1-methylphosphonic acid-4,7-bis((6-pyridin-2-yl)methyl)-1,4,7-triazacyclononane | 1195287-28-5

• 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: 1-methylphosphonic acid-4,7-bis((6-pyridin-2-yl)methyl)-1,4,7-triazacyclononane
• 英文别名: H4pbpatcn；6-[[4-[(6-Carboxypyridin-2-yl)methyl]-7-(phosphonomethyl)-1,4,7-triazonan-1-yl]methyl]pyridine-2-carboxylic acid；6-[[4-[(6-carboxypyridin-2-yl)methyl]-7-(phosphonomethyl)-1,4,7-triazonan-1-yl]methyl]pyridine-2-carboxylic acid
• CAS: 1195287-28-5
• 化学式: C₂₁H₂₈N₅O₇P
• 分子量: 493.456
• InChiKey: DPYRYSWXQAYILH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.5
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  174
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  1-methylphosphonic acid-4,7-bis((6-pyridin-2-yl)methyl)-1,4,7-triazacyclononane 、 europium(III) trifluoromethanesulfonate 在 KOD 作用下， 以 重水 为溶剂， 生成 Eu(1-methylphosphonic acid-4,7-bis((6-carboxypyridine-2-yl)methyl)-1,4,7-triazacylcononane(4-))
  参考文献：
  名称：

  Gadolinium(III) complexes of 1,4,7-triazacyclononane based picolinate ligands: simultaneous optimization of water exchange kinetics and electronic relaxation

  摘要：

  以 1,4,7-三氮杂环壬烷锚为基础，制备了两种新的三元皮啶酸盐 H3ebpatcn（1-羧乙基-4,7-双((6-羧基吡啶-2-基)甲基)-1,4,7-三氮杂环壬烷）和 H4pbpatcn（1-甲基膦酸-4,7-双((6-羧基吡啶-2-基)甲基)-1、和 H4pbpatcn（1-甲基膦酸-4,7-双((6-羧基吡啶-2-基)甲基)-1,4,7-三氮杂环壬烷）配体，并通过核磁共振、荧光和电位研究对其镧系配合物进行了表征。在 45 MHz 和 298 K 条件下，[Gd(ebpatcn)(H2O)] 复合物的弛豫度为 r1 = 4.68 mM-1 s-1，而在相同条件下，[Gd(Hpbpatcn)(H2O)] 复合物的弛豫度为 r1 = 4.55 mM-1 s-1。与之前报道的 H3bpatcn（1-(羧甲基)-4,7-双[(6-羧基吡啶-2-基)甲基]-1,4,7-三氮杂环壬烷）相比，配体的支架发生了改变，从而优化了这些钆配合物的性质。用丙酸基团（H3ebpatcn）或膦酸基团（H4pbpatcn）取代 H3bpatcn 配体的乙酸结合基团，可加快这两种单砷钆络合物中配位水分子的交换速率。根据 O17 NMRD 测量，[Gd(Hpbpatcn)(H2O)] 的水交换率 kex = 34 × 106 s-1，处于 SBM 理论预测的最佳值（30 至 50）×106 s-1 范围内，从而优化了未来高弛豫性大分子钆基造影剂的设计。复合物[Gd(ebpatcn)(H2O)]的水交换速率 kex298 = 86 × 106 s-1 是文献中报道的仅有一个内球水分子的中性复合物中最快的。这些改性钆配合物具有相对较高的稳定性（Gd(pbpatcn) 的 pGd = 14.1，Gd(ebpatcn) 的 pGd = 13.1），与[Gd(bpatcn)(H2O)]配合物的 pGd = 13.6 相似。铽配合物也保持了较高的发光效率。然而，虽然[Gd(ebpatcn)(H2O)]的纵向电子自旋弛豫时间保持在一定值，足以不影响大分子复合物的弛豫性（瞬态 ZFS 振幅 Δ2 [1020 rad2 s-2] = 0.39），但 O17 驰豫和 1H NMRD 表明含膦酸盐复合物的电子自旋弛豫相当快（Δ2 [1020 rad2 s-2]= 1.3）。

  DOI：

  10.1039/b907738c

文献信息

• Gadolinium(III) complexes of 1,4,7-triazacyclononane based picolinate ligands: simultaneous optimization of water exchange kinetics and electronic relaxation
  作者：Aline Nonat、Marion Giraud、Christelle Gateau、Pascal H. Fries、Lothar Helm、Marinella Mazzanti

  DOI：10.1039/b907738c

  日期：——

  The two new tripodal picolinate H3ebpatcn (1-carboxyethyl-4,7-bis((6-carboxypyridin-2-yl)methyl)-1,4,7-triazacyclononane) and H4pbpatcn (1-methylphosphonic-acid-4,7-bis((6-carboxypyridin-2-yl)methyl)-1,4,7-triazacyclononane) ligands based on the 1,4,7-triazacyclononane anchor were prepared and their lanthanide complexes were characterized by NMR, fluorescence and potentiometric studies. The [Gd(ebpatcn)(H2O)] complex displays a relaxivity of r1 = 4.68 mM−1 s−1 at 45 MHz and 298 K, whereas r1 = 4.55 mM−1 s−1 was measured for [Gd(Hpbpatcn)(H2O)] under the same conditions. The modified scaffold of the ligands with respect to the previously reported H3bpatcn (1-(carboxymethyl)-4,7-bis[(6-carboxypyridin-2-yl)methyl]-1,4,7-triazacyclononane) leads to an optimization of the properties of these gadolinium complexes. The replacement of an acetate binding group of the H3bpatcn ligand with a propionate group (H3ebpatcn) or a phosphonate group (H4pbpatcn) leads to a faster exchange rate of the coordinated water molecule in both mono-aquo gadolinium complexes. The resulting water exchange rate is optimized for the future design of high relaxivity macromolecular gadolinium based contrast agents with a value measured by O17 NMRD of kex = 34 × 106 s−1 for [Gd(Hpbpatcn)(H2O)] falling in the range of optimum values of (30 to 50) × 106 s−1 predicted by the SBM theory. The water exchange rate kex298 = 86 × 106 s−1 of the complex [Gd(ebpatcn)(H2O)] is the fastest reported in the literature for a neutral complex with only one inner-sphere water molecule. The relatively high stability of these modified gadolinium complexes (pGd = 14.1 for Gd(pbpatcn) and 13.1 for Gd(ebpatcn)) is similar to that of the [Gd(bpatcn)(H2O)] complex (pGd = 13.6). The high luminescence efficiency is also retained for the terbium complex. However, whereas the longitudinal electronic spin relaxation time keeps a value for [Gd(ebpatcn)(H2O)], which is long enough not to affect the relaxivity in macromolecular complexes (transient ZFS amplitude Δ2 [1020 rad2 s−2] = 0.39), the O17 relaxation and the 1H NMRD indicate a rather fast electron spin relaxation for the phosphonate containing complex (Δ2 [1020 rad2 s−2]= 1.3).

  以 1,4,7-三氮杂环壬烷锚为基础，制备了两种新的三元皮啶酸盐 H3ebpatcn（1-羧乙基-4,7-双((6-羧基吡啶-2-基)甲基)-1,4,7-三氮杂环壬烷）和 H4pbpatcn（1-甲基膦酸-4,7-双((6-羧基吡啶-2-基)甲基)-1、和 H4pbpatcn（1-甲基膦酸-4,7-双((6-羧基吡啶-2-基)甲基)-1,4,7-三氮杂环壬烷）配体，并通过核磁共振、荧光和电位研究对其镧系配合物进行了表征。在 45 MHz 和 298 K 条件下，[Gd(ebpatcn)(H2O)] 复合物的弛豫度为 r1 = 4.68 mM-1 s-1，而在相同条件下，[Gd(Hpbpatcn)(H2O)] 复合物的弛豫度为 r1 = 4.55 mM-1 s-1。与之前报道的 H3bpatcn（1-(羧甲基)-4,7-双[(6-羧基吡啶-2-基)甲基]-1,4,7-三氮杂环壬烷）相比，配体的支架发生了改变，从而优化了这些钆配合物的性质。用丙酸基团（H3ebpatcn）或膦酸基团（H4pbpatcn）取代 H3bpatcn 配体的乙酸结合基团，可加快这两种单砷钆络合物中配位水分子的交换速率。根据 O17 NMRD 测量，[Gd(Hpbpatcn)(H2O)] 的水交换率 kex = 34 × 106 s-1，处于 SBM 理论预测的最佳值（30 至 50）×106 s-1 范围内，从而优化了未来高弛豫性大分子钆基造影剂的设计。复合物[Gd(ebpatcn)(H2O)]的水交换速率 kex298 = 86 × 106 s-1 是文献中报道的仅有一个内球水分子的中性复合物中最快的。这些改性钆配合物具有相对较高的稳定性（Gd(pbpatcn) 的 pGd = 14.1，Gd(ebpatcn) 的 pGd = 13.1），与[Gd(bpatcn)(H2O)]配合物的 pGd = 13.6 相似。铽配合物也保持了较高的发光效率。然而，虽然[Gd(ebpatcn)(H2O)]的纵向电子自旋弛豫时间保持在一定值，足以不影响大分子复合物的弛豫性（瞬态 ZFS 振幅 Δ2 [1020 rad2 s-2] = 0.39），但 O17 驰豫和 1H NMRD 表明含膦酸盐复合物的电子自旋弛豫相当快（Δ2 [1020 rad2 s-2]= 1.3）。