Thermal decomposition of peroxidized coelenterazines with and without external perturbations has been studied theoretically using the hybrid density functional theory (B3LYP) and the Coulomb-attenuating method (CAM). Possible roles of a hydrogen-bonding interface constituted by amino acid residues in the coelenterazine-biding site of aequorin are addressed by using simple model clusters with a polarizable continuum model to grasp some important aspects that may affect the electronic mechanism operating within the photoprotein. Calculations have revealed that the electronic property and stability of the peroxide are greatly affected by its protonation state and/or environmental effects, such as a polarizing medium and specific (localized) short-range electrostatic interactions, which may be critical for the bioluminescence activity. Theory highlights two mechanisms by which the neutral species can be activated, which otherwise decomposes by a homolytic O-O dissociation with a high barrier. In the first mechanism, the Tyr82-His 16-Trp86 triad motif facilitates the deprotonation process of the phenolic OH group at the C-6 position of the coelenterazine and thereby makes it a sufficiently good electron donor to activate the O-O bond. In the second mechanism, intramolecular charge transfer is accomplished within the neutral peroxide by a proton delivery mediated via another triad motif, Tyr 184-His 169-Trp 173, without the activation of the Substrate itself. The combination of the first and second mechanisms leads to complete electron transfer for the formation of a radical pair as a local intermediate stabilized by the nearby triad motifs.