Abozeid Samira M, Snyder Eric M, Tittiris Timothy Y, Steuerwald Charles M, Nazarenko Alexander Y, Morrow Janet R
Department of Chemistry, University at Buffalo, State University of New York , Amherst, New York 14260, United States.
Chemistry Department, SUNY College at Buffalo , 1300 Elmwood Avenue, Buffalo, New York 14222, United States.
Inorg Chem. 2018 Feb 19;57(4):2085-2095. doi: 10.1021/acs.inorgchem.7b02977. Epub 2018 Feb 7.
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 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 NMR spectroscopy studies. The complexes with available coordination sites for inner-sphere water ligands produce large paramagnetic shifts and broadening of the O resonances of bulk water, whereas the encapsulated complexes show much less shifting and broadening of O resonances. All complexes produce substantial paramagnetic shifts of the H resonances of bulk water, which is promising for the development of supramolecular CEST agents.
高自旋Co(II)配合物有望开发成为用于磁共振成像应用的顺磁化学交换饱和转移（paraCEST）剂。本文展示了首批带有配位水配体的Co(II) paraCEST剂实例。制备了四种基于1,4,7-三氮杂环壬烷且含有侧链醇或侧链酰胺基团的Co(II)大环配合物。X射线晶体学研究表明，其中两个大环包裹着Co(II)且不含水配体，另外两个配合物的大环只有五个配体供体基团，从而留下一个用于配位水的开放配位位点。通过pH电位滴定法对配合物中醇、水或酰胺基团的电离进行了表征。这些数据表明，其中一种配合物有一个易于去质子化的基团，其pK值接近6，被确定为侧链醇。酰胺侧链在高pH值（>8）时去质子化，而Co(II)配合物的水配体在中性pH值下不会去质子化。所有配合物都通过醇OH或酰胺NH质子交换产生CEST峰。变温¹⁷O NMR光谱研究表明，水配体交换太快，无法产生CEST效应。具有内球水配体可用配位位点的配合物会使大量水的¹⁷O共振产生较大的顺磁位移和展宽，而被包裹的配合物对¹⁷O共振的位移和展宽则小得多。所有配合物都会使大量水的¹H共振产生显著的顺磁位移，这对于超分子CEST剂的开发很有前景。
