Catechol amide derivatized polyhydroxylated fullerene as potential chelating agents of radionuclides: Synthesis, reactive oxygen species scavenging, and cytotoxic studies.

Radionuclide internal contamination can induce chemical and radioactive intoxication and produce harmful free radicals in vivo. At present, administration of chelating agents is the most effective treatment against nuclide contamination. However, traditional studies on chelating agents have ignored the damage caused by free radicals to the body. The present study aimed to develop a type of a bifunctional sequestering agent that can chelates nuclides and scavenges free radicals simultaneously. Therefore, a novel catechol amide-derivatized polyhydroxylated fullerene was designed and prepared. The poor water solubility of fullerene was ameliorated by chemically modifying hydrophilic catechol amide and multiple hydroxyl groups, and obtaining high water-soluble fullerene derivatives. The affinities of chelators were investigated via sulfochlorophenol competitive complexing method and antioxidant capacities were examined by electron paramagnetic resonance. The results revealed the good complexation of the designed and synthesized chelating agent with uranyl ions; and its efficiency in scavenging hydroxyl radicals. This chelating agent showed extremely low toxicity and notable protective effect against oxidative stress on A549 cells. Besides, in U(VI)-exposed A549 cells, immediate treatment with catechol amide-derivatized polyhydroxylated fullerene significantly decreased the lactate dehydrogenase (LDH) release by inhibiting the cellular U(VI) intake, promoting the intracellular U(VI) release and inhibiting the production of intracellular reactive oxygen species (ROS). These results suggest that this fullerene derivative may be a valuable in vivo antioxidant and radionuclide decorporation agent.

Synthesis and self-sensitized photo-oxidation of 2-fulleropyrrolines by palladium(ii)-catalyzed heteroannulation of [60]fullerene with benzoyl hydrazone esters.

A convenient and efficient Pd(OAc)2-catalyzed N-heteroannulation reaction of [60]fullerene with benzoyl hydrazone esters was exploited to synthesize novel and scarce N-unsubstituted 2-fulleropyrrolines via the formation of C-C and C-N bonds. Besides, the self-sensitized photo-oxidation of 2-fulleropyrrolines was first discovered under very mild conditions to yield a ketoamide fullerene derivative in high yields. The reaction kinetics of this self-sensitized photo-oxidation has been explored, indicating that this photo-oxidation process is a first-order reaction possessing a low reaction activation energy (2.79 kJ mol-1). Moreover, a possible mechanism related to the observed products was proposed.

Palladium-Catalyzed Reaction of [60]Fullerene with Aroyl Compounds via Enolate-Mediated sp2 C-H Bond Activation and Hydroxylation.

A convenient and highly efficient palladium-catalyzed reaction of [60]fullerene (C60) with aroyl compounds via enolate-mediated C-H activation and hydroxylation has been exploited for the first time to synthesize novel C60-fused dihydrofurans, and rare 1,4-fullerenols. Further functionalization including etherification, and esterification of synthesized 1,4-fullerenols provided efficient access to versatile fullerene derivatives. Moreover, a plausible reaction mechanism leading to the observed products is proposed.

Facile access to novel [60]fullerenyl diethers and [60]fullerene-sugar conjugates via annulation of diol moieties.

A general and facile annulation of various diol motifs to [60]fullerene has been developed. This protocol can afford not only 6- to 10-membered-ring fullerenyl diethers in one step from simple acyclic diols but also directly couple [60]fullerene with a variety of structurally diverse sugars. The [60]fullerene-sugar conjugates formed do not require any linker moiety and maintain their inherent structural integrity. The electrochemistry of the fullerenyl diethers and [60]fullerene-sugar conjugates has also been investigated.

An isomer of C60Cl10 free of skew-pentagonal-pyramidal C60Cl6 substructure.

Chlorination is an effective approach for understanding the feature of multiple additions on fullerene cages. The chlorofullerenes obtained are versatile synthons for further derivatization. However, chlorofullerenes used for chemical reaction studies are mainly based on the skew-pentagonal-pyramidal (SPP) C60Cl6. In this work, a new isomer of C60Cl10 that does not contain an SPP-C60Cl6 substructure was identified. Its electrochemical properties give it unexpected cyclic voltammetric behavior at more negative potentials relative to other chlorofullerenes. Friedel-Crafts arylation shows good reactivity of this compound. These new findings challenge opinions of fullerene addition patterns and will break the monopoly of C60Cl6 as a precursor for fullerene modifications.

Synthesis of [60]fullerene-fused tetrahydrobenzooxepine and isochroman derivatives via hydroxyl-directed C-H activation/C-O cyclization.

The palladium-catalyzed hydroxyl-directed C-H activation/C-O cyclization reaction of [60]fullerene with 2-phenylethyl alcohols and benzyl alcohols afforded [60]fullerene-fused tetrahydrobenzooxepine and isochroman derivatives in up to 43% yield. A plausible reaction mechanism is proposed, and the electrochemistry was also investigated.

Ab initio molecular dynamics simulation on the formation process of He@C60 synthesized by explosion.

The applications of endohedral non-metallic fullerenes are limited by their low production rate. Recently, an explosive method developed in our group shows promise to prepare He@C60 at fairly high yield, but the mechanism of He inserting into C60 cage at explosive conditions was not clear. Here, ab initio molecular dynamics analysis has been used to simulate the collision between C60 molecules at high-temperature and high-pressure induced by explosion. The results show that defects formed on the fullerene cage by collidsion can effectively decrease the reaction barrier for the insertion of He into C60, and the self-healing capability of the defects was also observed.

Study on the thermal reactions of [60]fullerene with amino acids and amino acid esters.

Thermal reactions of [60]fullerene with a series of amino acids and amino acid esters under aerobic and dark conditions have been investigated. Fulleropyrrolidines can be obtained from these reactions although an aldehyde is not added purposely. Possible reaction mechanisms involving uncommon C-N bond cleavages have been proposed to generate aldehydes, which then react with amino acids and amino acid esters to provide azomethine ylides, followed by 1,3-dipolar cycloaddition to [60]fullerene affording fulleropyrrolidines. Control experiments support our proposed mechanisms, and elucidate the innate nature of C-N bond cleavages of amino acids and amino acid esters.

Solvent-free reactions of C60 with active methylene compounds, either with or without carbon tetrabromide, in the presence of bases under high-speed vibration milling conditions.

Solvent-free reactions of C(60) with active methylene compounds, either with or without carbon tetrabromide (CBr(4)), in the presence of a base under high-speed vibration milling (HSVM) conditions were investigated. The reaction of C(60) with diethyl bromomalonate was conducted under HSVM conditions in the presence of piperidine, triethylamine or Na(2)CO(3) to afford cyclopropane derivative. In the presence of CBr(4), methanofullerenes, and could be obtained by the direct reaction of C(60) with diethyl malonate, dimethyl malonate, ethyl acetoacetate and ethyl cyanoacetate, respectively, with the aid of 1,8-diazabicyclo[5,4,0]undec-7-ene, piperidine, triethylamine or Na(2)CO(3). More interestingly, 1,4-bisadducts and were produced by the reaction of C(60) with diethyl malonate and dimethyl malonate in the presence of piperidine, triethylamine or Na(2)CO(3) under HSVM conditions. On the other hand, dihydrofuran-fused C(60) derivatives, and were obtained from the reaction of C(60) with ethyl acetoacetate, 2,4-pentanedione and 5,5-dimethyl-1,3-cyclohexanedione with the aid of a base. Under the same conditions, less activated aryl methyl ketones such as 2-acetylpyridine, 2-acetylpyrazine and acetophenone provided monocarbonylated methanofullerene derivatives, and. Except for the Bingel reactions, all other reactions under the HSVM conditions are considered to proceed according to a single-electron-transfer mechanism.