Inner-Sphere and Outer-Sphere Water Interactions in Co(II) paraCEST Agents
Inner-Sphere and Outer-Sphere Water Interactions in Co(II) paraCEST Agents
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DOI：
10.1021/acs.inorgchem.7b02977
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发表时间：
2018-02-19
影响因子：
4.6
通讯作者：
Morrow, Janet R.
中科院分区：
文献类型：
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作者：
Abozeid, Samira M.;Snyder, Eric M.;Morrow, Janet R.
高自旋Co（II）配合物作为paraCEST试剂（paraCEST =顺磁化学交换饱和转移）用于磁共振成像应用是有希望的。这里介绍了具有结合水配体的Co（II）paraCEST试剂的第一个例子。合成了4个以1，4，7-三氮杂环壬烷为配体的含醇或酰胺侧基的Co（II）大环配合物。两个大环包封的Co（II）和不含水的配位体，如X-射线晶体学研究所示，和两个配合物具有大环只有五个配体供体基团，留下一个开放的配位位点结合水。使用pH电位法，其特征在于在复合物中的醇，水或酰胺基团的电离。这些数据表明，其中一个复合物具有pK（a）接近6的容易去质子化的基团，其被指定为醇侧基。酰胺侧基在高pH（>8）下去质子化，并且Co（II）络合物的水配体在中性pH下不去质子化。所有络合物通过醇OH或酰胺NH质子交换产生CEST峰。水配位体交换太快而不能产生CEST效应，如变温O-17 NMR光谱研究所示。与内球水配体的可用的配位位点的配合物产生大的顺磁位移和加宽的O-17共振的散装水，而封装的配合物显示出少得多的移动和加宽的O-17共振。所有的配合物产生大量的顺磁位移的H-1共振的散装水，这是有前途的超分子CEST剂的发展。
High-spin Co(II) complexes are promising for development as paraCEST agents (paraCEST = paramagnetic chemical exchange saturation transfer) for magnetic resonance imaging applications. The first examples of Co(II) paraCEST agents with bound water ligands are presented here. Four Co(II) macrocyclic complexes based on 1,4,7-triazacyclononane and containing either pendent alcohol or pendent amide groups were prepared. Two of the macrocycles encapsulate the Co(II) and contain no water ligands as shown by X-ray crystallographic studies, and two complexes have macrocycles with only five ligand donor groups to leave an open coordination site for bound water. The ionization of alcohol, water, or amide groups in the complexes was characterized by using pH potentiometry. These data show that one of the complexes has a readily deprotonated group with a pK(a) close to 6, which is assigned as an alcohol pendent. Amide pendents deprotonate at high pH (>8), and the water ligands of the Co(II) complexes are not deprotonated at neutral pH. All complexes produce CEST peaks through either alcohol OH or amide NH proton exchange. The water ligands exchange too rapidly to produce a CEST effect as shown by variable -temperature O-17 NMR spectroscopy studies. The complexes with available coordination sites for inner-sphere water ligands produce large paramagnetic shifts and broadening of the O-17 resonances of bulk water, whereas the encapsulated complexes show much less shifting and broadening of O-17 resonances. All complexes produce substantial paramagnetic shifts of the H-1 resonances of bulk water, which is promising for the development of supramolecular CEST agents.