Synthesis of Decacationic C_(70) Bisadducts by Incorporating Covalently Bound Electron-Donors for Enhancement of Radical-based Type-Ⅰ PDT

摘要

We designed, synthesized, and characterized two types of highly water-soluble C_(70) monoadduct, C_(70)[＞M(C_3N_6~+C_3)_2]-(I~-)_(10) (LC17), and bisadducts, C_(70)[＞M(C_3N_6~+C_3)_2][＞M(C_3N_6C_3)_2] (LC18). Each of these compounds consist of a well-defined decacationic quaternary ammonium iodide moiety with ten positive charges per C_(70) 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 3rd-degree burn infections. The observation led to our proposition that the attachment of an additional electron-donating deca(tertiary ethylenylamino)malonate arm to C_(70), 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.