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.