p-Nitrophenyl-methylphosphonat | 1832-64-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: p-Nitrophenyl-methylphosphonat
• 英文别名: p-Nitrophenyl-methylphosphonsaeure；Methyl-phosphonic acid mono-(4-nitro-phenyl) ester；methyl-(4-nitrophenoxy)phosphinic acid
• CAS: 1832-64-0
• 化学式: C₇H₈NO₅P
• 分子量: 217.118
• InChiKey: VJPXTXIEAOSJBR-UHFFFAOYSA-N

物化性质

• 熔点：
  90-90.5 °C
• 沸点：
  382.6±44.0 °C(Predicted)
• 密度：
  1.477±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  p-Nitrophenyl-methylphosphonat 在 四丁基氟化铵 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 24.17h， 生成 2-fluoroethyl 4-nitrophenyl methylphosphonate
  参考文献：
  名称：

  Synthesis and anti-acetylcholinesterase properties of novel β- and γ-substituted alkoxy organophosphonates

  摘要：

  Activated organophosphate (OP) insecticides and chemical agents inhibit acetylcholinesterase (AChE) to form OP-AChE adducts. Whereas the structure of the OP correlates with the rate of inhibition, the structure of the OP-AChE adduct influences the rate at which post-inhibitory reactivation or aging phenomena occurs. In this report, we prepared a panel of beta-substituted ethoxy and gamma-substituted propoxy phosphonoesters of the type p-NO2PhO-P(X)(R)[(O(CH2)(n)Z] (R = Me, Et; X = O, S; n = 2, 3; Z = halogen, OTs) and examined the inhibition of three AChEs by select structures in the panel. The beta-fluoroethoxy methylphosphonate analog (R = Me, Z = F, n = 2) was the most potent anti-AChE compound comparable (k(i); similar to 6 x 10(6) M-1 min(-1)) to paraoxon against EEAChE. Analogs with Z = Br, I, or OTs were weak inhibitors of the AChEs, and methyl phosphonates (R = Me) were more potent than the corresponding ethyl phosphonates (R = Et). As expected, analogs with a thionate linkage (P=S) were poor inhibitors of the AChEs. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.010
• 作为产物：
  描述：

  二(4-硝基苯基)甲基膦酸酯 在 1-氨基癸烷 、 水 、 溴代十六烷基吡啶 作用下， 生成 p-Nitrophenyl-methylphosphonat
  参考文献：
  名称：

  疏水胺对溴化十六烷基吡啶胶束溶液中双(对硝基苯基)甲基膦酸酯水解的影响

  摘要：

  研究了双（对硝基苯基）甲基膦酸酯在脂肪族伯胺存在下在十六烷基溴化吡啶鎓的胶束水溶液中的水解动力学。根据一般碱性催化机理，该反应通过碱性水解和胺催化水解两种途径进行。这些路线的贡献和胶束的催化作用取决于胺的疏水性。发现了不同类型胶束的形成，并通过张力测定法和具有磁场脉冲梯度的高分辨率 1 H NMR 光谱确定了它们的特征参数。

  DOI：

  10.1007/bf02494670

文献信息

• Catalysis of the hydrolysis of esters of phosphorus acids byn-decylammonium chloride /n-decylamine mixed micelles
  作者：R. F. Bakeeva、L. A. Kudryameva、V. E. Bel'skii、S. B. Fedorov、B. E. Ivanov

  DOI：10.1007/bf01457772

  日期：1996.8

  The effect ofn-decylammonium chloride/n-decylamine mixed micelles on the rate of hydrolysis of aryl esters of acids of four-coordinate phosphorus was studied spectrophotometrically. The shape of the concentration curves is characteristic of the micellar catalysis reactions. The binding constants of the substrate, critical micelle concentrations, and the rate constants in the micellar phase were determined

  采用分光光度法研究了正癸基氯化铵/正癸胺混合胶束对四配位磷酸芳基酯水解速率的影响。浓度曲线的形状是胶束催化反应的特征。确定了底物的结合常数、临界胶束浓度和胶束相中的速率常数。显示了基板结构对这些参数的特定影响。
• Balancing Specificity and Promiscuity in Enzyme Evolution: Multidimensional Activity Transitions in the Alkaline Phosphatase Superfamily
  作者：Bert van Loo、Christopher D. Bayer、Gerhard Fischer、Stefanie Jonas、Eugene Valkov、Mark F. Mohamed、Anastassia Vorobieva、Celine Dutruel、Marko Hyvönen、Florian Hollfelder

  DOI：10.1021/jacs.8b10290

  日期：2019.1.9

  adaptation by their capacity to promote multiple reactions. We employ a systematic comparative study of structure, sequence, and substrate specificity to track the evolution of specificity and reactivity between promiscuous members of clades of the alkaline phosphatase (AP) superfamily. Construction of a phylogenetic tree of protein sequences maps out the likely transition zone between arylsulfatases (ASs)

  高度熟练、混杂的酶可以成为功能进化的跳板，能够通过促进多重反应的能力避免在适应过程中丧失功能。我们采用结构、序列和底物特异性的系统比较研究来跟踪碱性磷酸酶 (AP) 超家族分支的混杂成员之间的特异性和反应性的演变。构建蛋白质序列的系统发育树，绘制出芳基硫酸酯酶 (AS) 和膦酸单酯水解酶 (PMH) 之间可能的过渡区。动力学分析表明，所有被表征的酶都具有四种不同的化学磷酸酯酶和磺酯酶活性，其初级反应的速率加速范围为 1011 至 1017 倍，混杂反应的速率加速范围为 109 至 1012 倍，表明催化性滥交在 AP 超家族中普遍存在。这种功能表征和晶体学揭示了一类新的 AS，它在序列上与已知的 PMH 非常相似，以至于没有被认为在功能上存在差异。基于对“过渡中”催化滥交快照的分析，我们开发了可能的模型，允许功能进化并确定多种活动之间的权衡方案。对于新的 AS，我们观察到很大程度上不变的底
• Cholinesterase Inhibitors
  申请人：Thompson Charles M.

  公开号：US20130343994A1

  公开（公告）日：2013-12-26

  The invention provides compounds that inhibit cholinesterases, such as acetylcholinesterase and butyrylcholinesterase. Such compounds are useful to prevent or treat exposure of a patient (e.g., a human) to an organophosphoric nerve agent (e.g., sarin and VX) or to treat a patient suffering from a neurodegenerative disorder such as Alzheimer's Disease or Lewy Body Dementia. The compounds are further useful as diagnostic tools for use in medical or research radiography (e.g., positron emission tomography) when synthesized with a radionuclide (e.g., [18F]. Synthetic schemes to produce such compounds are also provided.

  该发明提供了抑制胆碱酯酶的化合物，例如乙酰胆碱酯酶和丁酰胆碱酯酶。这些化合物可用于预防或治疗患者（例如人类）暴露于有机磷神经毒剂（例如沙林和VX）或治疗患有神经退行性疾病（如阿尔茨海默病或路易体痴呆症）的患者。这些化合物还可作为诊断工具用于医学或研究放射学（例如正电子发射断层扫描）时，当与放射性核素（例如[18F]）合成时。还提供了用于合成这些化合物的合成方案。
• Study of <i>para</i>-Quinone Methide Precursors toward the Realkylation of Aged Acetylcholinesterase
  作者：Ryan J. Yoder、Qinggeng Zhuang、Jeremy M. Beck、Andrew Franjesevic、Travis G. Blanton、Sydney Sillart、Tyler Secor、Leah Guerra、Jason D. Brown、Carolyn Reid、Craig A. McElroy、Özlem Doğan Ekici、Christopher S. Callam、Christopher M. Hadad

  DOI：10.1021/acsmedchemlett.7b00037

  日期：2017.6.8

  capable of reactivating inhibited AChE. There are no known therapeutic agents to reverse the aging process or treat aged AChE. Quinone methides (QMs) have been shown to alkylate phosphates under physiological conditions. In this study, a small library of novel quinone methide precursors (QMPs) has been synthesized and examined as potential alkylating agents against model nucleophiles, including a model phosphonate

  乙酰胆碱酯酶（AChE）是一种必需的酶，可以被有机磷（OP）化合物（包括神经毒剂）靶向。暴露于OPs后，AChE磷酸化（被抑制）并经历后续的老化过程，其中OP-AChE加合物被脱烷基。老化的AChE无法水解乙酰胆碱，导致神经递质在中枢神经系统（CNS）和其他部位的积累。当前的治疗剂仅能够重新激活抑制的AChE。没有已知的治疗剂可以逆转衰老过程或治疗衰老的AChE。醌甲基化物（QMs）已显示在生理条件下可使磷酸烷基化。在这项研究中，我们合成了一个小型的新型醌甲基前体（QMP）库，并将其作为针对模型亲核试剂的潜在烷基化剂进行了研究，包括模型膦酸酯。已经进行了计算研究，以评估QMP对衰老的AChE活性位点的亲和力，并且已经进行了电鳗AChE的初步测试。
• Mechanism and Transition State Structure of Aryl Methylphosphonate Esters Doubly Coordinated to a Dinuclear Cobalt(III) Center
  作者：Guoqiang Feng、Eric A. Tanifum、Harry Adams、Alvan C. Hengge、Nicholas H. Williams

  DOI：10.1021/ja904134n

  日期：2009.9.9

  to that of a phosphate monoester complex with the same leaving group, rather than the isoelectronic diester complex. The data from these model systems parallel the observation that in protein phosphatase-1, which has an active site that resembles the structures of these complexes, the catalyzed hydrolysis of aryl methylphosphonates and aryl phosphates are much more similar to one another than the uncomplexed

  研究了每种与双核 Co(III) 配合物配位的五种膦酸酯的反应性 ([Co(2)(tacn)(2)(OH)(2)O(2)P(Me)OAr}](3+ ); tacn = 1,4,7-三氮杂环壬烷; 取代基 = mF, p-NO(2) (1a); p-NO(2) (1b); m-NO(2) (1c); p-Cl ( 1d)；未取代的(1e))。1a 到 1e 中膦酸酯的水解是特定碱催化的，并通过分子内氧化物攻击桥接膦酸酯而发生。这些数据定义了 -1.12 的 Brønsted beta(lg)，比未复合的膦酸酯的水解 (-0.69) 更负面。对于 1b，离去基团中的动力学同位素效应为 (18)k(lg) = 1.0228 和 (15)k = 1.0014，在非桥连磷酰氧 (18)k(nonbridge) = 0.9954 和亲核氧（ 18)k(nuc) = 1.0105。KIE 和 beta(lg)