Boundaries among biological, chemical and physical domains are nowadays fading, and the complex phenomena observed in Nature as well as in artificial systems can only be tackled from a broader/interdisciplinary perspective. In this context, the biological activation of the molecular oxygen is a fascinating and yet complex process. The ability to store, transport and utilize this simple molecule gated evolution of life in our planet and led to growth and selection of a variety of organisms. Complex molecules selected by Nature as active in “key metabolic paths” of the oxygen in life often contain copper and/or iron metal ions as reactive centres. A wide variety of experimental results and theoretical investigations show that the metallo-oxygen interactions have dominant states that are not spatially homogeneous (anisotropy). These effects occur when a number of physical interactions such as spin, charge, lattice (crystal-field), and/or orbitals are simultaneously active. The result of these interlocked numbers of factors links biology to chemistry and molecular physic, and allow the oxygen to be used in different ways within metabolism. The research proposal presented herein aims to investigate the red/ox mechanism and the connected energetic of the oxygen activation process in a series of di-iron (Ribonucleotide Reductase, RNR, Class I R2) and copper protein (multicopper oxidases) through the use of spectroscopic methods (EPR X-Q, high field EPR, CD, MCD, rR resonance Raman), structural (X-ray) and kinetic analyses (stopped flow, cryoenzymology). The endeavour is directed towards a better understanding of the geometric and electronic structure of metal-oxygen interactions that contribute to define O2 reactivity. These studies will provide molecular level insight into oxygen and metal metabolism, disease states, bioremediation and possible the development of efficient drugs inhibitor.