NA- BOND-ENERGIES, ENTROPIES OF NA+ COMPLEXATION, AND ATTACHMENT SITES FROM THE DISSOCIATION OF NA+-BOUND HETERODIMERS AND AB-INITIO CALCULATIONS( BINDING TO CYCLIC AND LINEAR DIPEPTIDES )

The Na+ affinities of simple cyclic and linear dipeptides and of selec ted derivatives are determined in the gas-phase based on the dissociat ions of Na+-bound heterodimers [peptide + B-i]Na+, in which B-i repres ents a reference base of known Na+ affinity (kinetic method). The deco mpositions of [peptide + B-i]Na+ are assessed at three different inter nal energies; this approach permits the deconvolution of entropic cont ributions from experimentally measured free energies to thus obtain af finity (i.e. enthalpy or bond energy) values. The Na+ affinities of th e peptides studied increase in the order (kJ mol(-1)) cyclo-glycylglyc ine (143) < cyclo-alanylglycine (149) < cyclo-alanylalanine (151) < N- acetyl glycine (172) < glycylglycine (177) < alanylglycine (178) < gly cylalanine (179) < alanylalanine (180) < glycylglycine ethyl ester (18 1) < 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+ complexatio n alters rotational degrees of freedom either in the peptide or in B-i . From the relative bond entropies, it is possible to appraise absolut e 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 dipep tides bind Na+ in a monodentate fashion through one of their amide car bonyl oxygens, while the linear molecules coordinate Na+ in a multiden tate 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 ch elation of Na+ by the two carbonyls and concomitant formation of a hyd rogen bond between the amino group and the amide nitrogen. Such a stru cture agrees very well with the experimental enthalpy and entropy tren ds observed for the linear molecules. According to theory, zwitterioni c forms of [glycylglycine]Na+ are the least stable isomers, as also su ggested by the experimental results.