Molecular Bases for Anesthetic Agents: Halothane as a Halogen‐ and Hydrogen‐Bond Donor

Although instrumental for optimizing their pharmacological activity, a molecular understanding of the preferential interactions given by volatile anesthetics is quite poor. This paper confirms the ability of halothane to work as a hydrogen‐bond (HB) donor and gives the first experimental proof that halothane also works as a halogen‐bond (HaB) donor in the solid state and in solution. A halothane/hexamethylphosphortriamide co‐crystal is described and its single‐crystal X‐ray structure shows short HaBs between bromine, or chlorine, and the phosphoryl oxygen. New UV/Vis absorption bands appear upon addition of diazabicyclooctane and tetra(n‐butyl)ammonium iodide to halothane solutions, indicating that nitrogen atoms and anions may mediate the HaB‐driven binding processes involving halothane as well. The ability of halothane to work as a bidentate/tridentate tecton by acting as a HaB and HB donor gives an atomic rationale for the eudismic ratio shown by this agent. Doppelter Brückenschlag: Experimente bestätigen die Fähigkeit des flüchtigen Anästhetikums Halothan, Halogen‐ und Wasserstoffbrücken mit Atomen, die nichtbindende Elektronenpaare enthalten, sowohl im Festkörper als auch in Lösung zu bilden. Hierdurch ergeben sich neue Einblicke in das Verständnis von Halothan‐Membran‐Wechselwirkungen und anderen Eigenschaften des Agens wie z. B. seines eudismischen Verhältnisses.