The 1:1 inclusion complex of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphinato iron(II) (Fe(II)TPPS) and an O-methylated beta-cyclodextrin dimer having a pyridine linker (1) binds dioxygen reversibly in aqueous solution. The O2 adduct was very stable (t(1/2) = 30.1 h) at pH 7.0 and 25 degrees C. ESI-MS and NMR spectroscopic measurements and molecular mechanics (MM) calculations indicated the inclusion of the sulfonatophenyl groups at the 5- and 15-positions of Fe(III)TPPS or Fe(II)TPPS into two cyclodextrin moieties of 1 to form a supramolecular 1:1 complex (hemoCD1 for the Fe(II)TPPS complex), whose iron center is completely covered by two cyclodextrin moieties. Equilibrium measurements and laser flash photolysis provided the affinities ( and ) and rate constants for O2 and CO binding of hemoCD1 (k(O2)(on), k(O2)(off), k(CO)(on), and k(CO)(off)). The CO affinity relative to the O2 affinity of hemoCD1 was abnormally high. Although resonance Raman spectra suggested weak back-bonding of d(pi)(Fe) --> pi(CO) and hence a weak CO-Fe bond, the CO adduct of hemoCD1 was very stable. The hydrophobic CO molecule dissociated from CO-hemoCD1 hardly breaks free from a shallow cleft in hemoCD1 surrounded by an aqueous bulk phase leading to fast rebinding of CO to hemoCD1. Isothermal titration calorimetry furnished the association constant (K(O2)), DeltaH degrees , and DeltaS degrees for O2 association to be (2.71 +/- 0.51) x 10(4) M(-1), -65.2 +/- 4.4 kJ mol(-1), and -133.9 +/- 16.1 J mol(-1) K(-1), respectively. The autoxidation of oxy-hemoCD1 was accelerated by H+ and OH-. The inorganic anions also accelerated the autoxidation of oxy-hemoCD1. The O2-Fe(II) bond is equivalent to the O2.--Fe(III) bond, which is attacked by the inorganic anions or the water molecule to produce met-hemoCD1 and a superoxide anion.