Photodynamic Therapy with Hexa(sulfo-n-butyl)[60]Fullerene Against Sarcoma In Vitro and In Vivo.

The hydrophilic molecular micellar hexa(sulfo-n-butyl)[60]fullerene (FC4S), first synthesized in 1998 as a photosensitizer (PS) has been reported to exhibit high efficacy for singlet oxygen generation and antimicrobial photodynamic inactivation. The purpose of this study was to investigate the effects of photoactivated FC4S for free radical generation and to mediate photodynamic therapy (PDT) of cancer in vitro and in vivo. The results demonstrated that following light irradiation, FC4S produced singlet oxygen, but after addition of electron donors such as ferrocytochrome c or NADH, FC4S also produced superoxide. The combination of FC4S with light irradiation was able to induce cytotoxicity to human fibrosarcoma cells and murine sarcoma 180 cells in vitro. Cell-killing was proportional to fluence as well as FC4S concentration. Photoirradiation by argon-ion laser after intraperitoneal injection of FC4S also resulted in inhibition of S180 tumor growth in vivo (up to 80% reduction of tumor volume). Hematological and blood biochemistry parameters of the cancer-bearing mice were improved by PDT. Based on these findings, we conclude that FC4S has a great potential as a nanomedicine in PDT for cancer.

Synthesis and photoluminescent properties of geometrically hindered cis-tris(diphenylaminofluorene) as precursors to light-emitting devices.

A novel highly luminescent tris-fluorenyl ring-interconnected chromophore tris(DPAF-C9) was synthesized using a C3 symmetrical triaminobenzene core as the synthon. This structure bears three light-harvesting 2-diphenylamino-9,9-dialkylfluorenyl (DPAF) ring moieties with each attached by two branched 3',5',5'-trimethylhexyl (C9) arms. A major stereoisomer was chromatographically isolated and characterized to possess a 3D structural configuration of cis-conformer in a cup-form. Molecular calculation at B3LYP/6-31G* level revealed the unexpected stability of this cis-cup-conformer of tris(DPAF-C9) better than that of the stereoisomer in a propeller-form and the trans-conformer. The structural geometry is proposed to be capable of minimizing the aggregation related self-quenching effect in the condensed phase. Fluorescence emission wavelength of tris(DPAF-C9) was found to be in a close range to that of PVK that led to its potential uses as the secondary blue hole-transporting material for enhancing the device property toward the modulation of PLED performance.

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

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 (3)C60*[>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.

Synthesis and characterization of highly photoresponsive fullerenyl dyads with a close chromophore antenna-C(60) contact and effective photodynamic potential.

We report the synthesis of a new class of photoresponsive C(60)-DCE-diphenylaminofluorene nanostructures and their intramolecular photoinduced energy and electron transfer phenomena. Structural modification was made by chemical conversion of the keto group in C(60)(>DPAF-C(n)) to a stronger electron-withdrawing 1,1-dicyanoethylenyl (DCE) unit leading to C(60)(>CPAF-C(n)) with an increased electronic polarization of the molecule. The modification also led to a large bathochromic shift of the major band in visible spectrum giving measureable absorption up to 600 nm and extended the photoresponsive capability of C(60)-DCE-DPAF nanostructures to longer red wavelengths than C(60)(>DPAF-C(n)). Accordingly, C(60)(>CPAF-C(n)) may allow 2γ-PDT using a light wavelength of 1000-1200 nm for enhanced tissue penetration depth. Production efficiency of singlet oxygen by closely related C(60)(>DPAF-C(2) (M)) was found to be comparable with that of tetraphenylporphyrin photosensitizer. Remarkably, the (1)O(2) quantum yield of C(60)(>CPAF-C(2) (M)) was found to be nearly 6-fold higher than that of C(60)(>DPAF-C(2) (M)), demonstrating the large light-harvesting enhancement of the CPAF-C(2) (M) moiety and leading to more efficient triplet state generation of the C(60)> cage moiety. This led to highly effective killing of HeLa cells by C(60)(>CPAF-C(2) (M)) via photodynamic therapy (200 J cm(-2) white light). We interpret the phenomena in terms of the contributions by the extended π-conjugation and stronger electron-withdrawing capability associated with the 1,1-dicyanoethylenyl group compared to that of the keto group.

Synthesis of covalently attached hexadecaanilines on carbon nanotubes: toward electronic nanocarbon preparation.

We describe the direct covalent-grafting synthesis of well-defined aniline oligomers, such as tetraaniline (A(4)) and hexadecaaniline (A(16), major)/eicosaaniline (A(20), minor), on the sidewalls of carbon nanotubes (CNTs), via dediazonization reaction, for achieving highly soluble nanomaterials suitable for printing purposes, with long-term physical stability. Chemically grafting a layer of electroactive hexadecaanilines on CNTs resembles semiconductive encapsulation of functionalized CNTs. The resulting covalent nanoconjugates SWNT-(A(4))(x), MWNT-(A(4))(x), SWNT-(A(16/20))(x), and MWNT-(A(16/20))(x) were characterized by various spectroscopic and microscopic mapping methods. The combination of transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) analyses provided direct evidence for A(16/20) attachment to the CNTs, giving confirmation of the presence of heteroatoms surrounding the CNTs that was absent in the parent CNTs. Subsequent atom mapping in the vicinity of the tube structure allowed us to illustrate the 3D distribution of heteroatoms along the CNT surface.

Synthesis and characterization of monolayers and Langmuir-Blodgett films of an amphiphilic oligo(ethylene glycol)-C60-hexadecaaniline conjugate.

A novel amphiphilic oligo(ethylene glycol)-C60-hexadecaaniline (A16) tricomponent conjugate, C60>(A16-EG43), possessing a well-defined number of repeating aniline donor units and a hydrophilic ethylene glycol oligomer chain was synthesized. The compound is composed of a covalently bound donor-acceptor chromophore structure. Molecular self-assembly of C60>(A16-EG43) at the air-water interface formed a densely packed Langmuir monolayer with all highly hydrophobic fullerene cages located above the liquid interface. The monolayer can then be transferred onto a glass substrate via Langmuir-Blodgett (LB) deposition. LB multilayered thin films formed by multiple deposition of the monolayer yielded broadened optical absorption peaks extending beyond 600 nm into the 950 nm region, suggesting strong intermolecular interactions among the C60 cages and the A16 moieties. An X-ray reflectometry study clearly reveals that the Langmuir film at the air-water interface consists of a C60 top layer and a bottom layer containing hexcadecaaniline and oligo(ethylene glycol) with gradually decreasing electron density over a distance of approximately 130 A above bulk water. The pressure isotherm shows that the packing density of the C60>(A16-EG43) monolayer, corresponding to a molecular area of approximately 95 A2/molecule, is similar to that of the surface area of the C60 monolayer. This result suggests that C60 packing plays a dominant role in guiding the formation of the monolayer structure. Further photoexcitation of hexadecaaniline moieties of aligned (C60>)-A16 layers by a flash light source induces cross linking between adjacent A16 segments forming an interlinked A16 array. Our results have demonstrated a unique fabrication method for preparing the aligned donor-acceptor array using strong intermolecular interactions between fullerenes as the molecular orientation guiding force in the Langmuir-Blodgett technique.

Self-assembled photoresponsive amphiphilic diphenylaminofluorene-C60 conjugate vesicles in aqueous solution.

Water-soluble oligo(ethylene glycolated) derivatives of two-photon absorptive diphenylaminofluorenocarbonyl-methano[60]fullerene, denoted as C60(>DPAF-EG6), were synthesized with their molecular self-assembly characteristics in H2O studied. The formation of nano- to submicron-sized spherical hollow vesicles with a shell width of 15-20 nm was observed by transmission electron microscopy (TEM) micrographs. This shell width fits approximately with the length of a disordered bilayer-like molecular packing of C60(>DPAF-EG6), arising from strong intermolecular hydrophobic interactions of fullerene cages. Photoinduced intramolecular charge separation followed by charge recombination on the nanosecond time scale, from the DPAF moiety to the C60 cage in the vesicle structure, was detected via transient spectroscopic measurements.

Intense near-infrared optical absorbing emerald green [60]fullerenes.

Synthesis of emerald green fullerenes (EF) C60[C(CH3)(CO2Et)2]6 and C60[C(CH3)(CO2-t-Bu)2]6 was performed by using hexaanionic C60 intermediate (C60-6) as a reagent in one-pot reaction for attaching six alkyl ester addends on one C60 cage. These EF compounds exhibit intense optical absorption over 600-940 nm, the longest optical absorption of the C60 cage among many [60]fullerene derivatives synthesized.

Synthesis of C60-diphenylaminofluorene dyad with large 2PA cross-sections and efficient intramolecular two-photon energy transfer.

The first, highly two-photon active C60 derivative comprised of a A-sp3-D conjugate structure was synthesized showing effective two-photon absorption cross-sections (sigma 2' = 196 x 10(-48) cm4 sec-1 molecule-1) in the nanosecond regime among the best values for diphenylaminofluorene-based AFX chromophores.