Answering important biological and chemical questions

The key factors involved during ageing are linked to increased cellular reactive oxygen species (ROS), within skin providing a suitable model following exposure to ultraviolet radiation (UVR) in sunlight. Antioxidants applied either topically or in the diet have been shown to protect the skin against ROS production resulting in oxidative stress. We, and others, have previously shown that mitochondria, the batteries or powerhouse of the cell are the major site of ROS production in the cell. Importantly in this respect, we have shown for the first time that a mitochondria-localised antioxidant, Tiron, a potent ROS scavenger, can permeate the mitochondrial membrane and confer complete (100%) protection against both UVR and hydrogen peroxide (chemical oxidative stressor) induced mitochondrial DNA damage in human skin. No other active has been published that is superior to the protection afforded by Tiron as demonstrated in this study.
 
Tiron is a well-known mitochondria-targeted iron chelator with promising potential for ROS protection, however, exploitation of this material is difficult as it is in the public domain. As a result, we have been able to develop new small molecule analogues of Tiron that confer the superior ROS protection of the mitochondria which has led to us engaging Croda International to explore this property. Biochemical screening of the Tiron analogues by Croda using their proprietary technology has confirmed the results we obtained here at Newcastle University, showing that the Tiron analogues are superior ROS protectants. However, during the development of the compound at Croda, it became apparent that the molecules physicochemical properties prevented them from being formulated into products, particularly in water-soluble formulations.
 
Consequently, the project aims to generate a new series of analogues (based on the existing architecture) to adjust the physicochemical properties and make the molecules more water soluble whilst maintaining their biological activity. Success in this objective would mean that Croda could license this technology from Newcastle University for incorporation into future products in the skincare industry.