Biomedical overview of melanin. 2. Updating molecular modeling, synthesis mechanism, and supramolecular properties regarding melanoma therapy

Abstract

Melanins represent one of the most ancient and important group of natural macromolecular pigments. They have multiple biological roles in almost all organisms across the Phyla, examples being photoprotection, anti-oxidative action, radical scavenger activity, and heavy metal removal. From the biomedical point of view, melanocytes are involved in the origin of melanoma tumors, and the main therapeutic advances for their treatment have been revisedin Part 1 of this review. The chemical structure of eumelanin is a biological concern of great importance, and therefore, exploring theoretical molecular models and synthesis mechanisms will be here described, as well as molecular orbital features and supramolecular organization, which are responsible for the key properties that make these biological pigments so important, and so fascinating. Ultimately, this updated overview is devoted to describe present structural models and physico-chemical characteristics of eumelanin, in order to explain and utilize melanin properties on which new photothermal and ultrasonic protocols for melanoma treatment can be devised and applied.

Molecular Modeling of Phenyl-Boronic Acids and Catechol-Borate Esters: A Mechanistic Rationale for Boron Binding to Melanin Catechols, Regarding the 10Boron Neutron-Capture Therapy of Melanoma

“…As they are acidic organelles with a clear lysosome lineage [55] and intramelanosomal pH range of 3-5 [56], the occurrence of negatively charged borate esters of eumelanin is unlikely to occur in living melanocytes. Regarding the recently proposed catechol-porphycene (CPo) model [32,33], it must be noted that this structure fulfills all characteristic features of natural and synthetic eumelanins, appearing as a multilayer graphitic structure. Modeling of a planar tetra-CPo molecule with catechol-attached PBA residues illustrates the possible organization of the polymer (Figure 5).…”

“…The chemical structures of model compounds that will be analyzed, namely catechol-borate and phenyl-boronic acid, are shown in Figure 1. Concerning the chemistry of melanin and its precursors, several reviews have been published on melanin structure and its biosynthesis [28][29][30], being the most representative structure the porphyrin-like graphitic model from Olivieri and Nicolaus [31], and also the recent poly-catecholporphycene (poly-CPo) model [32,33], based on the Olivieri and Nicolaus structure [31].…”

“…Eumelanin contains a great amount of catechol groups [28,33,[46][47][48], which can react with borate anions and boronic acids (see Figure 1). Borate-ligand 1:1 and 1:2 complexes are the most and less usual, respectively [25,27], which could difficult the occurrence of borate 1:2 complexes using melanin catechols.…”

Melanin-Binding Colorants: Updating Molecular Modeling, Staining and Labeling Mechanisms, and Biomedical Perspectives

“…In plants and fungi, melanins generally correspond to the catechol-type (allomelanins) [22]. Early and recent reviews deal with the main features of melanin chemistry, properties, and applications [19,[23][24][25][26][27][28][29][30][31][32][33].…”

“…A model based in a benzoquinone-porphycene (BQPo) macrocycle has been suggested [45][46][47]. It could fulfill most characteristics of eumelanin [33], namely a graphite-like structure with broad-band light absorption, semi-and photo-conductivity, strong binding affinity for dyes and drugs, and electron microscopic and X-ray crystallographic features.…”