EPR spin probes
Diagnostics of the future: Stable organic radicals as EPR spin probes
Diagnostic techniques based on nuclear magnetic resonance (NMR) are an essential part of modern medicine. Electron spin resonance (ESR) is a related technique with well established uses in physical and chemical analysis. Research with the aim to exploit it in pharmacy and medicine faces diverse challenges, one of them being the design, synthesis, and characterisation of spin probes. They have to be long-lived, non-toxic organic radicals, yielding strong signals, with the potential to function as sensors of (patho)physiologically important parameters (eg pH, oxygen concentration). Persubstituted triphenylmethyl (= trityl) radicals could meet these requirements. Therefore, we are working on the design and synthesis of highly specialised trityls, including trityls linked to polymers like chitosan and hydroxyethyl starch.
A chemical compound is paramagnetic if it has unpaired electrons. Many free radicals are too short-lived for diagnostic purposes, especially in vivo. The first stable organic radical was triphenylmethyl, originally described by Moses Gomberg in 1900. In recent years, significant advances in knowledge and the applicability of ESR in biochemistry, medicine and pharmacy have been made. For in vivo measurements with small animals, spectrometers and imaging software were developed. They enable 'seeing' the localization of spin probe radicals in organs and body parts, and tracking their chemical surroundings, progress and degradation.
Highly substituted triarylmethyl (TAM) radicals are a new class of spin probes, some of which are characterised by remarkable stability under physiological conditions. They allow in vivo monitoring of physicochemical parameters in the tissue in which they reside or accumulate. Local oxygen content and pH of tissues play an important role in the assessment of pathophysiological processes, particularly in tumor tissues. Synthetic exogenous spin probes are diagnostically particularly attractive because of the low noise levels and thus provide a high level of analytical specificity of endogenous free radicals.
Cooperations:
Prof. Dr. Karsten Mäder, Pharmaceutical technology, Institute of Pharmacy, MLU Halle-Wittenberg [LINK]
Prof. Dr. Darius Hinderberger, Physical Chemistry - Complex self-organizing systems, Institute of Chemistry, MLU Halle-Wittenberg [LINK]
Dr. Valery V. Khramtsov, Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio, USA
Prof. Dr. Fuminori Hyodo, Bio-medical Redox Imaging Group, Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan
Prof. Dr. Marek Murias, Department of Toxicology, Poznan University of Medical Sciences, Poland
Dr. Agnieszka Boś-Liedke, NanoBioMedical Centre, Adam Mickiewicz University, Poland
Prof. Dr. Victor M. Tormyshev, N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Russia
PhD and Diploma Theses:
M. Platzer, Diploma Thesis, Halle 2012.
D. Mueller, PhD Thesis, Halle 2013.
I. Di Bonaventura, Master Thesis, Halle/L'Aquila 2014.
M. Elewa, PhD Thesis Halle, 2017.
F. Tzschökell, Master thesis, Halle 2017.
L. Lampp, PhD Thesis, Halle 2019.