The dissociation of [Cu II (L)His] •2+ complexes [L = diethylenetriamine (dien) or 1,4,7-triazacyclononane (9-aneN 3 )] bears a strong resemblance to the previously reported behavior of [Cu II (L)GGH] •2+ complexes. We have used low-energy collision-induced dissociation experiments and density functional theory (DFT) calculations at the B3LYP/6-31+G(d) level to study the macrocyclic effect of the auxiliary ligands on the formation of His •+ from prototypical [Cu II (L)His] •2+ systems. DFT revealed that the relative energy barriers of the same electron-transfer (ET) dissociation pathways of [Cu II (9-aneN 3 )His] •2+ and [Cu II (dien)His] •2+ are very similar, with the ET reactions of [Cu II (9-aneN 3 )His] •2+ leading to the generation of two distinct His •+ species; in contrast, the proton transfer (PT) dissociation pathways of [Cu II (9-aneN 3 )His] •2+ and [Cu II (dien)His] •2+ differ considerably. The PT reactions of [Cu II (9-aneN 3 )His] •2+ are associated with substantially higher barriers (>13 kcal/mol) than those of [Cu II (dien)His] •2+ . Thus, the sterically encumbered auxiliary 9-aneN 3 ligand facilitates ET reactions while moderating PT reactions, allowing the formation of hitherto nonobservable histidine radical cations.