8-(2-甲基苯氧基)-7,9-二氧杂-8lambda5-磷杂双环[4.4.0]癸-1,3,5-三烯 8-氧化物 | 1222-87-3

• 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
• 中文名称: 8-(2-甲基苯氧基)-7,9-二氧杂-8lambda5-磷杂双环[4.4.0]癸-1,3,5-三烯 8-氧化物
• 中文别名: 8-(2-甲基苯氧基)-7,9-二氧杂-8lambda5-磷杂双环[4.4.0]癸-1,3,5-三烯8-氧化物
• 英文名称: 4H-1,3,2-Benzodioxaphosphorin, 2-(2-methylphenoxy)-, 2-oxide
• 英文别名: 2-(O-o-cresyl)-4H-1,3,2-benzodioxaphosphorin-2-oxide；2-(ortho-cresyl)-4H-1,2,3-benzodioxaphosphoran-2-one；2-(ortho-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one；2-(o-cresyl)-4H-1,3,2-benzodioxaphosphorin-2-oxide；cyclic tolyl saligenin phosphate；o-cresyl saligenin phosphate；2-(2-methylphenoxy)-4H-1,3,2λ5-benzodioxaphosphinine 2-oxide
• CAS: 1222-87-3
• 化学式: C₁₄H₁₃O₄P
• 分子量: 276.229
• InChiKey: LKQSEFCGKYFESN-UHFFFAOYSA-N

物化性质

• 沸点：
  362.4±42.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-(2-甲基苯氧基)-7,9-二氧杂-8lambda5-磷杂双环[4.4.0]癸-1,3,5-三烯 8-氧化物 在 human acetylcholinesterase 作用下， 以 甲醇 、 乙腈 为溶剂， 生成 水杨醇
  参考文献：
  名称：

  Reaction of Cresyl Saligenin Phosphate, the Organophosphorus Agent Implicated in Aerotoxic Syndrome, with Human Cholinesterases: Mechanistic Studies Employing Kinetics, Mass Spectrometry, and X-ray Structure Analysis

  摘要：

  Aerotoxic syndrome is assumed to be caused by exposure to tricresyl phosphate (TCP), an antiwear additive in jet engine lubricants and hydraulic fluid. CBDP (2-(ortho-cresyl)4H-1,2,3-benzodioxaphosphoran-2-one) is the toxic metabolite of triortho-cresylphosphate, a component of TCP. Human butyrylcholinesterase (BChE; EC 3.1.1.8) and human acetylcholinesterase (AChE; EC 3.1.1.7) are irreversibly inhibited by CBDP. The bimolecular rate constants of inhibition (k(i)), determined under pseudo-first-order conditions, displayed a biphasic time course of inhibition with k(i) of 1.6 x 10(8) M-1 min(-1) and 2.7 x 10(7) M-1 min(-1) for E and E' forms of BChE. The inhibition constants for AChE were 1 to 2 orders of magnitude slower than those for BChE. CBDP-phosphorylated cholinesterases are nonreactivatable due to ultra fast aging. Mass spectrometry analysis showed an initial BChE adduct with an added mass of 170 Da from cresylphosphate, followed by dealkylation to a structure with an added mass of 80 Da. Mass spectrometry in O-18-water showed that O-18 was incorporated only during the final aging step to form phospho-serine as the final aged BChE adduct. The crystal structure of CBDP-inhibited BChE confirmed that the phosphate adduct is the ultimate aging product. CBDP is the first organophosphorus agent that leads to a fully dealkylated phospho-serine BChE adduct.

  DOI：

  10.1021/tx100447k

文献信息

• Development of diagnostics in the search for an explanation of aerotoxic syndrome
  作者：Lawrence M. Schopfer、Clement E. Furlong、Oksana Lockridge

  DOI：10.1016/j.ab.2010.04.032

  日期：2010.9

  Aerotoxic syndrome is assumed to be caused by exposure to tricresyl phosphate, an additive in engine lubricants and hydraulic fluids that is activated to the toxic 2-(ortho-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (CBDP). Currently, there is no laboratory evidence to support intoxication of airline crew members by CBDP. Our goal was to develop methods for testing in vivo exposure by identifying and characterizing biomarkers. Mass spectrometry was used to study the reaction of CBDP with human albumin, free tyrosine, and human butyrylcholinesterase. Human albumin made a covalent bond with CBDP, adding a mass of 170 amu to Tyr411 to yield the o-cresyl phosphotyrosine derivative. Human butyrylcholinesterase made a covalent bond with CBDP on Ser198 to yield five adducts with added masses of 80, 108, 156, 170, and 186 amu. The most abundant adduct had an added mass of 80 amu from phosphate (HPO(3)), a surprising result given that no pesticide or nerve agent is known to yield phosphorylated serine with an added mass of 80 amu. The next most abundant adduct had an added mass of 170 amu to form o-cresyl phosphoserine. It is concluded that toxic gases or oil mists in cabin air may form adducts on plasma butyrylcholinesterase and albumin, detectable by mass spectrometry. (C) 2010 Elsevier Inc. All rights reserved.