By means of a combined experimental and computational approach, we show that a 2D metal-organic framework selfassembled at the Au(111) termination is able to mimic the O 2 stabilization and activation mechanisms that are typical of the biochemical environment of proteins and enzymes. 5,10,15,20-tetra(4-pyridyl)21H,23H-porphyrin cobalt(III) chloride (CoTPyP) molecules on Au(111) bind dioxygen forming a covalent bond at the Co center, yielding charge injection into the ligand by exploiting the surface trans-effect. A weakening of the O-O bond occurs, together with the development of a dipole moment, and a change in the molecule's magnetic moment. Also the bonding geometry is similar to the biological counterpart, with the O 2 molecule sitting on-top of the Co atom and the molecular axis tilted by 118°. The ligand configuration lays between the oxo-and the superoxo-species, in agreement with the observed O-O stretching frequency measured in situ at near-ambient pressure conditions.