title: Synthesis, Characterization, and Nanoencapsulation of Tetrathiatriarylmethyl and Tetrachlorotriarylmethyl (Trityl) Radical Derivatives—A Study To Advance Their Applicability as in Vivo EPR Oxygen Sensors.
abstract: 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.
authors.affiliation: †Institut für Pharmazie, Martin-Luther-Universität (MLU) Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Frank
authors.affiliation: †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.
authors.forename: Marwa
authors.initials: M
authors.lastname: Elewa
authors.affiliation: ‡Faculty of Pharmacy, Suez Canal University, P.O. 41522, Ismailia, Egypt.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Said
authors.affiliation: ‡Faculty of Pharmacy, Suez Canal University, P.O. 41522, Ismailia, Egypt.
authors.forename: Hosam A
authors.initials: HA
authors.lastname: El Shihawy
authors.affiliation: ∥Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Sadek
authors.affiliation: †Institut für Pharmazie, Martin-Luther-Universität (MLU) Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Müller
authors.affiliation: ⊥Center for Structure and Dynamics of Proteins (MZP), Biocenter Martin-Luther-Universität (MLU) Halle-Wittenberg, Weinbergweg 22, 06120 Halle (Saale), Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Meister
authors.affiliation: #Biocenter Martin-Luther-Universität (MLU) Halle-Wittenberg, Weinbergweg 22, 06120 Halle (Saale), Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Hause
authors.affiliation: †Institut für Pharmazie, Martin-Luther-Universität (MLU) Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Drescher
authors.affiliation: †Institut für Pharmazie, Martin-Luther-Universität (MLU) Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Metz
authors.affiliation: †Institut für Pharmazie, Martin-Luther-Universität (MLU) Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Imming
authors.affiliation: †Institut für Pharmazie, Martin-Luther-Universität (MLU) Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Mäder
mesh_terms: D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D005609:Free Radicals / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D015394:Molecular Structure; D010092:Oximetry; D010100:Oxygen / Q000737:chemistry*; D014320:Triphenylmethyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D005609:Free Radicals; D014320:Triphenylmethyl Compounds; D010100:Oxygen