Lipid Membrane Adsorption Determines Photodynamic Efficiency of β-Imidazolyl-Substituted Porphyrins

Abstract

Photosensitizers (PSs) represent a group of molecules capable of generating reactive oxygen species (ROS), such as singlet oxygen (SO); thus, they are considered to be promising agents for anti-cancer therapy. The enhancement of the photodynamic efficiency of these compounds requires increasing the PS activity in the cancer cell milieu and exactly at the target cells. In the present work, we report the synthesis, lipid membrane binding and photodynamic activity of three novel cationic PSs based on β-imidazolyl-substituted porphyrin and its Zn(II) and In(III) complexes (1H2, 1Zn and 1In). Comparison of the behavior of the investigated porphyrins at the bilayer lipid membrane (BLM) demonstrated the highest adsorption for the 1In complex and the lowest one for 1Zn. The photodynamic efficiency of these porphyrins was evaluated by determining the oxidation rate of the styryl dye, di-4-ANEPPS, incorporated into the lipid membrane. These rates were proportional to the surface density (SD) of the porphyrin molecules at the BLM and were roughly the same for all three porphyrins. This indicates that the adsorption of these porphyrins at the BLM determines their photodynamic efficiency rather than the extinction or quantum yield of singlet oxygen.

Antimicrobial activity of photosensitizers: arrangement in bacterial membrane matters

“…The experimental setup was as described by us earlier ( Sokolov and Pohl, 2009 ; Jiménez-Munguía et al, 2019 ). In brief, bilayer lipid membranes (BLMs) were formed by the Mueller-Rudin technique ( Mueller et al, 1963 ) from a 15 mg/mL solution of 1,2-diphytanoyl- sn -glycero-3-phospholcholine, DPhPC (Avanti Polar Lipids, Alabaster, AL, United States), in n -decane (Sigma-Aldrich, Saint-Louis, MO, United States) at an aperture (diameter of 0.8 mm) in a septum dividing two compartments (2 mL each) of a Teflon cell.…”

“…We have shown recently that the photodynamic efficacy of both substituted porphyrins and phthalocyanines depends on their ability to bind to lipid membranes ( Sokolov et al, 2018 ; Jiménez-Munguía et al, 2019 ). We have suggested a model describing the effect of PS location in the membrane on its ability to generate singlet oxygen.…”

“…We have suggested a model describing the effect of PS location in the membrane on its ability to generate singlet oxygen. The approach we have utilized to study the binding of PS to biological membranes is in vitro modeling of photodynamic processes using model bilayer lipid membranes (BLM) ( Konstantinova et al, 2018 ; Sokolov et al, 2018 ; Jiménez-Munguía et al, 2019 ; Polivanovskaia et al, 2022 ). Simultaneously, we have demonstrated that cationic phosphorus(V) porphyrins possess remarkable photophysical properties including efficient generation of singlet oxygen in water that can be tuned by the varying nature of axial ligands ( Meshkov et al, 2017 ).…”

Noncovalent interactions in gold(iii) tetrakis(4-butoxyphenyl)porphyrinate structures

“…16 In turn, it allows tuning of the physicalchemical properties of the obtained compounds in a range from their solubility in organic or aqueous medium to the enhancement of photophysical outcome. 15,[17][18][19] Formation of metal complexes is an additional degree of freedom in the modification of the electronic structure of porphyrins and thus their characteristics. The presence of a metal center may drastically alter their photophysical, e.g.…”

Functionalized heterocycle-appended porphyrins: catalysis matters

“…In the framework of our ongoing projects, our investigations are focused on tetrapyrrolic compounds, namely porphyrins and phthalocyanines, and their synthetic modications and search for new types of applications. 17,[23][24][25][26][27][28][29][30][31][32][33] Recently, we developed synthetic strategies towards imidazole-and pyrazine-annulated porphyrins starting from tetrapyrrole dioxo-or diamino-derivatives and aromatic aldehydes. 28,[34][35][36][37][38] The sterically hindered tetrapyrrole was used as a synthetic platform for the development of bifunctionalized linear and angular annulated polyaromatic compounds, water soluble derivatives for biomimetic applications and macrocycles with terminal anchoring groups.…”