Anionic species from multivalent metal salts are differentially retained during aqueous ionic gelation of sodium alginate and could fine-tune the hydrogel properties.

The role of anionic counterions of divalent metal salts in alginate gelation and hydrogel properties has been thoroughly investigated. Three anions were selected from the Hofmeister series, namely sulphate, acetate and chloride, paired in all permutations and combinations with divalent metal cations like calcium, zinc and copper. Spectroscopic analysis revealed the presence of anions and their interaction with the respective metal cations in the hydrogel. The data showed that the gelation time and other hydrogel properties were largely controlled by cations. However, subtle yet significant variations in viscoelasticity, water uptake, drug release and cytocompatibility properties were anion dependent in each cationic group. Computational modelling based study showed that metal-anion-alginate configurations were energetically more stable than the metal-alginate models. The in vitro and in silico studies concluded that acetate anions preceded chlorides in the drug release, swelling and cytocompatibility fronts, followed by sulphate anions in each cationic group. Overall, the data confirmed that anions are an integral part of the metal-alginate complex. Furthermore, anions offer a novel option to further fine-tune the properties of alginate hydrogels for myriads of applications. In addition, full exploration of this novel avenue would enhance the usability of alginate polymers in the pharmaceutical, environmental, biomedical and food industries.