Binding of Divalent Metal Ions with Deprotonated Peptides:Do Gas-Phase Anions Parallel the Condensed Phase?

摘要

Chelation complexes of the histidine-containing tripeptides HisAlaAla, AlaHisAla, and AlaAlaHis with Ni(II) and Cu(II) having a −1 net charge are characterized in the gas phase by infrared multiple-photon dissociation (IRMPD) spectroscopy and density functional theory calculations. We address the question of whether the gas-phase complexes carry over characteristics from the corresponding condensed-phase species. We focus particularly on three aspects of their structure: (i) square-planar chelation by the deprotonated amide nitrogens around the metal ion (low-spin for the Ni case), (ii) metal-ion coordination of the imidazole side chain nitrogen, and (iii) the exceptional preference for metal-ion chelation by peptides with His in the third position from the N-terminus, as in the amino terminal Cu and Ni (ATCUN) motif. We find that square-planar binding around the metal ion, involving bonds to both deprotonated backbone nitrogens, one of the carboxylate oxygens and the N-terminal nitrogen, is the dominant binding motif for all three isomers. In contrast to the condensed-phase behavior, the dominant mode of bindingfor all three isomers does not involve the imidazole side chain, whichis instead placed outside the coordination zone. Only for the AlaAlaHisisomer, the imidazole-bound structure is also detected as a minoritypopulation, as identified from a distinctive short-wavelength IR absorption.The observation that this conformation exists only for AlaAlaHis correlateswith condensed-phase behavior at neutral-to-basic pH, in the sensethat the isomer with His in the third position is exceptionally disposedto metal ion chelation by four nitrogen atoms (4N) when compared withthe other isomers. These results also emphasize the divergence betweenthe conformational stabilities in the gas phase and in solution orcrystalline environments: in the gas phase, direct metal binding ofthe imidazole is overall less favorable than the alternative of aremote imidazole that can act as an intramolecular H-bond donor enhancingthe gas-phase stability.