The unimolecular chemistry of [Cu(II)AA(AA – H)]⁺ complexes, composed of an intact and a deprotonated amino acid (AA) ligand, have been probed in the gas phase by tandem and multistage mass spectrometry in an electrospray ionization quadrupole ion trap mass spectrometer. The amino acids examined include Gly, Ala, Val, Leu, Ile, t-Leu and Phe. Upon collisionally-activated dissociation (CAD), the [Cu(II)AA(AA – H)]⁺ complexes undergo decarboxylation with simultaneous reduction of Cu(II) to Cu(I); during this process, a radical site is created at the α-carbon of the decarboxylated ligand (H₂N₁ – ^•C_αH – C_βH₂ – R; R = side chain substituent). The radical site is able to move along the backbone of the decarboxylated amino acid to form two new radicals (HN₁^• – C_αH₂ – C_βH₂ – R and H₂N₁ – C_αH₂ – ^•C_βH – R). From the complexes of Gly and t-Leu, only C_α and N₁ radicals can be formed. The whole radical ligand can be lost to form [Cu(I)AA]⁺ from these three isomeric radicals. Alternatively, further radical induced dissociations can take place along the backbone of the decarboxylated amino acid ligand to yield [Cu(II)AA(AA – 2H – CO₂)]⁺, [Cu(I)AA(^•NH₂)]⁺, [Cu(I)AA(HN = C_αH₂)]⁺, or [Cu(I)AA(H₂N – C_αH = C_βH – R′]⁺ (R′ = partial side chain substituent). The sodiated copper complexes, [Cu(II)(AA – H + Na)(AA – H)]⁺, show the same fragmentation patterns as their non-sodiated counterparts; sodium ion is retained on the intact amino acid ligand and is not involved in the CAD pathways. The amino groups of both AA units, the carbonyl group of the intact amino acid, and the deprotonated hydroxyl oxygen coordinate Cu(II) in square-planar fashion. Ab initio calculations indicate that the metal ion facilitates hydrogen atom shuttling between the N₁, C_α and C_β atoms of the decarboxylated amino acid ligand. The dissociations of the decarboxylated radical ions unveil important insight about the so far largely unknown intrinsic chemistry of α-amino acid and peptide radicals, which are implicated as intermediates in numerous pathogenic biological processes.

Keywords: Cu–amino acid complexes, a-amino acid radicals, H-atom shuttling, radical-induced fragmentation, reductive decarboxylation