title: [The role of stacking interactions in the mechanisms of clonidine binding].
abstract: The stacking interactions of the clonidine aromatic ring with the aromatic rings of Phe or Tyr of alpha2-adrenoreceptor and Tyr aromatic ring of the pore of the tetradotoxin-resistant channel have been investigated. Ab initio quantum chemical calculations for a model system of two parallel aromatic rings were performed by GAMESS software with 6-31G** basis set in the framework of the Moller-Plesset second-order perturbation theory with full geometry optimization without any symmetry. It was shown that the parallel shifted conformation of two aromatic rings is energetically most favorable. The 2,6-chlorination of one of the benzene rings leads to the amplification of the stacking interaction, an increase in the relative shift of the rings and possible growth of both the hypotensive and analgetic functions of clonidine due to the increase in the binding energy. The 4-fluoridization of the clonidine benzene ring can amplify its analgetic function but practically excludes its hypotensive action.
authors.forename: B F
authors.initials: BF
authors.lastname: Shchegolev
authors.forename: E V
authors.initials: EV
authors.lastname: Shliakhto
authors.forename: R S
authors.initials: RS
authors.lastname: Khrustaleva
authors.forename: I E
authors.initials: IE
authors.lastname: Katina
authors.forename: V A
authors.initials: VA
authors.lastname: Tsyrlin
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry; D003000:Clonidine / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D011789:Quantum Theory
chemical_list: D000316:Adrenergic alpha-Agonists; D000596:Amino Acids; D003000:Clonidine