• Jin Xi, Renyu Liu, Matthew J Rossi, Jay Yang, Patrick J Loll, William P Dailey, and Roderic G Eckenhoff.
• Department of Anesthesiology & Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
• ACS Chem. Biol. 2006 Jul 21; 1 (6): 377-84.

AbstractThe difficulty in obtaining binding target and site information for low-affinity drugs, like the inhaled anesthetics, has limited identification of their molecular effectors. Because such information can be provided by photoactive analogues, we designed, synthesized, and characterized a novel diazirnyl haloether that closely mimics isoflurane, the most widely used clinical general anesthetic. This compound, H-diaziflurane, is a nontoxic, potent anesthetic that potentiates GABA-gated ion channels in primary cultures of hippocampal neurons. Calorimetric and structural characterizations show that H-diaziflurane binds a model anesthetic host protein with similar energetics as isoflurane and forms photoadducts with residues lining the isoflurane binding site. H-diaziflurane will be immediately useful for identifying targets and sites important for the molecular pharmacology of the inhaled haloether anesthetics.

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