Studies on the mechanism of aldehyde oxidase and xanthine oxidase.
Studies on the mechanism of aldehyde oxidase and xanthine oxidase.
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DOI：
10.1021/jo801053u
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发表时间：
2008-12-05
期刊：
影响因子：
--
通讯作者：
Jones JP
中科院分区：
文献类型：
--
作者：
Alfaro JF;Jones JP
DFT计算支持了6-取代4-喹唑啉酮sp2碳上黄嘌呤氧化酶和醛氧化酶氢化物置换的协调机制。过渡态结构的变化表明，C-O键在过渡态几乎完全形成，过渡态的变化是反哈蒙德的，反应速度越快，C-H和C-O键的长度越接近生成物。过渡态的C-O键长度形成在90%左右。然而，碳氢键只有80%的断裂。这导致了一个非常四面体的过渡态，O-C-N角为109度。因此，在机理一致的情况下，断裂的碳氢键反键轨道并没有受到亲核试剂的直接攻击，而是在几乎完全形成四面体过渡态后发生氢化物位移。为了支持这一点，C=N键在过渡态中被延长，表明对亲电碳的攻击是通过添加C=N键而发生的，氮上的负电荷增加。这些计算准确地再现了实验反应速率的差异，并倾向于支持这一机制。
DFT calculations support a concerted mechanism for xanthine oxidase and aldehyde oxidase hydride displacement from the sp2 carbon of 6-substituted 4-quinazolinones. The variations in transition state structure show that C-O bond formation is nearly complete in the transition state and the transition state changes are anti-Hammond with the C-H and C-O bond lengths being more product-like for the faster reactions. The C-O bond length in the transition state is around 90% formed. However, the C-H bond is only about 80% broken. This leads to a very tetrahedral transition state with an O-C-N angle of 109 degrees. Thus, while the mechanism is concerted, the anti-bonding orbital of the C-H bond that is broken is not directly attacked by the nucleophile and instead hydride displacement occurs after almost complete tetrahedral transition state formation. In support of this the C=N bond is lengthened in the transition state indicating that attack on the electrophilic carbon occurs by addition to the C=N bond with negative charge increasing on the nitrogen. Differences in experimental reaction rates are accurately reproduced by these calculations, and tend to support this mechanism.
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影响因子：
2.2
作者：
Arteca, Gustavo A.;Tapia, O.
通讯作者：
Tapia, O.
影响因子：
2.7
作者：
Jones, P;Atack, JR;MacLeod, AM
通讯作者：
MacLeod, AM
影响因子：
15
作者：
Amano, Tatsuo;Ochi, Noriaki;Sakaki, Shigeyoshi
通讯作者：
Sakaki, Shigeyoshi
影响因子：
15
作者：
Doonan, CJ;Stockert, A;George, GN
通讯作者：
George, GN
影响因子：
2.9
作者：
Obach, RS;Huynh, P;Beedham, C
通讯作者：
Beedham, C