用于生物医学电子顺磁共振应用和成像的持久性三苯甲基自由基的大规模合成。
Large-scale synthesis of a persistent trityl radical for use in biomedical EPR applications and imaging.
作者信息
Dhimitruka Ilirian, Velayutham Murugesan, Bobko Andrey A, Khramtsov Valery V, Villamena Frederick A, Hadad Christopher M, Zweier Jay L
机构信息
Center for Biomedical EPR Spectroscopy and Imaging, The Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
出版信息
Bioorg Med Chem Lett. 2007 Dec 15;17(24):6801-5. doi: 10.1016/j.bmcl.2007.10.030. Epub 2007 Oct 17.
Abstract
Tetrathiatriarylmethyl radicals are ideal spin probes for biological electron paramagnetic resonance (EPR) spectroscopy and imaging. The wide application of trityl radicals as biosensors of oxygen or other biological radicals was hampered by the lack of affordable large-scale syntheses. We report the large-scale synthesis of the Finland trityl radical using an improved addition protocol of the aryl lithium monomer to methylchloroformate. A new reaction for the formal one-electron reduction of trityl alcohols to trityl radicals using neat trifluoroacetic acid is reported as well. Initial applications show that the compound is very sensitive to molecular oxygen. It has already provided high-resolution EPR images on large aqueous samples and should be suitable for a broad range of in vivo applications.
摘要
四硫代三芳基甲基自由基是用于生物电子顺磁共振（EPR）光谱学和成像的理想自旋探针。由于缺乏经济实惠的大规模合成方法，三芳基甲基自由基作为氧气或其他生物自由基的生物传感器的广泛应用受到了阻碍。我们报告了使用改进的芳基锂单体与氯甲酸甲酯的加成方案大规模合成芬兰三芳基甲基自由基。还报道了一种使用纯三氟乙酸将三芳基甲醇正式单电子还原为三芳基甲基自由基的新反应。初步应用表明，该化合物对分子氧非常敏感。它已经在大型水性样品上提供了高分辨率的EPR图像，应该适用于广泛的体内应用。
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本文引用的文献
1
Trityl radicals as persistent dual function pH and oxygen probes for in vivo electron paramagnetic resonance spectroscopy and imaging: concept and experiment.
J Am Chem Soc. 2007 Jun 13;129(23):7240-1. doi: 10.1021/ja071515u. Epub 2007 May 19.
2
Fast 3D spatial EPR imaging using spiral magnetic field gradient.
J Magn Reson. 2007 Apr;185(2):283-90. doi: 10.1016/j.jmr.2007.01.001. Epub 2007 Jan 8.
3
Reactivity of molecular oxygen with ethoxycarbonyl derivatives of tetrathiatriarylmethyl radicals.
J Org Chem. 2006 Sep 15;71(19):7268-79. doi: 10.1021/jo0610560.
4
Electron paramagnetic resonance oxygen images correlate spatially and quantitatively with Oxylite oxygen measurements.
Clin Cancer Res. 2006 Jul 15;12(14 Pt 1):4209-17. doi: 10.1158/1078-0432.CCR-05-0446.
5
The role of oxidants and free radicals in reperfusion injury.
Cardiovasc Res. 2006 May 1;70(2):181-90. doi: 10.1016/j.cardiores.2006.02.025. Epub 2006 Mar 3.
6
Monitoring drug delivery processes by EPR and related techniques--principles and applications.
Adv Drug Deliv Rev. 2005 Jun 15;57(8):1171-90. doi: 10.1016/j.addr.2005.01.023. Epub 2005 Apr 15.
7
Application of in vivo EPR in brain research: monitoring tissue oxygenation, blood flow, and oxidative stress.
NMR Biomed. 2004 Aug;17(5):327-34. doi: 10.1002/nbm.899.
8
Cardiac applications of EPR imaging.
NMR Biomed. 2004 Aug;17(5):226-39. doi: 10.1002/nbm.912.
9
In vivo measurement and mapping of skin redox stress induced by ultraviolet light exposure.
Free Radic Biol Med. 2004 Mar 1;36(5):665-72. doi: 10.1016/j.freeradbiomed.2003.11.024.
10
Quantitative tumor oxymetric images from 4D electron paramagnetic resonance imaging (EPRI): methodology and comparison with blood oxygen level-dependent (BOLD) MRI.
Magn Reson Med. 2003 Apr;49(4):682-91. doi: 10.1002/mrm.10408.
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