Liu Yangping, Villamena Frederick A, Sun Jian, Xu Yingkai, Dhimitruka Ilirian, Zweier Jay L
Center for Biomedical EPR Spectroscopy and Imaging, The Davis Heart and Lung Research Institute, the Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
J Org Chem. 2008 Feb 15;73(4):1490-7. doi: 10.1021/jo7022747. Epub 2008 Jan 18.
Electron paramagnetic resonance (EPR) spectroscopy using paramagnetic probes has been employed as an important tool for the accurate determination of oxygen (O2) concentrations in biological systems. However, paramagnetic probes are still limited by their intracellular penetrability. Various esterified trityl derivatives were synthesized and characterized, and an X-ray structure of one of the triyl radicals was determined. The ester-derivatized trityls exhibited higher sensitivity to O2 concentration compared to the trityl tricarboxylate CT-03. Cyclic voltammetry was also carried out to assess the susceptibility of the trityl radicals to oxidation and reduction. Among all of the ester-derivatized trityls studied, facile hydrolysis of the acetoxymethoxy esters to the respective carboxylate was observed using porcine liver esterase. This study demonstrates that cellular permeability of the trityl radicals can be achieved by varying the type and number of ester groups. Therefore, ester-derivatized trityl radicals show great potential as intracellular EPR oximetry probes and imaging agents.
使用顺磁探针的电子顺磁共振（EPR）光谱法已成为精确测定生物系统中氧（O₂）浓度的重要工具。然而，顺磁探针的细胞内穿透性仍然有限。合成并表征了各种酯化三苯甲基衍生物，并确定了其中一种三苯甲基自由基的X射线结构。与三苯甲基三羧酸盐CT-03相比，酯化衍生的三苯甲基对O₂浓度表现出更高的敏感性。还进行了循环伏安法以评估三苯甲基自由基的氧化和还原敏感性。在所研究的所有酯化衍生的三苯甲基中，使用猪肝酯酶观察到乙酰氧基甲酯容易水解为相应的羧酸盐。这项研究表明，通过改变酯基的类型和数量可以实现三苯甲基自由基的细胞通透性。因此，酯化衍生的三苯甲基自由基作为细胞内EPR血氧测定探针和成像剂具有巨大潜力。
