From Monomers to Aggregates: The Influence of Redox State and Structure on the First Excited States of Eumelanin and Pheomelanin

Melanin pigments protect human tissues from ultraviolet and visible radiation, yet their phototoxic potential increases with oxidative degradation. This computational study investigates how the oxidation state influences the first excited states of eu- and pheomelanin using molecular models of varying complexity (monomers to tetramers, both covalently and non-covalently bonded). First, vertical and adiabatic electronic transitions were computed, and supramolecular interactions were characterized with the ETS-NOCV method. In eumelanin, oxidation drastically lowers the first triplet-state (T1) energies (from above 230 kJ/mol) to levels comparable to retinal carotenoids (≤66 kJ/mol), emphasizing its role in triplet quenching rather than singlet oxygen generation. Pheomelanin showed greater heterogeneity in the values of the first triplet state, staying mostly above the eumelanin T1 energies. However, selected pheomelanin structures also exhibited relatively low triplet energies, particularly oxidized benzothiazole (BZox) and trichochromes, and although their T1 energetics remained higher than those calculated for oxidized eumelanin, they were still sufficiently low to suggest a potential ability to quench singlet oxygen. Furthermore, supramolecular analysis reveals that eumelanin aggregates are moderately stabilized by both π-π stacking and hydrogen bonding, whereas pheomelanin aggregates are dominated by dense hydrogen-bond networks.