Kolesnikova Inna N, Rykov Anatolii N, Shishkov Igor F, Tafeenko Victor A, Aslanov Leonid A
Department of Chemistry, M.V. Lomonosov Moscow State University, 119991 Moscow, Russia.
Phys Chem Chem Phys. 2017 Feb 8;19(6):4618-4626. doi: 10.1039/c6cp08401j.
This study presents the first determination of the molecular structure of the antihypertensive drug clonidine in the gas phase using gas electron diffraction (GED). The refinement was supported by quantum chemical calculations (QCs). The tautomeric and conformational distribution was investigated theoretically, providing an explanation for the presence of the single conformer in the gas phase. The molecular conformation of clonidine has been shown to have a nearly perpendicular arrangement of the phenyl and imidazolidine rings as described by the torsion angle C2-N6-C7-C8 = -72(6)°. The following structural parameters were obtained (bond lengths in Angstroms and bond angles in degrees with 3σ in parentheses): r(C-C) = 1.549(7), r(C-N) = 1.470(7), r(N-C) = 1.388(2), r(C[double bond, length as m-dash]N) = 1.286(7), r(C-N) = 1.388(2), r(C[partial double bond, bottom dashed]C) = 1.403(2), r(C-Cl) = 1.737(2); ∠(N-C-N) = 108.1(11), ∠(C-N-C) = 109.7(12), ∠(C-C-N) = 100.9(12), ∠(C-N[double bond, length as m-dash]C) = 122.5(12), ∠(C[partial double bond, bottom dashed]C[partial double bond, bottom dashed]C) = 114.9(2), and ∠(C[partial double bond, bottom dashed]C[partial double bond, bottom dashed]C) = 123.1(2). The standard enthalpy of formation of clonidine in the gas phase was calculated using G4 theory with both atomisation and isodesmic reaction approaches, yielding the corresponding value of . The molecular structure of clonidine in the solid phase was determined using X-ray diffraction (XRD). Clonidine crystallizes in the monoclinic space group P2/c as a twinned crystal. The imino-tautomer, as an equimolar mixture of the two conformers with geometries close to the enantiomeric pair, is present in the solid phase. The identical conformers are linked into centrosymmetric dimers by paired N-HN hydrogen bonds. The geometries of gaseous and solid clonidine differ especially in the immediate vicinity of the intermolecular hydrogen bonds formed in the crystal.
本研究首次使用气体电子衍射（GED）测定了气相中抗高血压药物可乐定的分子结构。该精修得到了量子化学计算（QC）的支持。从理论上研究了互变异构和构象分布，为气相中单一构象体的存在提供了解释。如扭转角C2-N6-C7-C8 = -72(6)°所示，可乐定的分子构象显示苯基和咪唑啉环几乎呈垂直排列。获得了以下结构参数（键长以埃为单位，键角以度为单位，括号内为3σ）：r(C-C)=1.549(7)，r(C-N)=1.470(7)，r(N-C)=1.388(2)，r(C=N)=1.286(7)，r(C-N)=1.388(2)，r(C-C)=1.403(2)，r(C-Cl)=1.737(2)；∠(N-C-N)=108.1(11)，∠(C-N-C)=109.7(12)，∠(C-C-N)=100.9(12)，∠(C-N=C)=122.5(12)，∠(C-C-C)=114.9(2)，以及∠(C-C-C)=123.1(2)。使用G4理论通过原子化和等键反应方法计算了气相中可乐定的标准生成焓，得出相应的值为 。使用X射线衍射（XRD）测定了固相可乐定的分子结构。可乐定以孪晶形式结晶于单斜空间群P2/c中。亚氨基互变异构体以两种构象体的等摩尔混合物形式存在于固相中，这两种构象体的几何形状接近对映体对。相同的构象体通过成对的N-HN氢键连接成中心对称二聚体。气态和固态可乐定的几何形状在晶体中形成的分子间氢键紧邻区域尤其不同。
