A novel tricationic fullerene C60 as broad-spectrum antimicrobial photosensitizer: mechanisms of action and potentiation with potassium iodide

MAXIMILIANO L. AGAZZI ; MARÍA GABRIELA ALVAREZ,; EZEQUIEL D. QUIROGA ; JAVIER E. DURANTINI ; EDGARDO N. DURANTINI

Photochemical and Photobiological Sciences

ROYAL SOC CHEMISTRY

Lugar: CAMBRIDGE; Año: 2021 vol. 20 p. 327 - 341

1474-905X

A novel photosensitizing agent based on a tricationic fullerene C60 (DMC603+) wasefficiently synthesized from its non-charged analogue MMC60. This fulleropyrrolidinecontains a methyl(piperazinylphenyl)pyrrolidine monoadduct, which was methylated toform DMC603+ in 95% yield. The incidence of a tricationic structure in the periphery ofDMC603+ considerably increases the dipole moment in comparison with MMC60.These fullerenes presented strong UV absorptions, with the characteristic peak at 430nm and a broad range of less intense absorption up to 710 nm. Both compoundsshowed low fluorescence emission and were able to photosensitize singlet molecularoxygen, O2(1Δg). Furthermore, the generation of superoxide anion radical mediated byMMC60 and DMC603+ was observed in presence of NADH. Photodecomposition of Ltryptophan sensitized by both fullerenes indicated an involvement of type II pathway insolution. The photodynamic inactivation sensitized by MMC60 and DMC603+ wasexamined on Staphylococcus aureus, Escherichia coli and Candida albicans. In allthree microorganisms, MMC60 showed considerably lower photoactivity than forDMC603+. A reduction of 5.5 logs (99.9996%) in the S. aureus viability was found with0.5 μM DMC603+ and 30 min irradiation. Also, phototoxicity of 3.6 logs (99.97) wasobserved when E. coli cells were treated with 1.0 μM photosensitizer. Also, a completephotokilling of C. albicans was reached with 2.5 μM DMC603+ and 15 min irradiation.Mechanistic insight of PDI mediated by DMC603+ indicated that the bacterialphotokilling was mediated by contributions of both type I and type II mechanisms. Incontrast, a greater preponderance of the type II pathway was found in C. albicans. Onthe other hand, PDI treatments sensitized by DMC603+ in presence of potassiumiodide allowed substantially increasing the antimicrobial effect due to the formation ofreactive iodine species, mainly triiodide anion. Therefore, the highly amphiphilicDMC603+ can be used as an effective potential broad-spectrum antimicrobialphotosensitizer