Co( ii ) complexes of tetraazamacrocycles appended with amide or hydroxypropyl groups as paraCEST agents
Co( ii ) complexes of tetraazamacrocycles appended with amide or hydroxypropyl groups as paraCEST agents
复制标题
带有酰胺或羟丙基的四氮杂大环Co(ii)配合物作为对位CEST试剂
DOI：
10.1039/d3dt01572f
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发表时间：
2023
影响因子：
4
通讯作者：
Morrow, Janet R.
中科院分区：
文献类型：
--
作者：
Raymond, Jaclyn J.;Abozeid, Samira M.;Sokolow, Gregory E.;Bond, Christopher J.;Yap, Constance E.;Nazarenko, Alexander Y.;Morrow, Janet R.
研究了1，4，7，10-四氮杂环十二烷（CYCLEN）或1，4，8，11-四氮杂环十四烷（CYCLAM）与2-羟丙基或氨基甲酰基甲基（酰胺）侧基的Co（II）配合物，目的是开发顺磁性化学交换饱和转移（paraCEST）试剂。单晶X-射线衍射研究表明，两个与六齿配体的配位阳离子，[Co（DHP）]2+和[Co（BABC）]2+，形成六配位配合物;而两个基于CYCLEN的与潜在的八齿配体的配合物，[Co（THP）]2+和[Co（HPAC）]2+，是七配位的，四个侧基中只有三个与金属中心结合。这些配合物的1H NMR谱表明，六配位配合物在水溶液中作为单一的异构体存在。对于固态的七配位配合物，在水溶液中的NMR时间尺度上（[Co（HPAC）]2+）是高度流动的，而[Co（THP）]2+的NMR谱与所有侧基结合的八配位配合物一致。钴（II）复合物的CYCLEN衍生物显示CEST效应的低强度，被分配到NH或OH基团的悬垂。一种络合物[Co（DHP）]2+在113 ppm处相对于本体水显示出高度移位的CEST峰，这归因于OH质子。然而，CEST效应是最大的两个钴（II）CYCLAM为基础的配合物与协调的酰胺基团进行NH质子交换。所有五个配合物是惰性的解离在缓冲溶液中含有碳酸盐和磷酸盐，并对trans-metalation过量的锌（II）。这些数据提供了深入了解生产的强烈CEST效应的四氮杂大环配合物与侧基含有NH或OH可交换的质子。基于CYCLAM的复合物的强烈和高度移位的CEST峰表明它们有希望作为paraCEST试剂进一步开发。
Co(II) complexes of 1,4,7,10-tetraazacyclododecane (CYCLEN) or 1,4,8,11-tetraazacyclotetradecane (CYCLAM) with 2-hydroxypropyl or carbamoylmethyl (amide) pendants are studied with the goal of developing paramagnetic chemical exchange saturation transfer (paraCEST) agents. Single-crystal X-ray diffraction studies show that two of the coordination cations with hexadentate ligands, [Co(DHP)]2+ and [Co(BABC)]2+, form six-coordinate complexes; whereas two CYCLEN-based complexes with potentially octadentate ligands, [Co(THP)]2+ and [Co(HPAC)]2+, are seven-coordinate with only three of the four pendant groups bound to the metal center. 1H NMR spectra of these complexes suggest that the six-coordinate complexes are present as a single isomer in aqueous solution. For the complexes which are seven-coordinate in the solid state, one is highly fluxional in aqueous solution on the NMR time scale ([Co(HPAC)]2+), whereas the NMR spectrum of [Co(THP)]2+ is consistent with an eight-coordinate complex with all pendants bound. Co(II) complexes of CYCLEN derivatives show CEST effects of low intensity that are assigned to NH or OH groups of the pendants. One complex, [Co(DHP)]2+, shows a highly-shifted CEST peak at 113 ppm versus bulk water, attributed to OH protons. However, the CEST effect is largest for two Co(II) CYCLAM-based complexes with coordinated amide groups that undergo NH proton exchange. All five complexes are inert towards dissociation in buffered solutions containing carbonate and phosphate and towards trans-metalation by excess Zn(II). These data give insight into the production of an intense CEST effect for tetraazamacrocyclic complexes with pendant groups containing NH or OH exchangeable protons. The intense and highly shifted CEST peak(s) of the CYCLAM-based complexes suggest that they are promising for further development as paraCEST agents.