Xia Shijing, Villamena Frederick A, Hadad Christopher M, Kuppusamy Periannan, Li Yunbo, Zhu Hong, Zweier Jay L
Department of Chemistry, The Ohio State University, Columbus, Ohio 43210, USA.
J Org Chem. 2006 Sep 15;71(19):7268-79. doi: 10.1021/jo0610560.
Tetrathiatriarylmethyl (TAM) radicals are commonly used as oximetry probes for electron paramagnetic resonance imaging applications. In this study, the electronic properties and the thermodynamic preferences for O2 addition to various TAM-type triarylmethyl (trityl) radicals were theoretically investigated. The radicals' stability in the presence of O2 and biological milieu was also experimentally assessed using EPR spectroscopy. Results show that H substitution on the aromatic ring affects the trityl radical's stability (tricarboxylate salt 1-CO2Na > triester 1-CO2Et > diester 2-CO2Et > monoester 3-CO2Et) and may lead to substitution reactions in cellular systems. We propose that this degradation process involves an arylperoxyl radical that can further decompose to alcohol or quinone products. This study demonstrates how computational chemistry can be used as a tool to rationalize radical stability in the redox environment of biological systems and aid in the future design of more biostable trityl radicals.
四硫代三芳基甲基（TAM）自由基通常用作电子顺磁共振成像应用中的血氧测定探针。在本研究中，从理论上研究了各种TAM型三芳基甲基（三苯甲基）自由基的电子性质以及与O2加成的热力学偏好。还使用电子顺磁共振光谱对自由基在O2和生物环境存在下的稳定性进行了实验评估。结果表明，芳环上的H取代会影响三苯甲基自由基的稳定性（三羧酸盐1-CO2Na > 三酯1-CO2Et > 二酯2-CO2Et > 单酯3-CO2Et），并可能导致细胞系统中的取代反应。我们提出，这种降解过程涉及一种芳基过氧自由基，它可以进一步分解为醇或醌产物。这项研究展示了计算化学如何作为一种工具来合理化生物系统氧化还原环境中自由基的稳定性，并有助于未来设计更具生物稳定性的三苯甲基自由基。
