Antimicrobial Photodynamic Therapy with Functionalized Fullerenes: Quantitative Structure-activity Relationships

Area of Science:

• Biochemistry
• Materials Science
• Microbiology

Background:

• Photodynamic therapy (PDT) utilizes photosensitizers (PS) with light and oxygen to generate reactive oxygen species for cell death.
• Antimicrobial PDT is an emerging infection treatment using microbial-selective PS.
• Common antimicrobial PS are based on tetrapyrrole or phenothiazinium structures with cationic or basic amino groups.

Purpose of the Study:

• To compare the antimicrobial efficacy of novel synthetic fullerene derivatives with basic or quaternary amino groups.
• To establish quantitative structure-function relationships for these fullerene-based PS.
• To evaluate their effectiveness against Gram-positive bacteria (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli), and fungi (Candida albicans).

Main Methods:

• Synthesis of fullerene derivatives with varying amino group substitutions (basic vs. quaternary).
• Assessment of antimicrobial activity using quantitative structure-function relationships, including LogP and hydrophilic-lipophilic balance.
• Testing against S. aureus, E. coli, and C. albicans under visible light irradiation.

Main Results:

• Fullerene derivatives with non-quaternary amino groups formed nanoaggregates and were only effective against S. aureus.
• Increased numbers of widely dispersed quaternary cationic groups on the fullerene cage enhanced antimicrobial effectiveness by minimizing aggregation.
• S. aureus showed the highest susceptibility, followed by E. coli, while C. albicans was the most resistant.

Conclusions:

• Quaternized fullerene derivatives are highly effective antimicrobial photosensitizers.
• The distribution and number of quaternary cationic groups are critical determinants of efficacy.
• These findings suggest potential applications for quaternized fullerenes in treating superficial microbial infections.