In this article spectrophotometry is applied to measure the saturated solubility of some nucleobases in aquo-organic solvent mixtures of protic ethylene glycol at five equi-distant temperatures from 288.15 to 308.15 K under experimental pressure, p = 0.1 MPa. Standard Gibbs energies $$[\Delta G_{\text{t}}^{^\circ } (i)]$$ and entropies $$[T\Delta S_{\text{t}}^{^\circ } (i)]$$ of transfer from water to aqueous mixture of protic ethylene glycol have been evaluated at 298.15 K. The chemical contributions of these energetics $$[\Delta G_{\text{t,chem}}^{^\circ } (i)]$$ and $$[T\Delta S_{\text{t,chem}}^{^\circ } (i)]$$ of the involved nucleic acid bases have been computed by subtracting the cavity effect, dipole–dipole and dipole-induced dipole type interaction effects. The chemical composition of transfer energetics of nucleo bases is guided by different effects like dispersion interaction, basicity-acidity, hydrogen bonding, hydrophobic and hydrophilic interaction effects of aqueous ethylene glycol as compared to that of the reference solvent, water. The cavity effect has been estimated by using the Scaled Particle Theory. Computation of dipole–dipole and dipole-induced interactions has been performed using Keesom orientation expressions. The trend of variation of Gibbs energies due to chemical interactions are guided by decreased hydrophobic hydration (HbH), increased acidity and dispersion effects of aqueous ethylene glycol solvent mixtures as compared to the reference solvent, water.