The cation effect on the solubility of glycylglycine and N-acetylglycine in aqueous solution: Experimental and molecular dynamic studies

The specific interactions of ions with biomolecules in aqueous solutions play a very important role in the life sciences and biotechnology. This work aims to study the effect of NaCl, KCl, NH4Cl, CaCl2 or MgCl2 on the solubility of two glycine derivatives, glycylglycine (a.k.a. diglycine) and N-acetylglycine, and to understand the nature of the interactions present on these systems. Experimentally, upon increasing the concentration of the salts, the solubility of N-acetylglycine decreased while the solubility of diglycine increased, with divalent cations inducing a greater salting-in on the solubility of diglycine than monovalent cations. For diglycine, the results from molecular dynamics simulations correlate well with the salting-in effect with interactions involving the cation and the carboxylate group, while for neutral N-acetylglycine the interactions between the chloride anion and the hydrogen atom of the carboxylic acid group, and between the carbonyl group of the peptide bond and the cation, can be exploited to describe the generalized salting-out effect.