Synthesis, Characterization, and Nanoencapsulation of Tetrathiatriarylmethyl and Tetrachlorotriarylmethyl (Trityl) Radical Derivatives鈥擜 Study To Advance Their Applicability as in Vivo EPR Oxygen Sens
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- 作者：Juliane Frank ; Marwa Elewa ; Mohamed M. Said ; Hosam A. El Shihawy ; Mohamed El-Sadek ; Diana M眉ller ; Annette Meister ; Gerd Hause ; Simon Drescher ; Hendrik Metz ; Peter Imming ; Karsten M盲der
- 刊名：Journal of Organic Chemistry
- 出版年：2015
- 出版时间：July 2, 2015
- 年：2015
- 卷：80
- 期：13
- 页码：6754-6766
- 全文大小：592K
- ISSN：1520-6904
文摘
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.