Na⁺ binding to cyclic and linear dipeptides. Bond energies, entropies of Na⁺ complexation, and attachment sites from the dissociation of Na⁺-bound heterodimers and ab initio calculations

The Na⁺ affinities of simple cyclic and linear dipeptides and of selected derivatives are determined in the gas-phase based on the dissociations of Na⁺-bound heterodimers [peptide + B(i)]Na⁺, in which B(i) represents a reference base of known Na⁺ affinity (kinetic method). The decompositions of [peptide + B(i)]Na⁺ are assessed at three different internal energies; this approach permits the deconvolution of entropic contributions from experimentally measured free energies to thus obtain affinity (i.e. enthalpy or bond energy) values. The Na⁺ affinities of the peptides studied increase in the order (kJ mol^-1) cyclo-glycylglycine (143) < cyclo-alanylglycine (149) < cyclo-alanylalanine (151) < N-acetyl glycine (172) < glycylglycine (177) < alanylglycine (178) < glycylalanine (179) < alanylalanine (180) < glycylglycine ethyl ester (181) < glycylglycine amide (183). The method used provides quantitative information about the difference in bond entropies between the peptide-Na⁺ and B(i)-Na⁺ bonds, which is most significant when Na⁺ complexation alters rotational degrees of freedom either in the peptide or in B(i). From the relative bond entropies, it is possible to appraise absolute entropies of Na⁺ attachment, which are ~104 and ~116 J mol^-1 K^-1 for the cyclic and linear molecules, respectively. The combined affinity and entropy data point out that the cyclic dipeptides bind Na⁺ in a monodentate fashion through one of their amide carbonyl oxygens, while the linear molecules coordinate Na⁺ in a multidentate arrangement involving the two carbonyl oxygens and, possibly, the N-terminal amino group. High-level ab initio calculations reveal that the most stable [glycylglycine]Na⁺ structure arises upon bidentate chelation of Na⁺ by the two carbonyls and concomitant formation of a hydrogen bond between the amino group and the amide nitrogen. Such a structure agrees very well with the experimental enthalpy and entropy trends observed for the linear molecules. According to theory, zwitterionic forms of [glycylglycine]Na⁺ are the least stable isomers, as also suggested by the experimental results.