Caldwell Michael A, Brue Christopher R, Whittemore Tyler J, Meade Thomas J
Departments of Chemistry, Molecular Biosciences, Neurobiology, and Radiology, Northwestern University, Evanston, IL, 60208.
RSC Adv. 2020;10(15):8994-8999. doi: 10.1039/c9ra11058e. Epub 2020 Mar 3.
Differences in tissue pH can be diagnostic of cancer and other conditions that shift cell metabolism. Paramagnetic probes are promising tools for pH mapping in vivo using magnetic resonance spectroscopy (MRS) as they provide uniquely shifted MR signals that change with pH. Here, we demonstrate a 3-hydroxy-6-methylpyridyl coordinating group as a new pH-responsive reporter group for Ln(III) MRS probes. The pH response of the complex was observed by UV-Vis, fluorescence, and NMR spectroscopies, and modeled using DFT. These results provide insight into the observed pH-dependent NMR spectrum of the complex. The protonation state of the hydroxypyridine changes the coordinating ability of the ligand, affecting the dipolar field of the lanthanide and the chemical shift of nearby reporter nuclei. The favorable pH response and coordination properties of the 3-hydroxypyridyl group indicates its potential for further development as a dual responsive-reporter group. Incorporation into optimized scaffolds for MRS detection may enable sensitive pH-mapping .
组织pH值的差异可用于诊断癌症及其他改变细胞代谢的病症。顺磁探针是利用磁共振波谱（MRS）在体内进行pH测绘的有前景的工具，因为它们能提供随pH变化而独特偏移的MR信号。在此，我们展示了一种3-羟基-6-甲基吡啶配位基团作为用于Ln(III) MRS探针的新型pH响应报告基团。通过紫外可见光谱、荧光光谱和核磁共振光谱观察了该配合物的pH响应，并使用密度泛函理论（DFT）进行建模。这些结果为所观察到的配合物pH依赖型核磁共振谱提供了见解。羟基吡啶的质子化状态改变了配体的配位能力，影响了镧系元素的偶极场和附近报告核的化学位移。3-羟基吡啶基团良好的pH响应和配位性质表明其作为双响应报告基团具有进一步开发的潜力。将其纳入用于MRS检测的优化支架中可能实现灵敏的pH测绘。
