Department of Chemistry, Materials, and Chemical Engineering "Giulio Natta", Politecnico di Milano, via L. Mancinelli 7, 20131, Milano, Italy.
Department of Chemistry, Visvesvaraya National Institute of Technology (VNIT), Nagpur, Maharashtra-, 440010, India.
Angew Chem Int Ed Engl. 2019 Sep 2;58(36):12456-12459. doi: 10.1002/anie.201907829. Epub 2019 Jul 30.
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.
尽管对挥发性麻醉剂的优先相互作用进行分子理解对于优化其药理活性非常重要，但目前的理解还相当有限。本文证实了氟烷作为氢键（HB）供体的能力，并首次提供了氟烷在固态和溶液中也作为卤素键（HaB）供体的实验证据。描述了一种氟烷/六甲基磷酰胺共晶，其单晶 X 射线结构显示溴或氯与磷酰基氧之间存在短 HaB。向氟烷溶液中加入二氮杂双环辛烷和四正丁基碘化铵后，会出现新的紫外/可见吸收带，表明氮原子和阴离子可能介导涉及氟烷的 HaB 驱动的结合过程。氟烷作为 HaB 和 HB 供体的双齿/三齿构筑体的能力为该试剂表现出的等变比提供了原子合理性。
