Synthesis of decacationic [60]fullerene decaiodides giving photoinduced production of superoxide radicals and effective PDT-mediation on antimicrobial photoinactivation

• Published in: European journal of medicinal chemistry Vol. 63; pp. 170 - 184
• Main Authors: Wang, Min, Maragani, Satyanarayana, Huang, Liyi, Jeon, Seaho, Canteenwala, Taizoon, Hamblin, Michael R., Chiang, Long Y.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-05-2013
• Subjects: Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Antimicrobial photodynamic therapy; Decacationic C60 monoadducts; Di(N,N′,N,N,N,N-hexapropyl-hexa(aminoethyl)amido)malonate arm; Escherichia coli - drug effects; Escherichia coli - radiation effects; Fullerenes - chemistry; Iodides - chemistry; Light; Microbial Viability - drug effects; Microbial Viability - radiation effects; Models, Chemical; Molecular Structure; Photochemotherapy - methods; Photoinduced radicals; Photosensitizer; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Spectrometry, Fluorescence; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectroscopy, Fourier Transform Infrared; Staphylococcus aureus - drug effects; Staphylococcus aureus - radiation effects; Superoxides - chemistry; Superoxides - metabolism; Transesterification; Photoinduced radicals; Transesterification; Decacationic C60 monoadducts; Di(N,N′,N,N,N,N-hexapropyl-hexa(aminoethyl)amido)malonate arm; Photosensitizer; Antimicrobial photodynamic therapy
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2013.01.052

We report a novel class of highly water-soluble decacationic methano[60]fullerene decaiodides C60[>M(C3N6+C3)2]–(I−)10 [1-(I−)10] capable of co-producing singlet oxygen (Type-II) and highly reactive hydroxyl radicals, formed from superoxide radicals in Type-I photosensitizing reactions, upon illumination at both UVA and white light wavelengths. The O2−·-production efficiency of 1-(I−)10 was confirmed by using an O2−·-reactive bis(2,4-dinitrobenzenesulfonyl)tetrafluorofluorescein probe and correlated to the photoinduced electron-transfer event going from iodide anions to 3C60*[>M(C3N6+C3)2] leading to C60−·[>M(C3N6+C3)2]. Incorporation of a defined number (ten) of quaternary ammonium cationic charges per C60 in 1 was aimed to enhance its ability to target pathogenic Gram-positive and Gram-negative bacterial cells. We used the well-characterized malonato[60]fullerene diester monoadduct C60[>M(t-Bu)2] as the starting fullerene derivative to provide a better synthetic route to C60[>M(C3N6+C3)2] via transesterification reaction under trifluoroacetic acid catalyzed conditions. These compounds may be used as effective photosensitizers and nano-PDT drugs for photoinactivation of pathogens.
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► Decacationic fullerenes were synthesized to co-produce Type-I and Type-II ROS. ► O2−·-production efficiency was confirmed by an O2−·-reactive probe. ► Use of ten positive charges enhanced its ability to target pathogenic bacterial cells. ► These compounds may be used as nano-PDT drugs for photoinactivation of pathogens.