Mechanisms of Singlet‐Oxygen and Superoxide‐Ion Generation by Porphyrins and Bacteriochlorins and their Implications in Photodynamic Therapy

Abstract

New halogenated and sulfonated bacteriochlorins and their analogous porphyrins are employed as photosensitizers of singlet oxygen and the superoxide ion. The mechanisms of energy and electron transfer are clarified and the rates are measured. The intermediacy of a charge-transfer (CT) complex is proved for bacteriochlorins, but excluded for porphyrins. The energies of the intermediates and the rates of their interconversions are measured, and are used to obtain the efficiencies of all the processes. The mechanism of formation of the hydroxyl radical in the presence of bacteriochlorins is proposed to involve a photocatalytic step. The usefulness of these photosensitizers in the photodynamic therapy (PDT) of cancer is assessed, and the following recommendations are given for the design of more effective PDT protocols employing such photosensitizers: 1) light doses should be given over a more extended period of time when the photosensitizers form CT complexes with molecular oxygen, and 2) Fe(2+) may improve the efficiency of such photosensitizers if co-located in the same cell organelle assisting with an in vivo Fenton reaction.

New Halogenated Water‐Soluble Chlorin and Bacteriochlorin as Photostable PDT Sensitizers: Synthesis, Spectroscopy, Photophysics, and in vitro Photosensitizing Efficacy

“…[44] The quenching rate constants measured for bacteriochlorins are faster, providing evidence for the presence of charge-transfer interactions, as detailed in the literature. [42] These values are consistent with diffusion limited energy transfer from the triplet state of the sensitizer to molecular oxygen. [54] Singlet oxygen quantum yields were obtained from phosphorescence at 1270 nm using the method described below.…”

“…The lower F D observed for the bacteriochlorin is precedented in related bacteriochlorins [38] and is attributed to the involvement of charge-transfer in the mechanism of energy transfer to molecular oxygen that may lead to the formation of the superoxide ion. [42] Spectroscopic evidence for electron transfer from electronically excited (5,10,15,20-tetrakis(2,6-dichloro-5-sulfophenyl)bacteriochlorin to molecular oxygen in dimethylsulfoxide, resulting in the formation of O 2 À C, was recently described using a spin trap. [42] Cytotoxicity assay…”

“…Type II photooxygenation processes seem to be favored over Type I processes in more effective PDT, but there are also claims of an amplified PDT response when superoxide is generated as well. [41,42] Moreover, cyclic tetrapyrroles appear to have an intrinsic ability to accumulate in tumors. [43] In addition to the desirable photophysical and biological properties mentioned above, the ideal photosensitizer must have reasonable solubility in aqueous media.…”

Photodynamic Action of Single-Walled Carbon Nanotubes

“…A few studies have suggested that it depends on the structure and concentration of the PS and the concentration of O 2 . [24][25][26] The effects of PDT on tumor tissues are now known to be due to four mechanisms: (1) direct cytotoxicity, (2) vascular injury, (3) inflammatory response, and (4) host immune response 27,28) (Fig. 5).…”

Tissue Uptake Study and Photodynamic Therapy of Melanoma‐Bearing Mice with a Nontoxic, Effective Chlorin

“…The enhanced phototoxicity of the bacteriochlorin was attributed, in part, to the generation superoxide ion (O 2 C À ) by electron transfer in competition with the generation of singlet oxygen ( 1 O 2 ) by energy transfer. [29] The higher phototoxicity of the bacteriochlorin motivated its choice for the first in vivo studies with this series of compounds. [25] The biodistribution of TCPBSO 3 H in DBA mice bearing S91 tumors revealed that the tumor-to-skin ratio increases with time, reaching approximately 10 in the first 48 h post-i.v.…”