Protonation sequence of linear aliphatic polyamines from intramolecular atomic energies and charges

The analysis of intramolecular atomic energies and charges, obtained from QTAIM, strongly and unambiguously suggests that the most stable HL+ form of a linear triamine H2N(CH2)2NH(CH2)3NH2 (L) has the secondary nitrogen atom protonated, contradicting earlier reports. This is supported by the G(aq) value (at the RX3LYP/6-311++G(d,p) level of theory in solvent, CPCM/UAKS) which is lower by about 4 kcal mol−1 (equivalent to three log units of a protonation constant log KH) when compared with remaining HL+ tautomers. The most stable H2L2+ form of L found from QTAIM has two terminal nitrogen atoms protonated, which is in agreement with the existing views. A new rule governing the protonation sequence of linear polyamines is proposed stating that at thermodynamic equilibrium the protonation sequence in a solution results in the formation of tautomers which: (i) minimizes the differences in the atomic energies and net atomic charges of both terminal atoms, N and C, in all partially protonated forms, HL+ and H2L2+, and (ii) have a symmetrical distribution of the atomic energies and net atomic charges on the terminal fragments -CH2-NH2 of a linear molecule. Several conditions, involving the atomic energies and charges of the terminal N- and carbon atoms, are defined and incorporated in a protocol which results in a definite prediction of the protonation sequence of linear aliphatic triamines.