Peripheral Groups of Dicationic Pyrazinoporphyrins Regulate Lipid Membrane Binding

Abstract

Photodynamic therapy (PDT) is a widely used technique for skin cancer treatment and antimicrobial therapy. An improvement in PDT efficiency requires not only an increase in quantum yield of photosensitizer (PS) molecules but also their applicability for biological systems. Recently, we demonstrated that the activity of porphyrin-based PSs in the lipid membrane environment depends on the nature of the cation in the macrocycle due to its interactions with the lipid phosphate moiety, as well as the orientation of the PS molecules inside the membrane. Here, we report the synthesis, membrane binding properties and photodynamic efficiency of novel dicationic free-base, Ni(II) and Zn(II) pyrazinoporphyrins with terminal tetraalkylammonium units (2H-1, Ni-1 and Zn-1), to show the possibility to enhance the membrane binding of PS molecules, regardless of the central cation. All of these substances adsorb at the lipid membrane, while free-base and Zn(II) porphyrins actively generate singlet oxygen (SO) in the membranes. Thus, this study reveals a new way to tune the PDT activity of PSs in biological membranes through designing the structure of the peripheral groups in the macrocyclic photosensitizer.

Antimicrobial activity of photosensitizers: arrangement in bacterial membrane matters

“…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.…”