Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA.
J Org Chem. 2013 Sep 6;78(17):8585-93. doi: 10.1021/jo401274u. Epub 2013 Aug 12.
DFT calculations presented for C(4a)-hydroperoxyflavin (C(4a)-FLHOOH) at the B3LYP/6-311+G(d,p) level suggest a new mechanism for the elimination of H2O2. The calculated activation barrier for a concerted four-centered elimination (ΔE(‡) = 32.86 kcal/mol) strongly suggests that in the absence of interactions with the local environment a spontaneous elimination is not feasible. A proton shuttle from the N5 hydrogen to the proximal oxygen of the OOH moiety involving three water molecules has an activation barrier that is reduced to 17.11 kcal/mol. Calculations that utilize CH3OH to model the role of a local Thr or Ser residue shows that an alcohol functionality hydrogen bonded to the N5 H-atom can catalyze the elimination of H2O2 with a free energy of activation of 21.5 kcal/mol. Interaction of amines and amide residues (CH3NH2 and CH3(C═O)NH2) with the N5 locus of C(4a)-hydroperoxyflavin markedly reduce the activation barrier for H2O2 elimination relative to the concerted pathway. Proton transfer from a COOH group (ΔG(‡) = 8.36 kcal/mol) or the NH2 group of a positively charged Arg model (ΔG(‡) = 9.99 kcal/mol) to the proximal oxygen of the OOH moiety of C(4a)-FLHOOH in the TS for H2O2 elimination strongly enhances elimination of H2O2.
在 B3LYP/6-311+G(d,p) 水平下对 C(4a)-过氧黄素（C(4a)-FLHOOH）进行的 DFT 计算表明，对于 H2O2 的消除存在一种新的机制。协同的四中心消除的计算活化势垒（ΔE(‡) = 32.86 kcal/mol）强烈表明，在没有与局部环境相互作用的情况下，自发消除是不可行的。质子从 N5 氢到 OOH 部分的近端氧的转移，涉及三个水分子，其活化势垒降低到 17.11 kcal/mol。利用 CH3OH 模拟局部 Thr 或 Ser 残基的作用的计算表明，与 N5 H-原子氢键结合的醇官能团可以催化 H2O2 的消除，其活化自由能为 21.5 kcal/mol。胺和酰胺残基（CH3NH2 和 CH3(C═O)NH2）与 C(4a)-过氧黄素的 N5 位置的相互作用显著降低了相对于协同途径的 H2O2 消除的活化势垒。从 COOH 基团（ΔG(‡) = 8.36 kcal/mol）或带正电荷 Arg 模型的 NH2 基团（ΔG(‡) = 9.99 kcal/mol）向 C(4a)-FLHOOH 的 OOH 部分的近端氧的质子转移在 H2O2 消除的 TS 中强烈促进 H2O2 的消除。
