Photo-induced cytotoxicity of malonic acid [C60] fullerene derivatives and its mechanism X. L. Yang*, C. H. Fan, H. S. Zhu Research Center of Materials Science, Beijing Institute of Technology, PO Box 327, Beijing 100081, PR China Accepted 10 August 2001 The biological activities of fullerenes have attracted extensive attention in recent years. The aim of this paper is to study the relation of the photo-induced cytotoxicity of fullerene derivatives to their chemical structures as well as the possible cellular mechanism involved in the photocytotoxicity. Three C60 derivatives with two to four malonic acid groups (DMA C60, TMA C60 and QMA C60) were prepared and the cytotoxicity of these compounds against HeLa cells was determined by MTT. Cell cycle was measured by flow cytometry. The results showed that the cytotoxicity of the malonic acid C60 derivatives was irradiation-and dosedependent. The sequence of their photo-induced growth inhibition was DMA C60>TMA C60>QMA C60. Hydroxyl radical quencher mannitol (10mm) was not able to prevent cells from the damage induced by irradiated DMA C60. DMA C60,together with irradiation,was found to have an ability of inducing a decrease in the number of G1 cells from 63 to 42% and a rise in that of G2+M cells from 6 to 26%. These data indicated that the number of malonic acid molecules added to C60 played an important role in the phototoxicity and the blockage of cell cycle might be a mechanism of this activity.

在Mn(OAc)3•2H2O 催化下, C60分别和亚甲基二膦酸四乙酯、氰基亚甲基膦酸二乙酯或乙氧羰基亚甲基膦酸二乙酯在氯苯中回流, 生成3个单加成环丙烷富勒烯膦酸衍生物C60C(R)PO(OEt)2 [1, R＝PO(OEt)2; 2, R＝COOEt; 3, R＝CN]. 与以前报道的Bingel反应法相比, 该方法副产物少并且缩短了反应时间. 采用循环伏安法发现1, 2的还原电位相对于C60发生负移, 而3的还原电位相对于C60却正移40 mV, 表明引入象氰基一样具有很强吸电子能力的取代基团, 可以改善富勒烯球的电化学性能, 合成电子接受能力较强的富勒烯衍生物.

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The biological activities of fullerene derivatives have attracted much attention in the last decade. In this paper, effects of dimalonic acid C60 (DMA C60) on cytoplasmic membrane, intracellular calcium concentration ([Ca2+]i), and mitochondrial membrane in HeLa cells were studied by using laser scanning confocal microscopy together with fluorescent probes propidium iodide (PI), fluo-3 acetoxymethyl ester (fluo-3 AM), and tetramethyl rhodamine methyl ester (TMRM). The data showed that under laser irradiation produced by a Kr/Ar laser source with a low power less than 1 mW, DMA C60 might induce damages against both cytoplasmic and mitochondrial membranes in a time- and dose-dependent manner. Prior to leakage of cytoplasmic membrane, a transient increase in [Ca2+]i occurred due to influx of calcium from the culture medium. These data provided some novel clues to explain the mechanisms involved in the photo-induced cytotoxicity of fullerene derivatives.

Synthesis of novel methanophosphonate and methanophosphonic acid C60 derivatives was achieved, and their cytotoxicity was studied. In particular, a bis-methanophosphonate C60 derivative displayed photo-induced cytotoxicity on HeLa cells with IC50 value of 1.30