.