Novel free radicals in synthetic and natural pheomelanins: distinction between dopa melanins and cysteinyldopa melanins by ESR spectroscopy.

Abstract

Synthetic pheomelanins from enzymic oxidation of the 3,4-dihydroxyphenylalanine (dopa) derivative 5-S-cysteinyldopa have been examined by ESR spectroscopy. These alkalisoluble polymers contain a novel kind of free radical that is spectroscopically distinct from that found in eumelanins. Delocalization of the unpaired electron onto a nitrogen atom and the ability of the radical to chelate complexing metal ions strongly suggest an o-semiquinonimine structure. The synthetic pheomelanin was compared with natural red pigments extracted from human red hair and from red chicken feathers. Spectroscopically, the chicken feather pheomelanin is almost identical to synthetic cysteinyldopa pheomelanin. In contrast, the pigment from red hair has a major spectral component very similar to that found in dopa melanin, with a smaller component corresponding to that found in cysteinyldopa melanin.Melanin pigmentation ofhair, skin, and eye is thought to result from two separate but biogenetically interrelated classes ofpigments: eumelanins (black-brown, insoluble in dilute alkali) and pheomelanins (yellow to reddish-brown, alkali soluble) (1). Eumelanins are generally considered to be derived from the enzymic oxidation of tyrosine through 3,4-dihydroxyphenylalanine (dopa) (structure I) (2), whereas pheomelanins arise by a diversion of the eumelanin pathway through the intervention of cysteine or related sulfhydryl compounds (3). A major intermediate in the biosynthesis of pheomelanins is the dopa metabolite 5-S-cysteinyldopa (structure II).

The physical and chemical properties of eumelanin

“…Natural melanin pigments typically contain a mixture of both types of free radicals, which some time makes difficult a precise determination of the contribution of orthosemiquinone and ortho-semiquinonimine radicals in the resulting paramagnetic properties. The ESR signal of pheomelanins, exhibits a distinct immobilized nitroxidelike features with the hyperfine coupling (2A zz ) of about 3.0 mT (Sealy et al, 1982b). The observed hyperfine coupling of pheomelanin ESR signal is due to a partial localization of the unpaired electron on the nitrogen atom of the ortho-semiquinonimine form of 1,4-benzothiazine subunits.…”

Melanins: Skin Pigments and Much More—Types, Structural Models, Biological Functions, and Formation Routes

“…Given the phototoxicity and the reported capacity to increase cancer risk of pheomelanin [160,162,163], this point is especially relevant for pale-skin individuals. The existence of some other factors related to pheomelanin but not to UV light exposition that also increase cancer risk has recently been proposed [164].…”

Photoprotection of human retinal pigment epithelium cells against blue light-induced apoptosis by melanin free radicals from Sepia officinalis

“…Electron spin polarization arises from the chemistry associated with radical production and depletion and is routinely detected by TREPR, a major tool for exploring free radical chemistry (32)(33)(34)(35)(36)(37). Although different melanins are distinguishable by conventional EPR spectroscopy (31,38), the free radical chemistry of melanin is complex and not well characterized, especially the chemistry of melanin that protects the RPE from light and ROS (18,20). Substantial evidence supports a phototoxic role of RPE melanin, especially in aged cells, including production of superoxide anions and hydroxyl radicals that are implicated in RPE cell death (39)(40)(41)(42)(43)(44)(45).…”