Seven-coordinate Co(II), Fe(II) and six-coordinate Ni(II) amide-appended macrocyclic complexes as ParaCEST agents in biological media.
Seven-coordinate Co(II), Fe(II) and six-coordinate Ni(II) amide-appended macrocyclic complexes as ParaCEST agents in biological media.
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七配位 Co(II)、Fe(II) 和六配位 Ni(II) 酰胺附加大环配合物作为生物介质中的 ParaCEST 试剂。
DOI：
10.1021/ic5006083
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发表时间：
2014
影响因子：
4.6
通讯作者：
Morrow,JanetR
中科院分区：
文献类型：
--
作者：
Olatunde,AbiolaO;Cox,JordanM;Daddario,MichaelD;Spernyak,JosephA;Benedict,JasonB;Morrow,JanetR
报道了7，13-双（氨甲酰基甲基）-1，4，10-三氧杂-7，13-二氮杂环十五烷（L）的CoII、FeII和NiII络合物的溶液化学和固态结构，作为一类新的含有过渡金属离子的顺磁性化学交换饱和转移（paraCEST）MRI造影剂的成员。晶体学数据表明，大环配体中的氮、氧供体原子与金属离子配位生成了[Co（L）] Cl 2·2 H2O或[Fe（L）]（CF 3SO 3）2的畸变五角双锥构型配合物.配合物[Ni（L）]（CF_3SO_3）_2·H_2O具有六齿的畸变八面体构型。所有三个配合物的质子NMR谱显示高度分散和相对尖锐的质子共振。通过监测它们在生物相关条件下的解离来进一步表征复合物，所述生物相关条件包括含有磷酸盐和碳酸盐、ZnCl 2或酸性条件的溶液。paraCEST试剂在20 mMN-（2-羟乙基）哌嗪-N '-乙磺酸（pH 7.4）和100 mM NaCl中的溶液在37 ℃下在11.7 T NMR光谱仪上分别显示出[Co（L）]2+、[Ni（L）]2+和[Fe（L）]2+在远离本体水的59、72和92 ppm处的高度移位和强烈的CEST峰。在4%琼脂糖凝胶（w/w）、兔血清、鸡蛋白色或缓冲溶液中报告了CEST光谱和相应的质子交换速率常数。在37 °C下在4.7T MRI扫描仪上比较缓冲液、4%琼脂糖凝胶（w/w）或兔血清中的4 mM复合物的CEST模型。观察到反应性[Ni（L）]2+的最实质性变化，其显示兔血清和鸡蛋白色中CEST对比度降低。与缓冲溶液中的CEST对比度相比，具有最小高度移位的CEST峰（[Co（L）]2+和[Ni（L）]2+）的复合物在4%琼脂糖凝胶（w/w）中显示出CEST对比度的降低，而在4%琼脂糖凝胶（w/w）中[Fe（L）]2+的CEST效应没有实质性差异。
The solution chemistry and solid-state structures of the CoII, FeII, and NiIIcomplexes of 7,13-bis(carbamoylmethyl)-1,4,10-trioxa-7,13-diazacyclopentadecane (L) are reported as members of a new class of paramagnetic chemical exchange saturation transfer (paraCEST) MRI contrast agents that contain transition metal ions. Crystallographic data show that nitrogen and oxygen donor atoms of the macrocyclic ligand coordinate to the metal ions to generate complexes with distorted pentagonal bipyramidal geometry for [Co(L)]Cl2·2H2O or [Fe(L)](CF3SO3)2. The NiIIcomplex [Ni(L)](CF3SO3)2·H2O features a hexadentate ligand in a distorted octahedral geometry. The proton NMR spectra of all three complexes show highly dispersed and relatively sharp proton resonances. The complexes were further characterized by monitoring their dissociation under biologically relevant conditions including solutions containing phosphate and carbonate, ZnCl2, or acidic conditions. Solutions of the paraCEST agents in 20 mMN-(2-hydroxyethyl)piperazine-N′-ethanesulfonic acid (pH 7.4) and 100 mM NaCl showed highly shifted and intense CEST peaks at 59, 72, and 92 ppm away from bulk water for [Co(L)]2+, [Ni(L)]2+, and [Fe(L)]2+, respectively at 37 °C on a 11.7 T NMR spectrometer. CEST spectra with corresponding rate constants for proton exchange are reported in 4% agarose gel (w/w), rabbit serum, egg white, or buffered solutions. CEST phantoms of 4 mM complex in buffer, 4% agarose gel (w/w), or rabbit serum on a 4.7 T MRI scanner at 37 °C, are compared. The most substantial change was observed for the reactive [Ni(L)]2+, which showed reduced CEST contrast in rabbit serum and egg white. The complexes with the least highly shifted CEST peaks ([Co(L)]2+and [Ni(L)]2+) showed a reduction in CEST contrast in 4% agarose gel (w/w) compared to that in buffered solutions, while the CEST effect for [Fe(L)]2+in 4% agarose gel (w/w) was not substantially different.