Peptide bond tautomerization induced by divalent metal ions: characterization of the iminol configuration.

A metal ion that attaches to a peptide backbone has the choice of binding to an amide carbonyl oxygen atom or to an amide nitrogen atom by replacement of the amide proton. Coordination to the nitrogen atom is normally accompanied by elimination of the proton, thereby resulting in deprotonation of the ligand. An alternative possibility, not involving deprotonation, is the unusual amide/iminol tautomerization. In the gas phase, outright elimination of the proton is energetically costly, so that metal complexation without deprotonation is frequently observed and could well be accompanied by tautomerization. The present results show that coordination of active metal ions to amide nitrogen atoms through iminol tautomerism (analogous to the wellknown keto/enol tautomerism of ketones) can indeed be a favorable gas-phase binding pattern. Such a chemical change is readily identified by infrared multiple-photon dissociation (IRMPD) spectroscopy, which is an emerging tool for structural investigation of gas-phase complexes of selected masses and which uses powerful new IR laser sources. We apply this tool to investigate the possible conformations of gas-phase complexes that are composed of model dipeptides with active divalent metal ions generated by electrospray ionization. The complexes characterized herein bridge the conceptual division between simple complexation and complexation with deprotonation. In fact the complexes are shown to contain the metal/amidenitrogen bond, but without concurrent deprotonation. We have previously investigated complexation of alkali and alkaline-earth ions by the dipeptide PhePhe, which provides a good model for interaction of ions with the peptide amide linkage and gives insight into stabilization and structure determination through cation–p interactions. This dipeptide readily forms + 2 complexes with divalent metal ions. The binding patterns of interest are shown in Scheme 1. Charge-solvated (CS) binding, pattern I, is normal for alkalimetal ions and tends to maximize the number of coordinated