With the goal of understanding how the nature of the tridentate macrocyclic supporting ligand influences the relative stability of isomeric mu-eta(2):eta(2)-peroxo- and bis(mu-oxo)dicopper complexes, a comparative study was undertaken of the O-2 reactivity of Cu(I) compounds supported by the 10- and 12-membered macrocycles, 1,4,7-R-3-1,4,7-triazacyclodecane (R(3)TACD; R = Me, Bn, iPr) and 1,5,9-triisopropyl-1,5,9-triazacyclododecane (iPr(3)TACDD). While the 3-coordinate complex [(iPr(3)TACDD)Cu]SbF6 was unreactive with O-2, oxygenation of [(R(3)TACD)Cu(CH3CN)]X (R = Me or Bn; X = ClO4-or SbF6-) at -80 degrees C yielded bis(mu-oxo) species [(R(3)TACD)(2)Cu2Cu2(mu-O)(2)]X-2 as revealed by UV-vis and resonance Raman spectroscopy. Interestingly, unlike the previously reported system supported by 1,4,7-triisopropyl-1,4,7-triazacyclononane (iPr(3)TACN), which yielded interconverting mixtures of peroxo and bis(mu-oxo) compounds (Cahoy, J.; Holland, P. L.; Tolman, W. B. Inorg. Chem. 1999, 38, 2161), low-temperature oxygenation of [(iPr(3)TACD)Cu(CH3CN)]SbF6 in a variety of solvents cleanly yielded a mu-eta(2): eta(2)-peroxo product, with no trace of the bis(mu-oxo) isomer. The peroxo complex was characterized by UV-vis and resonance Raman spectroscopy, as well as an X-ray crystal structure (albeit of marginal quality due to disorder problems. Intramolecular attack at the a C-H bonds of the substituents was indicated as the primary decomposition pathway of the oxygenated compounds through examination of the decay kinetics and the reaction products, which included bis(mu-hydroxo)- and mu-carbonato-dicopper complexes that were characterized by X-ray diffraction. A rationale for the varying results of the oxygenation reactions was provided by analysis of (a) the X-ray crystal structures and electrochemical behavior of the Cu(I) precursors and (b) the results of theoretical calculations of the complete oxygenated complexes, including all ligand atoms, using combined quantum chemical/molecular mechanics (integrated molecular orbital molecular mechanics, IMOMM) methods. The size of the ligand substituents was shown to be a key factor in controlling the relative stabilities of the peroxo and bis(mu-oxo) forms, and the nature of this influence was shown by both theory and experiment to depend on the ligand macrocycle ring size.