Water‐Soluble Melanin–Protein–Fe/Cu Conjugates Derived from Norepinephrine as Reliable Models for Neuromelanin of Human Brain Locus Coeruleus

Abstract

Water-soluble melanin-protein-Fe/Cu conjugates derived from norepinephrine and fibrillar β-lactoglobulin are reliable models for neuromelanin (NM) of human brain locus coeruleus. Both iron and copper promote catecholamine oxidation and exhibit strong tendency to remain coupled in oligonuclear aggregates. The Fe-Cu clusters are EPR silent and affect the 1 H NMR spectra of the conjugates through a specific sequence of signals. Derivatives containing only Fe or Cu exhibit different NMR patterns. The EPR spectra show weak signals of paramagnetic Fe III in conjugates containing Fe or mixed Fe-Cu sites due to small amounts of mononuclear centers. The latter derivatives exhibit EPR signals for isolated Cu II centers. These features parallel the EPR behavior of NM from locus coeruleus. The spectral data indicate that Fe III is bound to the melanic fraction, whereas Cu II is bound on the protein fibrils, suggesting that the Fe-Cu clusters occur at the interface between the two components of the synthetic NMs.

Melanin: insights into structure, analysis, and biological activities for future development

“…24,49 Neuromelanin, like other melanin, has the highest absorption peak between 200 and 300 nm, showing a monotonic absorption curve decreasing gradually to the visible range. 70 While UV-vis absorption spectroscopy has proven to be a useful tool for melanin quantification, it is not without its limitations. One of the main challenges in this regard is the potential interference from other pigments and chromophores present in the sample.…”

“…51 200-300 nm: maximum absorbance, showing a monotonic absorption curve decreasing gradually to the visible range. 70 Thiazole-4,5-dicarboxylic acid (TDCA)/pyrrole-2,3,5tricarboxylic acid (PTCA) ratio. 71 Typical quinone structure, an aromatic structure and aliphatic moieties.…”

“…24,49 Neuromelanin, like other melanin, has the highest absorption peak between 200 and 300 nm, showing a monotonic absorption curve decreasing gradually to the visible range. 70…”