Prediction of microscopic protonation constants of polybasic molecules via computational methods: A complete microequilibrium analysis of spermine

For the first time, a simple methodology is reported for theoretical calculation of microscopic protonation constants of polybasic molecules in solution. Density functional theory study was used for complete microequilibrium analysis of spermine, H₂N(CH₂)₃NH(CH₂)₄NH(CH₂)₃NH₂, a linear tetraamine with 16 known microspecies. A general thermodynamic cycle is proposed to calculate protonation microconstants of polybasic molecules using calculated micro‐ΔG values in aqueous solution. The microscopic protonation constants were determined with considering both the most abundant and most stable conformers for all microspecies. The results show that the microscopic protonation constants derived from the most abundant conformers (i.e., linear conformers in which the intramolecular hydrogen bonding does not exist) are in good agreement with the corresponding available experimental data. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011