Complexation of cytosine, uracil and thymine with the dipeptides glycyl-glycine, glycyl-l-phenylalanine, alanyl-l-glutamine and with the tripeptide γ-l-glutamyl-l-cysteinyl-glycine in a buffered saline has been studied using dissolution calorimetry. The values of the reaction constant, the change in Gibbs energy, enthalpy, and entropy have been found (log Kr, ΔrG, ΔrH, TΔrS). By analyzing the obtained data together with previous results for other peptides, it was found that peptides bind to pyrimidine nucleic bases in a solution in several important patterns. No pattern depending on the charge of the peptide is observed in the obtained thermodynamic values, which indicates a minor role of electrostatic interaction in their binding by the nucleic base. The effect of the structure of the peptide and the nucleobase on the thermodynamic parameters of complexation is manifested in the fine balance of the enthalpy and entropy factors of the process. The Gibbs energy of complexation depends on the number of potential H-bonding sites of the peptide, which shows the major contribution of H-bonding between the reagents. The reduction in the favorable entropy factor is responsible for the tendency of negative ΔrG values to decrease with increasing number of sites. It was found that positive values of entropy change during complex formation increase with increasing hydrophobicity index of the peptide, which is interpreted within the framework of the overlapping hydration sphere model. Strengthening the hydrophobic properties of the nucleic base from uracil to thymine due to the additional CH3 group slightly changes the enthalpy and entropy of the process of binding the +AlaGln− zwitterion but significantly affects the thermodynamic parameters of binding the anion of peptide +/−GluCysGly−.
