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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Alkylation of a hydrophilic photosensitizer enhances the contact-dependent photo-induced oxidation of phospholipid membranes

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Autor(es):
Vignoni, Alejandro [1] ; Layana, Carla [2] ; Junqueira, Helena C. [3] ; Thomas, Andres H. [4] ; Itri, Rosangela [5] ; Baptista, Mauricio S. [3] ; Vignoni, Mariana [4]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Politecn Valencia, IU Automat & Informat Ind Ai2, Synthet Biol & Biosyst Control Lab, Cami Vera S-N, Valencia 46022 - Spain
[2] Univ Nacl La Plata, Fac Cs Exactas, Ctr Reg Estudios Genom, Blvd 120 Nr 1459, RA-1900 La Plata - Argentina
[3] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo - Brazil
[4] Univ Nacl La Plata, CCT La Plata CONICET, Dep Quim, Inst Invest Fisicoquim Teor & Aplicadas, RA-1900 La Plata - Argentina
[5] Univ Sao Paulo, Inst Fis, Dept Fis Aplicada, BR-05508090 Sao Paulo - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: DYES AND PIGMENTS; v. 187, MAR 2021.
Citações Web of Science: 0
Resumo

Lipophilic photosensitizers able to photo-induce lipid oxidation in biomembranes are, in general, much more efficient than hydrophilic ones; acting through the formation of singlet oxygen (O-1(2)), which oxidizes the fatty acid double bonds (type II mechanism). Here we investigate the binding and photosensitizing properties of 4-(decyloxy)pteridin-2-amine (O-decyl-Ptr) using unilamellar vesicles of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), a phospholipid with monounsaturated fatty acids. By means of molecular dynamic (MD) simulations, we showed that O-decyl-Ptr binds to the membrane in a localization that favors the direct reaction of the triplet excited state of O-decyl-Ptr with DOPC double bonds. As a consequence, although O-1(2) is formed, O-decyl-Ptr acts mainly as a contact-dependent photosensitizer, meaning through radical formation (type I mechanism). Mass spectrometry analysis of vesicles irradiated in the presence of O-decyl-Ptr, demonstrated the generation of alcohols (LOH), ketones (LO) and hydroperoxides (LOOH). In agreement with the mechanistic hypothesis proposed, LOH and LO (type I photooxidation products) are formed faster than LOOH (type II photooxidation product). Interestingly, no short-chain oxidized products were detected. Accordingly, membrane fluctuations and formation of filaments and buds are observed during in-situ photo-activation of O-decyl-Ptr in giant unilamellar vesicles due to changes in membrane spontaneous curvature. Finally, we evaluated the effect of the photochemical processes studied at a cellular level and demonstrated in experiments of viability of mammalian cells that O-decyl-Ptr has important photodynamic properties. Similar experiments performed using the hydrophilic photosenstizer pterin (Ptr) show that alkylation leads to a striking increase in the efficiency of photosensitized lipid oxidation. (AU)

Processo FAPESP: 19/12957-4 - Fotodano em biomembranas por derivados lipofílicos de lumazine
Beneficiário:Rosangela Itri
Modalidade de apoio: Auxílio à Pesquisa - Pesquisador Visitante - Internacional
Processo FAPESP: 16/04296-0 - Fotossensibilização e fotodano de células e modelos biomiméticos por derivados pterin
Beneficiário:Mauricio da Silva Baptista
Modalidade de apoio: Auxílio à Pesquisa - Pesquisador Visitante - Internacional
Processo FAPESP: 13/07937-8 - Redoxoma
Beneficiário:Ohara Augusto
Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 12/50680-5 - Fotossensibilização nas ciências da vida
Beneficiário:Mauricio da Silva Baptista
Modalidade de apoio: Auxílio à Pesquisa - Temático