2-{[bis(pyridin-2-ylmethyl)amino]methyl}-6-{[bis(6-pivaloylamidopyridin-2-ylmethyl)amino]methyl}-4-methylphenol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-{[bis(pyridin-2-ylmethyl)amino]methyl}-6-{[bis(6-pivaloylamidopyridin-2-ylmethyl)amino]methyl}-4-methylphenol
• 英文别名: N-[6-[[[3-[[bis(pyridin-2-ylmethyl)amino]methyl]-2-hydroxy-5-methylphenyl]methyl-[[6-(2,2-dimethylpropanoylamino)pyridin-2-yl]methyl]amino]methyl]pyridin-2-yl]-2,2-dimethylpropanamide
• 化学式: C₄₃H₅₂N₈O₃
• 分子量: 728.938
• InChiKey: HLWIHCQRENVFCU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  54
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-{[bis(pyridin-2-ylmethyl)amino]methyl}-6-{[bis(6-pivaloylamidopyridin-2-ylmethyl)amino]methyl}-4-methylphenol 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 72.0h， 以47%的产率得到2-[[Bis[(6-aminopyridin-2-yl)methyl]amino]methyl]-6-[[bis(pyridin-2-ylmethyl)amino]methyl]-4-methylphenol
  参考文献：
  名称：

  Dinuclear Zinc(II) Complexes with Hydrogen Bond Donors as Structural and Functional Phosphatase Models

  摘要：

  It is becoming increasingly apparent that the secondary coordination sphere can have a crucial role in determining the functional properties of biomimetic metal complexes. We have therefore designed and prepared a variety of ligands as metallo-hydrolase mimics, where hydrogen bonding in the second coordination sphere is able to influence the structure of the primary coordination sphere and the substrate binding. The assessment of a structure-function relationship is based on derivates of 2,6-bis{[bis(pyridin-2-ylmethyl)amino]methyl}-4-methylphenol (HBPMP = HL1) and 2-{[bis(pyridin-2-ylmethyl)amino]methy1}-64[(2-hydroxybenzyl)(pyridin-2-ylmethy)amino]methyl}-4-methylphenol (H2BPBPMP = H2L5), well-known phenolate-based ligands for metallo-hydrolase mimics. The model systems provide similar primary coordination spheres but site-specific modifications in the secondary coordination sphere. Pivaloylamide and amine moieties were chosen to mimic the secondary coordination sphere of the phosphatase models, and the four new ligands H3L2, H3L3, HL4, and H4L6 vary in the type and geometric position of the H-bond donors and acceptors, responsible for the positioning of the substrate and release of the product molecules. Five dinuclear Zn-II complexes were prepared and structurally characterized in the solid, and four also in solution. The investigation phosphatase activity of four model complexes illustrates the impact of the H-bonding network: the Michaelis-Menten constants (catalyst-substrate binding) for all complexes that support hydrogen bonding are smaller than for the reference complex, and this generally leads to higher catalytic efficiency and higher turnover numbers.

  DOI：

  10.1021/ic5009945
• 作为产物：
  描述：

  3-(氯甲基)-2-羟基-5-甲基苯甲醛 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 2-{[bis(pyridin-2-ylmethyl)amino]methyl}-6-{[bis(6-pivaloylamidopyridin-2-ylmethyl)amino]methyl}-4-methylphenol
  参考文献：
  名称：

  Dinuclear Zinc(II) Complexes with Hydrogen Bond Donors as Structural and Functional Phosphatase Models

  摘要：

  It is becoming increasingly apparent that the secondary coordination sphere can have a crucial role in determining the functional properties of biomimetic metal complexes. We have therefore designed and prepared a variety of ligands as metallo-hydrolase mimics, where hydrogen bonding in the second coordination sphere is able to influence the structure of the primary coordination sphere and the substrate binding. The assessment of a structure-function relationship is based on derivates of 2,6-bis{[bis(pyridin-2-ylmethyl)amino]methyl}-4-methylphenol (HBPMP = HL1) and 2-{[bis(pyridin-2-ylmethyl)amino]methy1}-64[(2-hydroxybenzyl)(pyridin-2-ylmethy)amino]methyl}-4-methylphenol (H2BPBPMP = H2L5), well-known phenolate-based ligands for metallo-hydrolase mimics. The model systems provide similar primary coordination spheres but site-specific modifications in the secondary coordination sphere. Pivaloylamide and amine moieties were chosen to mimic the secondary coordination sphere of the phosphatase models, and the four new ligands H3L2, H3L3, HL4, and H4L6 vary in the type and geometric position of the H-bond donors and acceptors, responsible for the positioning of the substrate and release of the product molecules. Five dinuclear Zn-II complexes were prepared and structurally characterized in the solid, and four also in solution. The investigation phosphatase activity of four model complexes illustrates the impact of the H-bonding network: the Michaelis-Menten constants (catalyst-substrate binding) for all complexes that support hydrogen bonding are smaller than for the reference complex, and this generally leads to higher catalytic efficiency and higher turnover numbers.

  DOI：

  10.1021/ic5009945

文献信息

• An Approach to More Accurate Model Systems for Purple Acid Phosphatases (PAPs)
  作者：Paul V. Bernhardt、Simone Bosch、Peter Comba、Lawrence R. Gahan、Graeme R. Hanson、Valeriu Mereacre、Christopher J. Noble、Annie K. Powell、Gerhard Schenk、Hubert Wadepohl

  DOI：10.1021/acs.inorgchem.5b00628

  日期：2015.8.3

  The active site of mammalian purple acid phosphatases (PAPs) have a dinuclear iron site in two accessible oxidation states (FeIII2 and FeIIIFeII), and the heterovalent is the active form, involved in the regulation of phosphate and phosphorylated metabolite levels in a wide range of organisms. Therefore, two sites with different coordination geometries to stabilize the heterovalent active form and

  哺乳动物紫色酸性磷酸酶（PAP）的活性位点具有双核铁位点，处于两个可访问的氧化态（Fe III 2和Fe III Fe II），杂价是活性形式，参与多种生物体中磷酸盐和磷酸化代谢物水平的调节。因此，据认为催化活性模型系统需要两个具有不同配位几何形状的位点以稳定异价活性形式，另外还具有氢键供体以使得能够固定底物并释放产物。已经详细研究了两个配体及其双核铁配合物。通过X射线晶体学，磁性和Mössbauer光谱学研究的固态结构和性质，以及通过质谱，电子，核磁共振（NMR），电子顺磁共振（EPR）研究的溶液结构和电子性质，和Mössbauer的光谱学和电化学，为了详细了解解的结构和相对稳定性，对它们进行了详细讨论。特别地，对于配体之一，杂价铁通过Fe II 2前体的化学氧化，可以生产III Fe II物种。报道了复合物，特别是杂价复合物的磷酸酶反应性。这些研究包括pH依赖型和底物浓度依赖型研究，从
• Selective Coordination of Gallium(III), Zinc(II), and Copper(II) by an Asymmetric Dinucleating Ligand: A Model for Metallophosphatases
  作者：Simone Bosch、Peter Comba、Lawrence R. Gahan、Graeme R. Hanson、Christopher Noble、Gerhard Schenk、Hubert Wadepohl

  DOI：10.1002/chem.201503348

  日期：2015.12.7

  of H3L with the three metal ions in solution was monitored by NMR spectroscopy or EPR and UV/Vis/near‐IR spectroscopy, as well as by ESI‐MS to analyze the selectivity of the two metal‐ion sites A and B of this model ligand for metallophosphatases; the spectroscopic assignments are supported by X‐ray crystallography results. The first ZnII ion coordinates to site A with unsubstituted pyridine donors

  双核配体H 3 L（H 3 L = 2-[双（吡啶-2-基甲基）氨基]甲基} -6-[双（6-吡咯并戊基吡啶并-2-基甲基）氨基]甲基}-的络合研究4-甲基苯酚），具有金属结合位点A和B，它们都为金属离子提供四个供体；叔胺; 据报道，有两个吡啶（在位点B被酰胺氢键供体取代）和与Zn II，Cu II和Ga III桥接的酚盐。H 3的滴定通过NMR光谱法或EPR和UV / Vis / Near-IR光谱法以及ESI-MS监测溶液中具有三种金属离子的L，以分析该模型配体的两个金属离子位点A和B的选择性用于金属磷酸酶；X射线晶体学结果支持光谱分配。第一个Zn II离子与未取代的吡啶供体一起配位到位点A，在加入第二当量的Zn II时，它与空间上难以接近的位点B配位。从类似的Ga III滴定中可以看出，只有单核络合物当Ga III中心与位点A配位时，就获得了。当一当量的Ga III与单核Zn反应时II型配合物，Zn