Synthesis and Thermophysical Characterization of New Biologically Friendly Agmatine-Based Ionic Liquids and Salts by Experimental and Computational Approach

Abstract

© 2019 American Chemical Society. For the first time, the dicationic biological molecule agmatine in the synthesis of three novel ionic liquids, agmatine ibuprofenate, agmatine salicylate, and agmatine nicotinate, as well as of six salts, agmatine citrate, agmatine ascorbate, agmatine glutamate, agmatine m-hydroxybenzoate, agmatine nitrate, and agmatine chloride, was used. First of all, unknown acidity constants for agmatine were determined experimentally and by computational simulations. The synthesis was conducted by neutralization of agmatine hydroxide solution with relevant acids and then characterized by IR, NMR, TG, and DSC measurements. A cytotoxicity study of these compounds has been performed on the human nontumor cell line (normal fetal lung fibroblasts, MRC-5) and human caucasian colon adenocarcinoma (HT-29). The obtained results on MRC-5 cell lines declare the less toxic effect of synthesized ILs and salts compared to the environmentally and body friendly ascorbic acid. Thus, the obtained biocompatible ionic liquids and salts may be potentially beneficial for stabilizing bioactive compounds by improving solubility in aqueous media and biodistribution to target sites. The calculated binding energies between cation and anion for all compounds indicate weaker interactions in ionic liquid structures than in reported salts. This can cause easier and better dissociation of the ionic liquids and, hence, greater biological availability of both cation and anion in the organism. By virtue of the fact that the water has a key role in the living organism, solvation and taste properties for commercially available agmatine sulfate and synthesized agmatine chloride were discussed using obtained results from volumetric and viscosity measurements supported by computational simulation. The negligible effect of the anion nature on the conformation of agmatine cation has been proved in the investigated concentration range indicating that the difference between solvation properties of examined salts originates primarily from water organization around anion.