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

Author(s)

Vignoni, Alejandro ^[1] ; Layana, Carla ^[2] ; Junqueira, Helena C. ^[3] ; Thomas, Andres H. ^[4] ; Itri, Rosangela ^[5] ; Baptista, Mauricio S. ^[3] ; Vignoni, Mariana ^[4]

Affiliation

^[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

• Document type: Journal article
• Source: DYES AND PIGMENTS; v. 187, MAR 2021.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 19/12957-4 - Membrane photodamage by new lipophilic lumazine derivatives
• Grantee: Rosangela Itri
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• FAPESP's process: 16/04296-0 - Photosensitization and photodamage of cells and biomimetic models by pterin derivatives
• Grantee: Mauricio da Silva Baptista
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/50680-5 - Photosensitization in life sciences
• Grantee: Mauricio da Silva Baptista
• Support Opportunities: Research Projects - Thematic Grants