We Address Oxidative Stress in Your Body
by Sana Karbalaei
Nowadays, inflammatory, cardiovascular, and neurological diseases are one of the main reasons for mortality, and millions of people suffer from these illnesses around the world. High concentrations of reactive oxygen species (ROS) within the body, and resultant oxidative stress has been linked to these health disorders. However, low concentrations of ROS are required for proper cell signaling, and they help to regulate neuronal and cardiomyocyte excitability. Dr. Goldsmith’s research group is developing sensors to monitor ROS concentrations and facilitate the early diagnosis and treatment of these diseases.
Figure 1. ORTEP representation of a macrocyclic quinol-containing ligand
For one of my projects, I have designed a sensor that reacts directly with hydrogen peroxide, the most abundant ROS in our body. This sensor contains a manganese complex that was synthesized by incorporation of a macrocycle into a redox-active quinol-containing ligand (Fig. 1) that exhibits changes in their T1-derived relaxivity upon reaction with hydrogen peroxide.
During its reaction with H2O2, the quinols oxidize to para-quinones, which are subsequently displaced by H2O (Fig. 2), and the observed increase in relaxivity results from greater aquation of the manganese. Infrared (IR) spectroscopy and mass spectrometry (MS) confirmed this oxidation for quinol groups. Changes in the relaxivity can be detected by magnetic resonance imaging (MRI), which has been used extensively for non-invasively visualizing soft tissues within whole-body subjects. As a result, recognition of oxidative stress in our body should be non-invasive, efficient, and straightforward with this sensor.
Figure 2. Redox activity of metal-bound quinols
The main concern for MRI contrast agents' usage is their side effects. The toxicity of this probe was tested with H9c2 cells, and fortunately, its toxicity was found to be very low. Moreover, this agent should be highly stable within the body. Dissociation and aggregation of the metal center of this sensor in the kidney or brain is unlikely, because manganese used in the structure of this MRI sensor cannot be easily displaced by either iron or zinc, two of the most common transition-metal ions in biology. The results of this research project were recently published in the Inorganic Chemistry journal and selected as a Featured article.
Acknowledgement: This work is supported by the National Sciences Foundation and was done in the lab of Prof. Christain R. Goldsmith in the department of Chemistry and Biochemistry, Auburn University.