The localization and photosensitization of modified chlorin photosensitizers in artificial membranes

Abstract

In this work we investigate the localization and photophysical properties of twelve synthetically derived chlorins in artificial membranes, with the goal of designing more effective photosensitizers for photodynamic therapy (PDT). The studied chlorins incorporate substituents of varying lipophilicity at the C₅-meso-position (H to C₅H₁₁), while the C₁₃- and C₁₇-positions have carboxylate “anchoring” groups tethered to the tetrapyrrole by alkyl chains (CH₂)_n (n = 1–3). It was found that as n increases, the chromophoric part of the molecule, and thus the point of generation of singlet oxygen, is located at a deeper position in the bilayer. The vertical insertion of the sensitizers was assessed by two fluorescence-quenching techniques: by iodide ions that come from the aqueous phase and by spin-probe-labeled phospholipids that are incorporated into the bilayer, using the parallax method. These results demonstrate that elongation of the side chains endows the modified molecules with a larger affinity for artificial membranes and also causes the tetrapyrrole ring to be localized deeper in the lipid membrane. This location leads to a higher effective quantum yield for the chemical reaction of singlet oxygen with its chemical target 9,10-dimethylanthracene (DMA).