Molecular modeling, pK a and thermodynamic values of asthma drugs

Abstract

This study investigates on optimized structure, pK a values and thermodynamic properties of four asthma drugs, e.g., salbutamol, terbutaline, salmeterol, and formoterol, in aqueous solution using ab initio and DFT methods at different temperatures. The molecular conformations and solute–solvent interactions of the cations, neutrals, and anions molecules of the drugs were investigated. Further, the best ionization reaction and Tomasi’s method at the B3LYP/6-31 + G(d) level of theory were used to calculate ∆G and pK a values. For the validation, the pK a values and ionization mechanisms of salbutamol and terbutaline are calculated. Furthermore, ionization schemes are proposed for formoterol and salmeterol drugs, and their pK a values at different temperature are calculated. Moreover, the chemical reactions tendency calculation showed that net electrophilicity of terbutaline, the chemical potential of salbutamol, and electronegativity of formoterol were more than the other four asthma drugs in this work. Theoretical calculation of HOMO–LUMO gap shows that the maximum and minimum gaps were for salbutamol and terbutaline, respectively. Besides, charge density distribution and site of chemical reactivity of the asthma drugs are studied by mapping electron density isosurface with molecular electrostatic potential (MEP). Also, thermodynamic properties of the drugs in aqueous solution show negative values for ∆S and positive values for ∆G.