Frank Juliane, Elewa Marwa, Said Mohamed M, El Shihawy Hosam A, El-Sadek Mohamed, Müller Diana, Meister Annette, Hause Gerd, Drescher Simon, Metz Hendrik, Imming Peter, Mäder Karsten
†Institut für Pharmazie, Martin-Luther-Universität (MLU) Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany.
‡Faculty of Pharmacy, Suez Canal University, P.O. 41522, Ismailia, Egypt.
J Org Chem. 2015 Jul 2;80(13):6754-66. doi: 10.1021/acs.joc.5b00918. Epub 2015 Jun 12.
Tissue oxygenation plays an important role in the pathophysiology of various diseases and is often a marker of prognosis and therapeutic response. EPR (ESR) is a suitable noninvasive oximetry technique. However, to reliably deploy soluble EPR probes as oxygen sensors in complex biological systems, there is still a need to investigate and improve their specificity, sensitivity, and stability. We reproducibly synthesized various derivatives of tetrathiatriarylmethyl and tetrachlorotriarylmethyl (trityl) radicals. Hydrophilic radicals were investigated in aqueous solution mimicking physiological conditions by, e.g., variation of viscosity and ionic strength. Their specificity was satisfactory, but the oxygen sensitivity was low. To enhance the capability of trityl radicals as oxygen sensors, encapsulation into oily core nanocapsules was performed. Thus, different lipophilic triesters were prepared and characterized in oily solution employing oils typically used in drug formulations, i.e., middle-chain triglycerides and isopropyl myristate. Our screening identified the deuterated ethyl ester of D-TAM (radical 13) to be suitable. It had an extremely narrow single EPR line under anoxic conditions and excellent oxygen sensitivity. After encapsulation, it retained its oxygen responsiveness and was protected against reduction by ascorbic acid. These biocompatible and highly sensitive nanosensors offer great potential for future EPR oximetry applications in preclinical research.
组织氧合作用在多种疾病的病理生理学中发挥着重要作用，并且常常是预后和治疗反应的一个指标。电子顺磁共振（EPR，即电子自旋共振，ESR）是一种合适的非侵入性血氧测定技术。然而，为了在复杂生物系统中可靠地将可溶性EPR探针用作氧传感器，仍有必要研究并提高它们的特异性、灵敏度和稳定性。我们可重复地合成了四硫代三芳基甲基和四氯三芳基甲基（三苯甲基）自由基的各种衍生物。通过例如改变粘度和离子强度，在模拟生理条件的水溶液中对亲水性自由基进行了研究。它们的特异性令人满意，但氧灵敏度较低。为了增强三苯甲基自由基作为氧传感器的能力，我们将其封装到油核纳米胶囊中。因此，制备了不同的亲脂性三酯，并在使用药物制剂中常用的油（即中链甘油三酯和肉豆蔻酸异丙酯）的油溶液中对其进行了表征。我们的筛选确定D - TAM的氘代乙酯（自由基13）是合适的。它在缺氧条件下具有极窄的单一EPR谱线，并且氧灵敏度极佳。封装后，它保留了对氧的响应性，并受到抗坏血酸还原的保护。这些生物相容性高且灵敏度高的纳米传感器在临床前研究的未来EPR血氧测定应用中具有巨大潜力。
