Formation of metal complex ions from amino acid in the presence of Li+, Na+ and K+ by electrospray ionization: metal replacement of hydrogen in the ligands

Alkali metal cations easily form complexes with proteins in biological systems; understanding amino acid clusters with these cations can provide useful insight into their behaviors at the molecular level including diagnosis and therapy of related diseases. For the purpose of characterization of basic interaction between amino acids and alkali metal, each of the 20 naturally occurring amino acids were ionized in the presence of lithium, sodium and potassium cations by electrospray ionization, and the resulting product ions were analyzed. We focus our attention on the gas phase alkali metal ion-proton exchanged complexes in current study, specifically complexes with serine, threonine, asparagine and glutamine, which share characteristic pattern unlike other amino acids. All amino acids generated M + H](+) and M + Na](+) ions, where M stands for the neutral amino acid. Serine, threonine, asparagine and glutamine generated cluster ions of nM - nH + (n + 1)Na](+) and nM - (n - 1)H + (n - 1)Na + K](+) , where n = 1-7. While the (M - H + Li) and (M - H + K) species were not observed, the neutral (M - H + Na) species formed by proton-sodium cation exchange had a highly stable cyclic structure with ketone and amine ligand sites, suggesting that (M - H + Na) serves as a building block in cluster ion formation. Cluster ion intensity distributions of nM - nH + (n + 1)Na](+) and nM - (n - 1)H + (n - 1)Na + K](+) showed a magic number at n = 3 and 4, respectively. Extensive B3LYP-DFT quantum mechanical calculations were carried out to elucidate the geometry and energy of the cluster ions, and they provided a reasonable explanation for the stability and structure of the cluster ions.