Tuning the Polarity of Fullerene C60 Derivatives for Enhanced Photodynamic Inactivation

• Published in: Photochemistry and photobiology Vol. 97; no. 6; pp. 1431 - 1444
• Main Authors: Palacios, Yohana B., Durantini, Javier E., Heredia, Daniel A., Martínez, Sol R., González de la Torre, Laura, Durantini, Andrés M.
• Format: Journal Article
• Language: English
• Published: Lawrence Blackwell Publishing Ltd 01.11.2021
• Subjects: Analogs; Biomimetics; Buckminsterfullerene; Charge distribution; Coliforms; Deactivation; E coli; Fluorescence; Fullerenes; Inactivation; Methicillin; NADH; Nicotinamide adenine dinucleotide; Photosensitization; Polarity; Reactive oxygen species; Reverse micelles; Singlet oxygen; Toluene; Tryptophan
• ISSN: 0031-8655; 1751-1097
• DOI: 10.1111/php.13465

In this article, four novel fulleropyrrolidines derivatives were synthesized to study how the effect of polarity and positive charge distribution can influence the efficacy of photodynamic inactivation treatments to kill bacteria. The design of the photosensitizers was based on DFT calculations that allowed us to estimate the dipolar moment of the molecules. Neutral compounds bearing N‐methyl bis‐acetoxy‐ethyl (1) and bis‐hydroxyethyl (2) amine were the starting material to obtain the dicationic analogs N,N‐dimethyl bis‐methoxyethyl (3), and bis‐acetoxy‐ethyl) (4) methylammonio. As expected from fullerene C60 derivatives, compounds 1‐4 absorb in the UV region, with a peak at 430 nm, a broader range of absorption up to 710 nm, and exhibit weak fluorescence emission in toluene and reverse micelles. In the biomimetic AOT micellar system, the highest singlet oxygen photosensitization was found for compounds 1, followed by 3, 2, and 4. Whereas 4 was the most effective reducing nitro blue tetrazolium in the presence of β‐NADH. The influence of type I and type II mechanism on the photodynamic activity of compounds 3 and 4 was further examined in the presence of L‐tryptophan and two reactive oxygen species scavengers. In vitro experiments indicated that the compounds with the highest dipolar moments, 3 (37.19 D) and 4 (38.46 D), inactivated methicillin‐resistant Staphylococcus aureus and Escherichia coli bacteria using an energy dose <2.4 J cm−2. No inactivation was observed for the neutral analogs with the lowest dipolar moments. These findings help to optimize sensitizer structures to improve photodynamic inactivation. In this work, the structures of dicationic fulleropyrrolidines derivatives were optimized using DFT calculations to attain high dipolar moments. Our endeavor was focused on studying how the effect of polarity (given by the dipolar moment of the molecules) and positive charge distribution can influence the efficacy of photodynamic inactivation treatments to kill bacteria. This work opens a new paradigm in the design of photosensitizers.