| Making use of various functionalizations of [60]fullerene, introducing solubilising groups or potentially biologically effective components to [60]fullerene to synthesize biologically compatible C60 derivatives, and investigating their biological activites have recently become a topic of importance in the fields of [60]fullerene chemistry and its biological applications. In this paper, amination reaction, photochemical reaction, and (Bingel)cycloaddition of C60, respectively, with amino-acids, iminodiacetic alkyl esters, azides, and malonates were carried out to prepare a few biologically compatible C60 derivatives. Their antioxidative and radical scavenging properties, and their protective effects on culturing cells were studied. The studies may provide basic data for finding better antioxidative C60 derivatives. Meanwhile, we also discussed and analyzed influencing factors of these biological properties and structure-activity relationships in order to obtain basic information for designing and synthesizing biologically compatible C60 derivatives.This paper has the following main aspects:1. Nucleophilic addition of C60 with amino-acids in toluene/ethanol gave the corresponding C60 amino-acid adducts (1a, 1b, 1c and 1d), their addition number (n) determined by elemental analysis: n=5 (1a), 5 (1b), 4 (1c) and 3 (1d). Addition number (n) of amination reaction of C60 was influenced by steric hindering of hydrocarbon chains of amino-acids and solubility of C60 adducts in reaction media.The experimentations of eliminating active oxygen radicals in chemical systems, mouse thymus cell cultures, and H2O2-induced erythrocytes oxidative hemolysis demonstrated that C60 amino-acid adducts (1a, 1b, 1c and 1d ) possess antioxidative and radical scavenging properties. With the increase of concentrations, their antioxidative and radical scavenging abilities increased.These experimentations also showed that antioxidative potencies of the C60 amino-acid adducts were with the same sequence: 1a > 1b ; 1a > 1c > 1dThe consistencies in the sequence reveal that steric hindering of addition groups of C60 amino-acid adducts and enhanced electron densities of the conjugated bonds of C60 core are intrinsic factors of influencing their antioxidative and radical scavenging abilities.2. The synthesis of fulleropyrrolidine carboxylic acid 2b and 3b were conveniently achieved in a 65% and 53%yield (relative to 2a and 3a), by a multiple-step process: photochemical reaction of C60 with iminodiacetic methyl ester (NH(CH2COOMe)2, further N-Alkylation, hydrolysis and acidification.2b and 3b, in the concentration range of 0 3×10-4 mol/L, have obvious scavenging activities against superoxide(O2-·)and hydroxyl (·OH) radicals generated in chemiluminescence systems. However, 2b and 3b were found to have no obvious differences in radical scavenging efficiency. The similar radical scavenging potencies can reasonably be ascribed to their identical [6,6]-closed structure of parent C60.Fulleropyrrolidine carboxylic acid 2b and 3b easily form aggregate in polar media. Critical aggregation concentrations (CAC) of their sodium salts were determined by conductivity measurements, which were 3.58×10-4 mol/L (2b) and 3.33×10-4 mol/L (3b). Their aggregation behaviors were further proved using UV-Vis absorption, static light scattering (SLS) and transmission electron microscopic (TEM) techniques. CAC and aggregate sizes of 2b and 3b were different from each other, indicating that the aggregate is effected by the number of carboxyl groups connected to fulleropyrrolidine mono-adduct derivatives.The experimentations of eliminating active oxygen radicals in chemical systems, and H2O2-induced erythrocytes oxidative hemolysis demonstrated that aggregation behavior of 2b or 3b resulted in the decline of their antioxidative and radical scavenging potencies. 3. C60-based ebselen derivatives 7 (53%) and 10 (42%, based on consumed C60 ) were synthesized.MTT assay and LDH leakage assay showed that 7 and 10 and their corresponding C60, ebselen derivatives can inhibit H2O2-induced neuronal injury, and C60-based ebselen derivatives (7, 10) possess stronger nuroprotective potencies than parent C60, or ebselen derivatives alone. NADPH-RD coupled enzymatic assay also showed that the GPX activities of 7, or 10 were higher than those of parent C60, or ebselen derivatives.The C60-based ebselen derivatives showed stronger nuroprotective potency than parent C60, or ebselen derivatives alone. This enhanced nuroprotective potencies can reasonably be attributed to both improvement of its free radical scavenging capabilities and improvement of GPX-like activities. Therefore, selecting appropriate antioxidant components and introducing them to [60]fullerenes, should be an effective methods of obtaining more biologically effective C60-based antioxidants.
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