Medical Applications of Water-Soluble Polyhydroxylated Fullerene Derivatives
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Results exemplified the potential uses of functionalized fullerene derivatives in the biochemical or medical related applications. 7' 8
~ ~Oxidase
HN N
HN
•=
ON HH
0"
H
H
3
2
N®5
~
2NO3
Scheme 1 Water-soluble fullerenols 1 used in this study were synthesized by a sequence of reactions involving the electrophilic attack of nitronium tetrafluoroborate on fullerenes in the presence of organocarboxylic acids as a key-step of reaction. 9 Structurally, fullerenol 1 was found to consist of 18-20 hydroxy groups, on average, and several hemiketal moieties. 10 Aside from its desirable water solubility, conjugated diols and vic-diols in 1 are potentially good ligands for coordination or binding on enzyme surfaces. To evaluate and determine the potential influence of these diols on the enzymatic activity of xanthine oxidase, we carried out the fullerenol concentration dependent study of the uric acid production by xanthine oxidase. The conversion of xanthine 2 to uric acid 3 can be detected by the specific optical absorption of uric acid at 290 nm as shown in Scheme 1. Experimentally, the optical absorbance at the constant wavelength of 290 nm was measured on an aqueous solution suspended with a proper amount of xanthine and xanthine oxidase. Upon the addition of fullerenol, at various final concentration (from 10 to 50 jig/mi), into the aqueous solution, the relative optical intensity of uric acid was observed to remain nearly constant as shown in Figure 1. Results clearly indicated that fullerenols gave no enzymatic inhibition on xanthine oxidase. To monitor unstable trace amount of superoxide radicals in aqueous solution, a chemiluminescence technique was applied with lucigenin (bis-N-methylacridinium nitrate) 4 as a chemiluminigenic probe for enhancing the delectability of superoxide. In this method, biscationic lucigenin salt was first reduced electronically by enzyme to give the corresponding cation-radical of lucigenin. The subsequent reaction of lucigeninic cation radical with superoxide radical afforded N-methylacridone 5 in a electronically excited state, which relaxed
328
back to its ground state resulting the emission of a photon, as shown in Scheme 1. Therefore, the intensity of lucigenin-derived chemiluminescence can be correlated to the relative quantity of superoxide radical in solution. As a result, we observed systematic decrease in intensity of chemiluminescence upon the addition of fullerenols in increasing concentration as shown in Figure 2. The data clearly indicated the excellent efficiency of fullerenol in eliminating superoxide radical species generated by xanthine/xanthine oxidase. At an applied fullerenol concentration level of 50 jig/mi, a value of approximately 80% radical scavenging efficiency was obtained. 0.45-
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0.40
*
0.35
•_0.30 a
Xanthlne/Xanthine Oxidase in Aaueous Solution
0.25 E0.20 ca0.15 0.10 0.05
0.000
i
i
I
i
I
10
20
30
40
50
60
C60 final concentration (ug/mi)
Figure 1: The fullerenol concentration dependent of the optical absorbance of uric a
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