Quantum Chemical Study of the Electron-Transfer-Catalyzed Splitting of Oxetane and Azetidine Intermediates Proposed in the Photoenzymatic Repair of (6-4) Photoproducts of DNA
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- 作者：Yinsheng Wang ; Peter P. Gaspar ; and John-Stephen Taylor
- 刊名：Journal of the American Chemical Society
- 出版年：2000
- 出版时间：June 14, 2000
- 年：2000
- 卷：122
- 期：23
- 页码：5510 - 5519
- 全文大小：226K
- 年卷期：v.122,no.23(June 14, 2000)
- ISSN：1520-5126
文摘
Semiempirical AM1 and PM3 calculations were used to study the electron-transfer-catalyzed splittingof oxetanes and azetidines that have been proposed as intermediates in the photoenzymatic repair of the (6-4)photoproducts of dipyrimidine sites in DNA by (6-4) photolyase. The calculations show that the gas-phasesplitting of an anion radical to a product complex is more exothermic than that of a cation radical, and thatboth are more exothermic than the neutral pathway. Low-energy pathways for splitting were found to occurby nonconcerted, two-step mechanisms for both anion and cation radical pathways, but only the anion radicalshad lower rate-determining barriers for splitting than did the neutral species. In the anion radical pathway,which is thought to be followed by the enzymatic reaction, cleavage of the C5-O4' or C5-N4' bond followedby cleavage of the C6-C4' bond is more favorable kinetically than cleavage in the reverse order. Though thebarrier for cleaving the C5-N4' bond first is significantly higher for the radical anion of the azetidine than thatfor cleaving the C5-O4' bond of the oxetane, protonation of the azetidine nitrogen of the radical anion leadsto spontaneous cleavage of the C5-N4' bond. In the cation radical pathway, cleavage of the C6-C4' bondfollowed by cleavage of the C5-O4' or the C5-N4' bond is more favorable kinetically than cleavage in thereverse order. We also found that the Dewar valence isomer can be reversed to the (6-4) product by bothradical anion and radical cation pathways, though the anionic pathway has a much lower barrier. Thesecalculations are in accord with the observation that the Dewar valence isomer is also reversed to the parentnucleotides by (6-4) photolyase, though much less efficiently than the (6-4) products.