Acridine orange fluorescence in chromosome cytochemistry: Molecular modeling rationale for understanding the differential fluorescence on double- and single-stranded nucleic acids

Many fluorophores display interesting features that make them useful biological labels and dyes, particularly in Cell Biology and Cytogenetics. Changes in the absorption-emission spectra (ortho- and metachromasia) are accounted among them. Acridine orange (AO) is one of such fluorochromes with an ex...

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Detalles Bibliográficos
Autores: Blázquez Castro, Alfonso, Stockert, Juan C.
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/717303
Acceso en línea:http://hdl.handle.net/10486/717303
https://dx.doi.org/10.1016/j.acthis.2024.152225
Access Level:acceso abierto
Palabra clave:Acridine Orange
Chromosomes
Double-Stranded DNA
Metachromatic Fluorescence
Molecular Orbitals
Single-Stranded DNA
Biología y Biomedicina / Biología
Descripción
Sumario:Many fluorophores display interesting features that make them useful biological labels and dyes, particularly in Cell Biology and Cytogenetics. Changes in the absorption-emission spectra (ortho- and metachromasia) are accounted among them. Acridine orange (AO) is one of such fluorochromes with an exemplary orthochromatic vs. metachromatic emission, which depends on its concentration and binding mode to different cell substrates. Here, we revisit the differential AO fluorescence that occurs in selected biological materials, which allows the identification of single-stranded or double-stranded nucleic acids. Although known for a long time, the ultimate reason for this differential phenomenon has not been properly addressed. We propose a potential molecular mechanism that adequately accounts for the distinct AO emission when bound either to denatured or denatured-reassociated DNA. This mechanism, based on theoretical molecular modelling, implies a difference in the degree of overlap of excited state orbitals whenever AO molecules are interacting with bases from single- or double-stranded nucleic acids. In the first case, massive orbital overlapping leads to a metachromatic red AO emission. Otherwise, no excited-state orbital overlapping occurs, due to excessive distance between intercalated AO molecules, which manifests as orthochromatic green fluorescence. Our molecular modelling supports this interplay between orbital overlap/not overlap and metachromatic/orthochromatic fluorescence