Bassan Arianna, Blomberg Margareta R A, Siegbahn Per E M
Department of Physics, Stockholm Center for Physics, Astronomy and Biotechnology, Stockholm University, 106 91 Stockholm, Sweden.
J Biol Inorg Chem. 2004 Jun;9(4):439-52. doi: 10.1007/s00775-004-0537-0. Epub 2004 Mar 24.
The catalytic mechanism of naphthalene 1,2-dioxygenase has been investigated by means of hybrid density functional theory. This Rieske-type enzyme, which contains an active site hosting a mononuclear non-heme iron(II) complex, uses dioxygen and two electrons provided by NADH to carry out the cis-dihydroxylation of naphthalene. Since a (hydro)peroxo-iron(III) moiety has been proposed to be involved in the catalytic cycle, it was probed whether and how this species is capable of cis-dihydroxylation of the aromatic substrate. Different oxidation and protonation states of the Fe-O2 complex were studied on the basis of the crystal structure of the enzyme with oxygen bound side-on to iron. It was found that feasible reaction pathways require a protonated peroxo ligand, FeIII-OOH; the deprotonated species, the peroxo-iron(III) complex, was found to be inert toward naphthalene. Among the different chemical patterns which have been explored, the most accessible one involves an epoxide intermediate, which may subsequently evolve toward an arene cation, and finally to the cis-diol. The possibility that an iron(V)-oxo species is formed prior to substrate hydroxylation was also examined, but found to implicate a rather high energy barrier. In contrast, a reasonably low barrier might lead to a high-valent iron-oxo species [i.e. iron(IV)-oxo] if a second external electron is supplied to the mononuclear iron center before dioxygenation.
利用杂化密度泛函理论研究了萘1,2 -双加氧酶的催化机制。这种里氏型酶含有一个活性位点，其中有一个单核非血红素铁（II）配合物，它利用二氧和由NADH提供的两个电子对萘进行顺式二羟基化反应。由于有人提出催化循环中涉及一个（氢）过氧 - 铁（III）部分，因此研究了该物种是否以及如何能够对芳香族底物进行顺式二羟基化反应。基于氧气以侧基方式与铁结合的酶的晶体结构，研究了Fe - O₂配合物的不同氧化态和质子化态。结果发现，可行的反应途径需要一个质子化的过氧配体，即FeIII - OOH；而去质子化的物种，即过氧 - 铁（III）配合物，被发现对萘是惰性的。在探索的不同化学模式中，最容易实现的一种涉及一个环氧化物中间体，它随后可能演变成一个芳烃阳离子，最终生成顺式二醇。还研究了在底物羟基化之前形成铁（V） - 氧物种的可能性，但发现这涉及一个相当高的能垒。相比之下，如果在双加氧反应之前向单核铁中心提供第二个外部电子，则可能会有一个合理的低能垒导致形成高价铁 - 氧物种[即铁（IV） - 氧]。
