Functional Models for Vanadium Haloperoxidase: Reactivity and Mechanism of Halide Oxidation

A series of oxoperoxovanadium(V) complexes (ligands: H3nta = nitrilotriacetic acid, H3heida = N-(2-hydroxyethyl)iminodiacetic acid, H2ada = N-(2-amidomethyl)iminodiacetic acid, Hbpg = N,N-bis(2-pyridylmethyl)glycine, and tpa = N,N,N-tris(2-pyridylmethyl)amine) were characterized as functional models for the vanadium haloperoxidase enzymes. The crystal structures of K[VO(O2)Hheida], K[VO(O2)ada], [VO(O2)bpg], and H[VO(O2)bpg]2(ClO4) were obtained. These complexes all possess a distorted pentagonal bipyramidal coordination sphere containing a side-on bound peroxide. In the presence of sufficient acid equivalents these complexes catalyze the two-electron oxidation of bromide or iodide by peroxide. Halogenation of an organic substrate was demonstrated by following the visible conversion of Phenol Red to Bromophenol Blue. In the absence of substrate, dioxygen can be generated by the halide-assisted disproportionation of hydrogen peroxide. In addition, some of these complexes can efficiently catalyze the peroxidative halogenation reaction, performing multiple turnovers in minutes. The kinetic analysis of the halide oxidation reaction indicates a mechanism which is first order in protonated peroxovanadium complex and halide. The bimolecular rate constants for both bromide and iodide oxidation were determined, with the iodide rates being approximately 5−6 times faster than the bromide rates. The rate constants obtained for bromide oxidation range from a maximum of 280 M-1 s-1 for the Hheida complex to a minimum of 21 M-1 s-1 for the Hbpg complex. The pKa of activation for each complex in acetonitrile was determined to range from 5.4 to 6.0. On the basis of the chemistry observed for these model compounds, a mechanism of halide oxidation and a detailed catalytic cycle are proposed for the vanadium haloperoxidase enzyme.本研究合成并表征了一系列氧过氧钒(V)配合物，其配体包括：次氮基三乙酸（nitrilotriacetic acid, H3nta）、N-(2-羟乙基)亚氨基二乙酸（N-(2-hydroxyethyl)iminodiacetic acid, H3heida）、N-(2-氨甲基)亚氨基二乙酸（N-(2-amidomethyl)iminodiacetic acid, H2ada）、N,N-双(2-吡啶甲基)甘氨酸（N,N-bis(2-pyridylmethyl)glycine, Hbpg）以及N,N,N-三(2-吡啶甲基)胺（N,N,N-tris(2-pyridylmethyl)amine, tpa），该系列配合物被用作钒卤代过氧化物酶的功能模拟体系。解析得到了K[VO(O2)Hheida]、K[VO(O2)ada]、[VO(O2)bpg]及H[VO(O2)bpg]2(ClO4)的晶体结构。该类配合物均具有包含侧基配位过氧根的畸变五角双锥配位环境。在足量质子供体（酸当量）存在时，该系列配合物可催化过氧化物将溴离子或碘离子发生两电子氧化反应。通过观测酚红（Phenol Red）可视转化为溴酚蓝（Bromophenol Blue），证实了该体系可实现有机底物的卤化修饰。当无反应底物时，可通过卤离子辅助的过氧化氢歧化反应生成氧气。此外，部分该系列配合物可高效催化过氧化物介导的卤化反应，可在数分钟内完成多次催化循环。对卤离子氧化反应的动力学分析表明，其反应速率对质子化过氧钒配合物及卤离子均呈现一级动力学特征。测定了溴离子与碘离子氧化过程的双分子速率常数，其中碘离子的氧化速率约为溴离子的5~6倍。溴离子氧化的速率常数范围为：Hheida配合物的最大值280 M⁻¹·s⁻¹，至Hbpg配合物的最小值21 M⁻¹·s⁻¹。在乙腈溶剂中测定的各配合物的活化pKa值介于5.4~6.0之间。基于上述模拟化合物的反应特性，本研究提出了卤离子氧化的反应机制，以及钒卤代过氧化物酶的详细催化循环路径。