PHOTOINDUCED MEMBRANE DAMAGE BY AN EFFICIENT LIPOPHILIC RIBOFLAVIN DERIVATIVE

SOSA, MARÍA JOSÉ; FONSECA, JOSÉ LUIS; SAKAYA, AYA; URRUTIA, MARÍA NOEL; GABRIELA PETROSELLI; ROSA ERRA-BALSELLS; QUINDT, MATÍAS I.; BONESI, SERGIO M.; COSA, GONZALO; ANDRÉS H. THOMAS; MARIANA VIGNONI

Maresias

Conferencia; XV ELAFOT; 2023

Lipid peroxidation can occur in many physiological and pathological processes [1,2] and it may be triggered by electromagnetic radiation (photosensitized reactions), promoting damage in the photosynthetic system, food oxidation and skin photodamage. However, lipid photo-oxidation can be advantageously induced in important applications such as disinfection and photodynamic therapy (PDT) [3,4]. It has been suggested that the interaction of some lipophilic photosensitizers with biomembranes explains their high photodamaging capabilities [5], since the process is not limited by diffusion. On this matter, we have been working on the conversion of water-soluble heterocyclic compounds into highly lipophilic versions via introduction of an alkyl chain [6,7]. In this work, a new decyl chain riboflavin conjugate has been synthesized by a nucleophilic substitution (SN2) reaction. 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 unilamellar vesicles. 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 was 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.[1] Girotti, A. W. J. Lipid Res. 39:1529 (1998).[2] Reis, A. Free Rad. Biol. Med. 111:25 (2017).[3] Girotti, A. W. J Photochem Photobiol B 63:103 (2001).[4] Valenzeno, D. P. Photochem. Photobiol. 46:147 (1987).[5] Bacellar, I, et. al. JACS, 140:9606 (2018).[6] Vignoni, M., et. al. Mol. Pharma. 15:798 (2018).[7] Sosa, M. J., et. al. Photochem. Photobiol. 97:80 (2021)