Biomimetic pheomelanin to unravel the electronic, molecular and supramolecular structure of the natural product

Herein, we investigate synthetic routes to a close mimic of natural pheomelanin. Three different oxidative polymerization routes were attempted to generate synthetic pheomelanin, each giving rise to structurally dissimilar materials. Among them, the route employing 5-cysteinyl-dihydroxyphenylalanine (5-CD) as a monomer was verified as a close analogue of extracted pheomelanin from humans and birds. The resulting biomimetic and natural pheomelanins were compared via various techniques, including solid-state Nuclear Magnetic Resonance (ssNMR) and Electron Paramagnetic Resonance (EPR). This synthetic pheomelanin closely mimics the structure of natural pheomelanin as determined by parallel characterization of pheomelanin extracted from multiple biological sources. With a good synthetic biomimetic material in hand, we describe cation-pi interactions as an important driving force for pheomelanogenesis, further advancing our fundamental understanding of this important biological pigment.

Automated summary

In this study, we explored different synthetic routes to create a mimic of natural pheomelanin. Among the three attempted oxidative polymerization routes, the one using 5-cysteinyl-dihydroxyphenylalanine (5-CD) as a monomer proved to be the closest analogue to extracted pheomelanin from humans and birds. The resulting synthetic pheomelanin was compared to natural pheomelanin using various techniques, showing a close resemblance in structure. This research contributes to our understanding of the important biological pigment by revealing the role of cation-pi interactions in pheomelanogenesis.