methyl phenyl 4-nitrophenyl phosphate | 846-02-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: methyl phenyl 4-nitrophenyl phosphate
• 英文别名: Methyl-phenyl-<4-nitro-phenyl>-phosphat；Methyl phenyl p-nitrophenyl phosphate；methyl (4-nitrophenyl) phenyl phosphate
• CAS: 846-02-6
• 化学式: C₁₃H₁₂NO₆P
• 分子量: 309.215
• InChiKey: BUIUQBWAKOIBPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  90.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl phenyl 4-nitrophenyl phosphate 在 钴 CHES buffer 、 Pseudomonas diminuta phosphotriesterase G₆₀A mutant 作用下， 以 乙腈 为溶剂， 反应 0.75h， 以95%的产率得到(R)-Phosphoric acid methyl ester 4-nitro-phenyl ester phenyl ester
  参考文献：
  名称：

  合理设计的磷酸三酯酶突变体，用于手性有机磷酸酯的制备规模分离

  摘要：

  将催化有机磷酸三酯中酸性最强的酚取代基的水解。水解的总速率在很大程度上取决于离去基团苯酚的 pKa。4b 为了增强野生型酶表现出的底物立体选择性，我们设计并表征了 PTE 的几种定点突变体。已确定 PTE 活性位点内的三个区域（小基团、大基团和离去基团）与连接到典型底物磷中心的三个取代基相互作用。7 在结合底物类似物存在的情况下，使用 PTE 的 X 射线晶体结构对这些子位点进行图形定位。这些结合子位点的相对大小似乎在建立野生型 PTE 的立体选择性特性中起主导作用。8 因此，当通过将 Gly60 突变为丙氨酸残基来减小小亚位点的大小时，观察到的突变酶对 SP 异构体水解的立体选择性显着增强。对于底物 I、II 和 III 的外消旋对，SP 异构体的 kcat/Km 值比相应的 RP 异构体高 10 到 400 倍，而 RP 异构体的 kcat/Km 值高 10 000 到 15 000 倍。

  DOI：

  10.1021/ja002546r

文献信息

• Interrogation of the Substrate Profile and Catalytic Properties of the Phosphotriesterase from <i>Sphingobium</i> sp. Strain TCM1: An Enzyme Capable of Hydrolyzing Organophosphate Flame Retardants and Plasticizers
  作者：Dao Feng Xiang、Andrew N. Bigley、Zhongjie Ren、Haoran Xue、Kenneth G. Hull、Daniel Romo、Frank M. Raushel

  DOI：10.1021/acs.biochem.5b01144

  日期：2015.12.29

  The most familiar organophosphorus compounds are the neurotoxic insecticides and nerve agents. A related group of organophosphorus compounds, the phosphotriester plasticizers and flame retardants, has recently become widely used. Unlike the neurotoxic phosphotriesters, the plasticizers and flame retardants lack an easily hydrolyzable bond. While the hydrolysis of the neurotoxic organophosphates by phosphotriesterase enzymes is well-known, the lack of a labile bond in the flame retardants and plasticizers renders them inert to typical phosphotriesterases. A phosphotriesterase from Sphingobium sp. strain TCM1 (Sb-PTE) has recently been reported to catalyze the hydrolysis of organophosphorus flame retardants. This enzyme has now been expressed in Escherichia coli, and the activity with a wide variety of organophosphorus substrates has been characterized and compared to the activity of the well-known phosphotriesterase from Pseudomonas diminuta (Pd-PTE). Structure prediction suggests that Sb-PTE has a β-propeller fold, and homology modeling has identified a potential mononuclear manganese binding site. Sb-PTE exhibits catalytic activity against typical phosphotriesterase substrates such as paraoxon, but unlike Pd-PTE, Sb-PTE is also able to effectively hydrolyze flame retardants, plasticizers, and industrial solvents. Sb-PTE can hydrolyze both phosphorus–oxygen bonds and phosphorus–sulfur bonds, but not phosphorus–nitrogen bonds. The best substrate for Sb-PTE is the flame retardant triphenyl phosphate with a kcat/Km of 1.7 × 106 M–1 s–1. Quite remarkably, Sb-PTE is also able to hydrolyze phosphotriesters with simple alcohol leaving groups such as tributyl phosphate (kcat/Km = 40 M–1 s–1), suggesting that this enzyme could be useful for the bioremediation of a wide variety of organophosphorus compounds.

  最常见的有机磷化合物是神经毒性杀虫剂和神经毒剂。与其相关的一组有机磷化合物，即磷酰三酯增塑剂和阻燃剂，近来已被广泛使用。与神经毒性磷酰三酯不同，增塑剂和阻燃剂缺乏易于水解的键。尽管磷酰三酯酶对神经毒性有机磷酸盐的水解已为人所熟知，但阻燃剂和增塑剂中缺乏活性键使得它们对典型的磷酰三酯酶不起反应。近期有报道称，来自淡紫拟青霉菌株TCM1（Sb-PTE）的一种磷酰三酯酶能够催化有机磷阻燃剂的水解。这种酶现已在大肠杆菌中表达，其对多种有机磷底物的活性已被鉴定并与其从矮小假单胞菌（Pd-PTE）中提取的活性进行了比较。结构预测表明，Sb-PTE具有β-螺旋桨折叠结构，同源建模揭示了一个潜在的单核锰结合位点。Sb-PTE表现出对如对氧磷等典型磷酰三酯酶底物的催化活性，但与Pd-PTE不同，Sb-PTE还能有效水解阻燃剂、增塑剂和工业溶剂。Sb-PTE能够水解磷氧键和磷硫键，但不是磷氮键。Sb-PTE的最佳底物是阻燃剂三苯基磷酸酯，其kcat/Km值为1.7 × 106 M–1 s–1。非常值得注意的是，Sb-PTE还能够水解具有简单醇离去基团的磷酰三酯，如三丁基磷酸酯（kcat/Km = 40 M–1 s–1），这表明该酶在广泛的有机磷化合物生物修复方面可能非常有用。
• Substrate and stereochemical specificity of the organophosphorus acid anhydrolase from Alteromonas sp. JD6.5 toward p -nitrophenyl phosphotriesters
  作者：Craig M. Hill、Feiyue Wu、Tu-Chen Cheng、Joseph J. DeFrank、Frank M. Raushel

  DOI：10.1016/s0960-894x(00)00213-4

  日期：2000.6

  The enzyme OPAA hydrolyzes p-nitrophenyl phosphotriesters bearing substituents at the phosphorus center ranging in size from methyl to phenyl. The enzyme exhibits stereoselectivity toward the hydrolysis of chiral substrates with a preference for the Sp enantiomer. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Rationally Engineered Mutants of Phosphotriesterase for Preparative Scale Isolation of Chiral Organophosphates
  作者：Feiyue Wu、Wen-Shan Li、Misty Chen-Goodspeed、Miguel A. Sogorb、Frank M. Raushel

  DOI：10.1021/ja002546r

  日期：2000.10.1

  catalyze the hydrolysis of the most acidic phenolic substituent from an organophosphate triester. The overall rate of hydrolysis is very much dependent on the pKa of the leaving group phenol. 4b To enhance the substrate stereoselectivity exhibited by the wildtype enzyme, we designed and characterized several site-directed mutants of PTE. Three regions within the active site of PTE (small, large, and

  将催化有机磷酸三酯中酸性最强的酚取代基的水解。水解的总速率在很大程度上取决于离去基团苯酚的 pKa。4b 为了增强野生型酶表现出的底物立体选择性，我们设计并表征了 PTE 的几种定点突变体。已确定 PTE 活性位点内的三个区域（小基团、大基团和离去基团）与连接到典型底物磷中心的三个取代基相互作用。7 在结合底物类似物存在的情况下，使用 PTE 的 X 射线晶体结构对这些子位点进行图形定位。这些结合子位点的相对大小似乎在建立野生型 PTE 的立体选择性特性中起主导作用。8 因此，当通过将 Gly60 突变为丙氨酸残基来减小小亚位点的大小时，观察到的突变酶对 SP 异构体水解的立体选择性显着增强。对于底物 I、II 和 III 的外消旋对，SP 异构体的 kcat/Km 值比相应的 RP 异构体高 10 到 400 倍，而 RP 异构体的 kcat/Km 值高 10 000 到 15 000 倍。