Macrocyclic effect of auxiliary ligand on the gas‐phase dissociation of ternary copper(II)–GGX complexes

Previous studies into the dissociation of [Cu II (dien)peptide] . 2+ ions (dien = diethylenetriamine) have shown that NH‐containing auxiliary ligands do not favor the formation of [peptide] . + species; instead, they promote proton‐transfer reactions, especially for peptides containing basic amino residues. Formation of radical cationic tripeptides of the form GGX . + [GGX = glycylglycyl(residue X)] becomes feasible upon substituting the open‐chain tridentate ligand dien with its analogous cyclic ligand, 1,4,7‐triazacyclononane (9‐aneN 3 ); i.e., from [Cu II (9‐aneN 3 )GGX] . 2+ ions. Similar enhancements occur when using 1,4,7,10‐tetraoxacyclododecane (12‐crown‐4) in place of its open‐chain analog, 2,5,8,11‐tetraoxadecane (triglyme). We have demonstrated that a sterically encumbered auxiliary macrocyclic ligand within [Cu II (L)GGX] . 2+ complex ions [where L = 9‐aneN 3 or 12‐crown‐4] facilitates the formation of radical cationic peptides through gas‐phase fragmentation. We verified our experimental observations by examining the reactivities of a series of 19 tripeptides of the type GGX that differ only in the identity of their C‐terminal residue. The energy of the electron‐transfer reaction correlates well with the bond‐dissociation energy of the peptide–Cu(II) interaction; the presence of a constrained macrocyclic ligand weakens metal–peptide chelation through steric repulsion between the ligand and the peptide, and this situation may lead to more favorable radical cationic peptide formation.