Alicia O. Hernandez-Castillo Anesthetic Binding

Towards a Molecular Scale Understanding of Anesthetic Binding

Anesthetics are used every day in thousands of hospitals to induce reversible loss of consciousness. Yet the mechanism through which they work is still a pharmacological puzzle. Understanding the mechanism of action of general anesthetics requires the identification of their binding sites and modes of binding. Taking a physical chemistry approach to this mystery, our group – using rotational spectroscopy – can provide fundamental data on the intermolecular interactions between anesthetics and key molecular components of the target binding sites.

Currently we are focusing on Xe-Indole clusters. Xenon produces a state of general anesthesia in several species, including humans. However, the precise underlying mechanism by which it produces this anesthetic effect remains unclear. The Xe atoms are thought to participate in competitive inhibition of the NMDA receptor by binding at the glycine binding site in the receptor, which contains aromatic residues such as tryptophan (Trp). If Xe binds to this site, its interaction is likely to be dominated by the indole ring of Trp. Our first step it to determine how Xe interacts with indole.  To do this, we will need to form the complex in a supersonic expansion and then study their broadband microwave spectrum.