Synthesis of decacationic C₇₀ bisadducts by incorporating covalently bound electron-donors for enhancement of radical-based type-I PDT

We designed, synthesized, and characterized two types of highly water-soluble C₇₀ monoadduct, C₇₀[>M(C ₃N₆⁺C₃)₂]-(I ^-)₁₀ (LC17), and bisadducts, C₇₀[>M(C ₃N₆⁺C₃)₂][>M(C ₃N₆C₃)₂] (LC18). Each of these compounds consist of a well-defined decacationic quaternary ammonium iodide moiety with ten positive charges per C₇₀ for increasing water-solubility and the ability to target pathogenic bacterial cells. The structural modification enables them to act as broad-spectrum antibacterial nano-PDT drugs. We found that white light was more effective with LC17 while UVA light was more effective with LC18 to the antimicrobial effects against human pathogens, Gram-positive (Staphylococcus aureus) and Gram-negative species (Escherichia coli and Acinetobacter baumannii). Both compounds were effective in a mouse model of Gram-negative 3^rd-degree burn infections. The observation led to our proposition that the attachment of an additional electron-donating deca(tertiary ethylenylamino)malonate arm to C₇₀, giving a product of LC18, allowed the moiety to act as a potent electron source and increased the generation yield of hydroxyl radicals under UVA illumination. This demonstrated a new approach in enhancing HO·-induced radical-killing (Type-I photochemistry) of pathogenic bacteria.