Timothy Johnstone

2020 Hellman Fellow

johnstone@ucsc.edu

Assistant Professor; Chemistry & Biochemistry
UC Santa Cruz

Project Title: Medicinal Inorganic Chemistry to Treat Carbon Monoxide Poisoning and Neglected Tropical Disease

Project Description: The Hellman Fellowship will be used to support the Johnstone Lab’s work towards developing an antidote for carbon monoxide poisoning and understanding the functioning of antimony-based drugs used to treat a neglected tropical disease called leishmaniasis. Despite the fact that it is one of the most common forms of poisoning, there is no established antidote for CO poisoning. Our goal is to ultimately develop a convenient and rapid-acting antidote. By exploiting our understanding of the chemistry of CO and the nature of its interaction with metals, we have successfully designed small molecules that can bind CO more strongly than hemoglobin and we are optimizing this binding. Leishmaniasis is a disease caused by infection with parasites from the genus Leishmania. It belongs to the class of illnesses called Neglected Tropical Diseases. These diseases primarily affect individuals in low- and middle-income countries and do not receive significant attention from the mainstream pharmaceutical industry. Two of the drugs used to treat this disease contain antimony: meglumine antimoniate and sodium stibogluconate. Despite being administered to hundreds of thousands of people each year, the molecular structures of the pentavalent antimonials remain unknown. We will use physical inorganic methods to ascertain the structures of these drugs and then use that information to probe their mechanism of action.