Tuning the Kinetic Inertness of Bi(3+) Complexes: The Impact of Donor Atoms on Diaza-18-Crown-6 Ligands as Chelators for (213)Bi Targeted Alpha Therapy.
Tuning the Kinetic Inertness of Bi(3+) Complexes: The Impact of Donor Atoms on Diaza-18-Crown-6 Ligands as Chelators for (213)Bi Targeted Alpha Therapy.
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DOI：
10.1021/acs.inorgchem.1c01269
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发表时间：
2021-06-21
影响因子：
4.6
通讯作者：
Wilson JJ
中科院分区：
文献类型：
--
作者：
Fiszbein DJ;Brown V;Thiele NA;Woods JJ;Wharton L;MacMillan SN;Radchenko V;Ramogida CF;Wilson JJ
放射性核素213Bi可用于靶向α治疗（TAT），这是一种利用α粒子根除癌细胞的核医学。为了将这种放射性核素用于这种应用，需要一种双功能螯合剂（BFC）将其附着在生物靶向载体上，该载体可以选择性地将其递送到癌细胞中。在这里，我们研究了6种大环配体作为潜在的BFCs，并通过核磁共振光谱、质谱和元素分析对Bi3+配合物进行了全面表征。由于具有立体化学活性的6s2孤对，三种配合物的固体结构显示出Bi3+中心的畸变几何配位。用超过1000倍的螯合剂二乙烯三胺五乙酸（DTPA）挑战Bi3+配合物的动力学性质。最具动力学惰性的配合物含有最基本的悬垂供体。采用密度泛函理论（DFT）和分子原子量子理论（QTAIM）计算对这一趋势进行了研究，表明动力学惰性与6s2孤对立体化学活性的程度无关，而与悬垂供体之间共价的程度有关。最后，用三种最有希望的配体对213Bi （30-210 kBq）进行放射性标记研究表明，当配体浓度低至10 - 7 M时，在室温下8分钟内就能快速形成放射性标记的配合物，对应的放射化学产率为bbb80 %，从而证明了这类配体在213Bi TAT中的应用前景。研究了一系列18元大环配体对Bi3+的螯合作用。这些配体显示出对该主基团离子的良好亲和力，并被证明可以有效地标记其治疗放射性同位素213Bi。
The radionuclide 213Bi can be applied for targeted α therapy (TAT), a type of nuclear medicine that harnesses α particles to eradicate cancer cells. To use this radionuclide for this application, a bifunctional chelator (BFC) is needed to attach it to a biological targeting vector that can deliver it selectively to cancer cells. Here, we investigated six macrocyclic ligands as potential BFCs, fully characterizing the Bi3+ complexes by NMR spectroscopy, mass spectrometry, and elemental analysis. Solid-state structures of three complexes revealed distorted coordination geometries about the Bi3+ center arising from the stereochemically active 6s2 lone pair. The kinetic properties of the Bi3+ complexes were assessed by challenging them with a 1000-fold excess of the chelating agent diethylenetriaminepentaacetic acid (DTPA). The most kinetically inert complexes contained the most basic pendent donors. Density functional theory (DFT) and quantum theory of atoms in molecules (QTAIM) calculations were employed to investigate this trend, suggesting that the kinetic inertness is not correlated with the extent of the 6s2 lone pair stereochemical activity, but with the extent of covalency between pendent donors. Lastly, radiolabeling studies of 213Bi (30–210 kBq) with three of the most promising ligands showed rapid formation of the radiolabeled complexes at room temperature within 8 min for ligand concentrations as low as 10−7 M, corresponding to radiochemical yields of > 80% thereby demonstrating the promise of this ligand class for use in 213Bi TAT. A series of 18-membered macrocyclic ligands is investigated for Bi3+ chelation. These ligands show promising affinity for this main group ion and are demonstrated to effectively radiolabel its therapeutic radioisotope, 213Bi.
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影响因子：
5.1
作者：
Chiarizia, R;Horwitz, EP;Cheng, YD
通讯作者：
Cheng, YD
影响因子：
2.7
作者：
Chong, Hyun-Soon;Song, Hyun A.;Ma, Xiang
通讯作者：
Ma, Xiang
影响因子：
3.1
作者：
Egorova, B. V.;Matazova, E. V.;Kalmykov, S. N.
通讯作者：
Kalmykov, S. N.
影响因子：
4.6
作者：
Dekempeneer Y;Keyaerts M;Krasniqi A;Puttemans J;Muyldermans S;Lahoutte T;D'huyvetter M;Devoogdt N
通讯作者：
Devoogdt N
影响因子：
2.7
作者：
Chong, Hyun-Soon;Lim, Sooyoun;Lewis, Michael R.
通讯作者：
Lewis, Michael R.