On the mechanism of DNA cleavage by fullerenes investigated in model systems:: Electron transfer from guanosine and 8-oxo-guanosine derivatives to C60
On the mechanism of DNA cleavage by fullerenes investigated in model systems:: Electron transfer from guanosine and 8-oxo-guanosine derivatives to C60
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DOI：
10.1021/ja983335d
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发表时间：
1999-01-20
影响因子：
15
通讯作者：
Foote, CS
中科院分区：
文献类型：
--
作者：
Bernstein, R;Prat, F;Foote, CS
DNA选择性光切割是一个非常活跃的研究领域，已经报道了许多人工光核酸酶。1-3富勒烯和二氢富勒烯是贫电子光敏剂，由这些化合物介导的DNA光裂解（对G有选择性）已被几个小组报道。4-7有两种可能的机制，I型，涉及从G到富勒烯的电子转移，和II型，其中富勒烯产生的单线态氧（1 O2）是活性氧化剂（方案1）。富勒烯和二氢富勒烯的物理和电化学性质使得I型和II型途径都成为可能。C60的激发三重态的还原电位E0（3C 60/C60·-）为+ 1.14 V（相对于苄腈中的SCE），8而Guo在DMF中的还原电位E0（Guo·+/Guo）为+ 1.26 V。9因此，从Guo到3C 60可能发生轻微的吸能电子转移。C60也是一种优良的单线态氧敏化剂（φΔ）1），10，其三线态与氧反应迅速（kq）1.9× 109 M-1 s-1）。[11]在水和极性溶剂中，单线态氧被Guo猝灭，速率常数为106 × 106 M-1 s-1，但化学反应速率常数仅为101 × 105 M-1 s-1。9、12大多数作者都认为是第二类机制。然而，An等人的报告表明，至少在一种情况下，与带有二氢富勒烯敏化剂的互补链结合的寡核苷酸中G氧化的机制可能是I型。[5] DNA氧化的另外两个特征使情况进一步复杂化。首先，鸟苷堆比郭本身更容易氧化。[13]计算表明，B-DNA构象中的GG堆叠可以比孤立的Guo更容易氧化0.4 V（相当于9.2 kcal/mol），并且5′ G应该优先受到攻击。因此，含有GG堆叠的DNA链可能比没有这种特定排列的链更有利于I型氧化。
Selective DNA photocleavage is a very active field of research, and a number of artificial photonucleases have been reported. 1-3 Fullerenes and dihydrofullerenes are electron-poor photosensitizers, and DNA photocleavage (selective for G) mediated by these compounds has been reported by several groups. 4-7 Two mechanisms are possible, type I, involving electron transfer from G to fullerene, and type II, in which singlet oxygen (1O2) generated by the fullerene is the active oxidant (Scheme 1). The photophysical and electrochemical properties of fullerenes and dihydrofullerenes make both type I and type II pathways possible. The reduction potential of the excited triplet state of C60, E0 (3C60/C60•-), is+ 1.14 V vs SCE in benzonitrile, 8 whereas that of Guo in DMF, E0 (Guo•+/Guo), is+ 1.26 V. 9 Therefore, slightly endergonic electronic transfer could occur from Guo to 3C60. C60 is also an excellent singlet oxygen sensitizer (φΔ) 1), 10 and its triplet state reacts with oxygen rapidly (kq) 1.9× 109 M-1 s-1). 11 Singlet oxygen is quenched by Guo with a rate constant of∼ 6× 106 M-1 s-1 in water and polar solvents, but the chemical reaction rate constant is only∼ 1× 105 M-1 s-1. 9, 12 The type II mechanism has been assumed by a majority of authors. However, a report by An et al. showed that, in at least one case, the mechanism of G oxidation in an oligonucleotide bound to a complementary strand bearing a dihydrofullerene sensitizer was probably type I. 5Two additional features of DNA oxidation further complicate the situation. First, guanosine stacks are more prone to oxidation than Guo itself. 13 Calculations suggest that a GG stack in a B-DNA conformation can be as much as 0.4 V (equivalent to 9.2 kcal/mol) more easily oxidized than an isolated Guo, and that the 5′ G should be preferentially attacked. 14, 15 Therefore, DNA strands containing GG stacks might well favor type I oxidation over strands without this particular arrangement.