Structural characterizations of histidine-containing tripeptides complexed with zinc and cadmium dications using IRMPD spectroscopy and theoretical calculations

Metalated gas-phase complexes, M²⁺(HisAlaAla), M²⁺(AlaHisAla), and M²⁺(AlaAlaHis), where M = Zn and Cd, were examined using infrared multiple photon dissociation (IRMPD) spectroscopy with light from a free-electron laser (FEL). These complexes were chosen because they provide model systems for metal binding to proteins. Complementary simulated annealing calculations were performed to determine energetically low-lying conformers and isomers of these structures. Quantum chemical calculations were used to optimize the structures at the B3LYP level of theory using 6-311+G(d,p) and def2-TZVP basis sets for zinc and cadmium complexes, respectively. IRMPD and calculated linear absorption spectra were compared to evaluate which structures are present. Relative energies of the various species were evaluated using single-point energy calculations for low-lying structures at the B3LYP, B3P86, and MP2(full) levels using 6-311+G(2d,2p) and def2-TZVPP basis sets. For species with histidine at a terminal position (AAH or HAA), the conformations that best reproduce the IRMPD spectra are charge-solvated (CS) conformers, where the metal dication binds to the amine and carbonyl groups of the peptide backbone and to the nitrogen of the histidine side chain, along with contributions from an iminol structure for AAH. The species with the histidine in the center position (AHA) adopt an iminol structure, where the metal dication binds to the backbone iminol nitrogens, the α-amine, π-imine, and the carbonyl of the C-terminus.