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Molecular Bases for Anesthetic Agents: Halothane as a Halogen‐ and Hydrogen‐Bond Donor
Author(s) -
Nayak Susanta K.,
Terraneo Giancarlo,
Piacevoli Quirino,
Bertolotti Federica,
Scilabra Patrick,
Brown John T.,
Rosokha Sergiy V.,
Resnati Giuseppe
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201907829
Subject(s) - halothane , chemistry , halogen , halogen bond , hydrogen bond , anesthetic , iodide , chlorine , inorganic chemistry , photochemistry , medicinal chemistry , molecule , alkyl , organic chemistry , anesthesia , medicine
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.