具有增强惰性和高 MRI 对比能力的多核 Mn(II) 联合

螯合不稳定性显着阻碍了基于 Mn(II) 的磁共振图像 (MRI) 造影剂的发展。在此，使用 1,4,7,10-四氮杂环十二烷-N , N ', N '', N '''-四乙酸 (DOTA) 作为螯合单元，我们表明多核 Mn(II) 联合-DOTA 螯合物是惰性比临床 Gd 造影剂 Magnevist 高 69 倍。不寻常的惰性可归因于 Mn(II) 螯合物的多重结合，这可以通过对模型化合物的一系列对照研究来说明。此外，Mn(II) 联合-DOTA 螯合物的分子纵向弛豫比单核 Mn(II) 配合物高 17-167 倍。体内动态MRI 实验进一步表明，Mn(II) 联合-DOTA 复合物可以提供比 Mn-DOTA 和 Magnevist 更显着和持久的对比度增强。我们的努力不仅证明了多核 Mn(II) 联合-DOTA 配合物是 Gd 基造影剂的优越替代品，而且还强调了螯合统一作为构建高性能 Mn(II) 的一种简单而有效的策略的重要性。 ) 为基础的造影剂。

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Multinuclear Mn(II) united-DOTA complexes with enhanced inertness and high MRI contrast ability

Chelating lability significantly hinders the development of Mn(II)-based magnetic resonance image (MRI) contrast agents. Herein, using 1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid (DOTA) as a chelating unit, we show that multinuclear Mn(II) united-DOTA chelates are of up to 69-fold higher inertness than Magnevist, a clinical Gd-based contrast agent. The unusual inertness could be ascribed to the multiplexed uniting of Mn(II) chelates, which is illustrated by a series of controlled studies on model compounds. Besides, molecular longitudinal relaxivities of Mn(II) united-DOTA chelates are 17–167 times higher than those of mononuclear Mn(II) complexes. Dynamic in vivo MRI experiments further reveal that Mn(II) united-DOTA complexes could provide more substantial and persistent contrast enhancement than both Mn-DOTA and Magnevist. Our efforts not only demonstrate that multinuclear Mn(II) united-DOTA complexes are a superior alternative to Gd-based contrast agents, but also highlight the significance of chelate unification as a simple yet powerful strategy for the construction of high-performance Mn(II)-based contrast agents.