Dioxgyen (O2) activation and reduction are not only vital for aerobic life, but also essential to industrial applications such as sustainable fuel cells. Dioxgyen is clean, abundant, and a powerful four-electron oxidant, but also kinetically inert and requires activation. In Nature, the activation of O2 is often facilitated by transition metal centers at metalloenzyme active sites. For example, during the cellular respiration reaction, mitochondrial Cytochrome c Oxidase (CcO) utilizes a unique heme-copper binuclear active site to carry out the enzymatic four-electron four-proton reduction of O2 to water. This reaction is coupled with the process of proton pumping and the biological ATP production. While the mechanistic investigations of CcO over a period of five decades have led to significant insight into the cooperative O2 chemistry at the iron/copper sites, the vital aspects of the oxidized/resting state of CcO for its enzymatic function is yet to be understood. Moreover, the examples of such cooperative O2 chemistry at heterobinuclear centers are only limited to heme/copper assemblies. Our research goal is to contribute to a fundamental understanding of the delicate cooperativity of the two different metal centers in O2 chemistry. This seminar will focus on our recent studies looking into how the cooperativity triggers formation of new intermediates and reactivities.