Wójcik Anna, Radoń Mariusz, Borowski Tomasz
Department of Computational Biophysics and Bioinformatics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , ul. Gronostajowa 7, 30-387 Cracow, Poland.
Department of Chemistry, Jagiellonian University , ul. Ingardena 3, 30-060 Cracow, Poland.
J Phys Chem A. 2016 Mar 3;120(8):1261-74. doi: 10.1021/acs.jpca.5b12311. Epub 2016 Feb 23.
Four mechanisms previously proposed for dioxygen activation catalyzed by α-keto acid dependent oxygenases (α-KAO) were studied with dispersion-corrected DFT methods employing B3LYP and TPSSh functionals in combination with triple-ζ basis set (cc-pVTZ). The aim of this study was to revisit mechanisms suggested in the past decade and resolve remaining issues related to dioxygen activation. Mechanism A, which runs on the quintet potential energy surface (PES) and includes formation of an Fe(III)-superoxide radical anion complex, subsequent oxidative decarboxylation, and O-O bond cleavage, was found to be most likely. However, mechanism B taking place on the septet PES involves a rate limiting barrier comparable to the one found for mechanism A, and thus it cannot be excluded, though two other mechanisms (C and D) were ruled out. Mechanism C is a minor variation of mechanism A, whereas mechanism D proceeds through formation of a triplet Fe(IV)-alkyl peroxo bridged intermediate. The study covered also full optimization of relevant minimum energy crossing points (MECPs). The relative energy of critical intermediates was also studied with the CCSD(T) method in order to benchmark TPSSh and B3LYP functionals with respect to their credibility in predicting relative energies of septet and triplet spin states of the ternary enzyme-Fe-α-keto glutarate (α-KG)-O2 complex.
利用采用B3LYP和TPSSh泛函并结合三重ζ基组（cc-pVTZ）的色散校正密度泛函理论（DFT）方法，研究了先前提出的由α-酮酸依赖性加氧酶（α-KAO）催化双氧活化的四种机制。本研究的目的是重新审视过去十年中提出的机制，并解决与双氧活化相关的遗留问题。发现机制A在五重态势能面（PES）上运行，包括形成Fe(III)-超氧自由基阴离子络合物、随后的氧化脱羧和O-O键断裂，是最有可能的。然而，在七重态势能面上发生的机制B涉及一个与机制A相当的速率限制势垒，因此不能排除，尽管另外两种机制（C和D）被排除。机制C是机制A的一个微小变体，而机制D通过形成三重态Fe(IV)-烷基过氧桥连中间体进行。该研究还包括对相关最小能量交叉点（MECP）的完全优化。还使用CCSD(T)方法研究了关键中间体的相对能量，以便就TPSSh和B3LYP泛函在预测三元酶-Fe-α-酮戊二酸（α-KG）-O2络合物的七重态和三重态自旋态相对能量方面的可信度进行基准测试。
