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

Abstract

Melanin and melanoma tumors are two fields of increasing interest in biomedical research. Melanins are ubiquitous biopigments with adaptive value and multiple functions, and occur in the malignant melanoma. Although several chemical structures have been proposed for eumelanin, molecular modeling and orbitals indicate that a planar or spiral benzoquinone-porphycene polymer would be the model that better explains the broad-band light and ultrasound absorption, electric conductivity, and graphite-like organization shown by X-ray crystallography and electron microscopy. Lysosomes and melanosomes are selectively labeled by vital probes, and melanin also binds to metal cations, colorants, and drugs, with important consequences in pharmacology, pathology, and melanoma therapy. In addition to traditional and recent oncologic treatments, photodynamic, photothermal, and ultrasound protocols represent novel modalities for melanoma therapy. Since eumelanin is practically the ideal photothermal and ultrasound sensitizer, the vibrational decay from photo-excited electrons after NIR irradiation, or the electrochemical production of ROS and radicals after ultrasound absorption, induce an efficient heating or oxidative response, resulting in the damage and death of tumor cells. This allows repetitive treatments due to the remaining melanin contained in tumoral melanophages. Given that evolution and prognosis of the advanced melanoma is still a concern, new biophysical procedures based on melanin properties can now be developed and applied.

Diphenyl-Furanones and Diphenyl-Oxopyrrole Derivatives: From Analytical Reagents for Amino Groups to New Fluorochromes for Cytochemical Staining of Chromatin DNA and Chromosomes: Proposal for Intercalative Binding and Fluorescence Mechanism

“…Molecular modeling studies on protonated diPOPy (diPOPy-H), diPOPy-G, and bis-diPOPy-Sp intercalated into an AT-DNA tetramer, as well as fluorescamine and its reaction products with amino groups (BzPOPy), were carried out using the HyperChem v7 and v8.0.10 software (Hypercube, Inc., Gainesville, USA). As performed in previous molecular modeling studies [52,53], geometry optimization was achieved with the MM+ routine, followed by energy minimization by either the semi-empirical PM3 method (Polak-Ribière conjugate gradient) converged at 1, 0.5, 0.2, or 0.1 kcal/(Å mol), or using the extended Hückel method.…”

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

“…Following previous studies on modeled chemical structures [30,[34][35][36][37][38], the use of chemical drawn, and molecular modeling software allowed to analyze and illustrate the structure of some boron-containing agents. Chemical structures with formal double bonds were drawn with ChemDraw Ultra v12.0 software.…”

“…It is conceivable that the great amount of catechol groups makes melanin a suitable substrate to form borate esters, but the simple binding mechanism of boronic acids to melanin catechols have been mostly overlooked. Although a role as melanin precursor for BPA cannot be excluded, the main action mechanism could be a direct chemical reaction with suitable substrates such as aromatic diols, as seems to occur in the case of some melanoma seekers [37].…”

Prebiotic RNA Engineering in a Clay Matrix: Molecular Modeling Rationale and Mechanistic Proposals for Explaining Helicity, Antiparallelism and Prebiotic Replication of Nucleic Acids

“…To substantiate molecular structures and events, simple molecular modeling methods were performed following previous studies to generate computerdrawn skeletal (wire), ball-and-stick, and spacefilling (atomic volume) models [39][40][41] . More accurate methods such as density functional theory (DFT) to calculate mechanical properties of peptide and protein are complex and expensive [42] , and they were not applied.…”

“…Fused lobes with the same color are in-phase, and those with isolated (unfused) lobes are out of-phase. The analysis of MOs is especially suitable to reveal the coupling of LUMO states in stacked molecules, which expands the excited π-electron resonance along the vertical stacking axis [39][40][41] .…”