Professor Loi Do from the University of Houston will present a seminar.

Catalytic Agents to Detoxify Reactive Aldehyde Species

Abstract

Although the human body has natural defenses against reactive aldehydes species (e.g., α,β-unsaturated aldehydes, α-ketoaldehydes, dialdehydes, etc.), these systems are often impaired in patients with pathological conditions such as neurodegenerative disorders, cardiovascular diseases, or cancer. Reactive aldehydes species can disrupt living systems by alkylating nucleic acids, crosslinking proteins, and consuming essential antioxidants. Although there are currently no FDA-approved treatments for aldehyde overload, most drug candidates being studied are based on small-molecule organic scavengers. These compounds typically feature nucleophilic moieties that react with aldehydes in a stoichiometric manner, which means that a constant supply of the drugs must be provided to maintain their therapeutic effects. Because stoichiometric drugs are inefficient, our laboratory aims to develop catalytic drugs that can amplify intracellular processes to neutralize disease-causing agents. Toward this goal, we have recently identified a family of organoiridium complexes that promote transfer hydrogenation between carbonyl acceptors and hydride donors such as sodium formate or reduced nicotinamide adenine dinucleotide. We show in this presentation that our organoiridium complexes mimic reductase enzymes by converting reactive aldehydes species to non-toxic alcohols inside living cells. These biorthogonal catalysts provide significant protection against cytotoxic aldehydes, such as 4-hydroxynon-2-enal and 4-oxonon-2-enal, and with greater potency than that of conventional aldehyde scavengers. We will discuss our ongoing efforts to develop targeted organoiridium catalysts and their potential to be used for combating difficult to treat diseases.

Host: Dr. Elizabeth Papish