Alkylation converts riboflavin into an efficient photosensitizer of phospholipid membranes

A new decyl chain [−(CH2)9CH3] riboflavin conjugate has been synthesized and investigated. A nucleophilic substitution (SN2) reaction was used for coupling the alkyl chain to riboflavin (Rf), a model natural photosensitizer. As expected, the alkylated compound (decyl-Rf) is significantly more lipoph...

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Detalles Bibliográficos
Autores: Sosa, María José, Fonseca Castro, José Luis, Sakaya, Aya, Urrutia, María Noel, Petroselli, Gabriela, Erra Balsells, Rosa, Quindt, Matías Iván, Bonesi, Sergio Mauricio, Cosa, Gonzalo, Vignoni, Mariana, Thomas, Andrés Héctor
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/228454
Acceso en línea:http://hdl.handle.net/11336/228454
Access Level:acceso abierto
Palabra clave:GUVS
LIPID PEROXIDATION
LUVS
NUCLEOPHILIC SUBSTITUTION
RIBOFLAVIN
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
Descripción
Sumario:A new decyl chain [−(CH2)9CH3] riboflavin conjugate has been synthesized and investigated. A nucleophilic substitution (SN2) reaction was used for coupling the alkyl chain to riboflavin (Rf), a model natural photosensitizer. As expected, the alkylated compound (decyl-Rf) is significantly more lipophilic than its precursor and efficiently intercalates within phospholipid bilayers, increasing its fluorescence quantum yield. The oxidative damage to lipid membranes photoinduced by decyl-Rf was investigated in large and giant unilamellar vesicles (LUVs and GUVs, respectively) composed of different phospholipids. Using a fluorogenic probe, fast radical formation and singlet oxygen generation was demonstrated upon UVA irradiation in vesicles containing decyl-Rf. Photosensitized formation of conjugated dienes and hydroperoxides, and membrane leakage in LUVs rich in poly-unsaturated fatty acids were also investigated. The overall assessment of the results shows that decyl-Rf is a significantly more efficient photosensitizer of lipids than its unsubstituted precursor and that the association to lipid membranes is key to trigger phospholipid oxidation. Alkylation of hydrophilic photosensitizers as a simple and general synthetic tool to obtain efficient photosensitizers of biomembranes, with potential applications, is discussed.