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 similar to 104 and similar to 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.