ИСТИНА

Molecular geometry and amino-imino tautomeric equilibrium within the cyclic guanidine fragment of moxonidine are of particular interest due its pharmacological activity [1], According to Density Functional Theory calculations at B3LYP/6-31G(d,p) level of theory, all amino forms are about 6 kcal/mol higher in energy than the imino. The imino-tautomer of moxonidine was found to consist of two conformers (conformer I and conformer II) and their enantiomeric forms. The geometries of both conformers were optimized at the B3LYP/6- 31G(d,p) and MP2/cc-pVTZ levels of theory. Conformer I is stabilized with an intramolecular N-H.. .0 hydrogen bond; the imidazolidine and pyrimidine rings adopt a non- planar orientation with a dihedral angle of 53° between the two rings. Conformer II is stabilized with intramolecular N-H.. .Cl contact with a dihedral angle of 67° between the two rings. MP2/cc-pVTZ computations indicate conformer II to be 0.2 kcal/mol higher in energy than conformer I. Neither of these intramolecular hydrogen bonded conformations is observed in the crystal. Instead, conformation with imidazolidine N-H oriented perpendicularly to pyrimidine ring with a dihedral angle of 88.9°[2] and devoid of intramolecular hydrogen bonds with ortho substituents is seen. Comparison of C-Cl bond lengths (in A) of moxonidine and clonidine determened from DFT calculations (this work) and X-ray diffraction study [2], Substance B3LYP/631 G(d,p) MP2/ccpVTZ Crystal moxonidine 1.764 1.740 1.721(2) clonidine 1.765 1.737 [1] Fenton, C.; Keating, G. M.; Lyseng-Williamson, K. A.; Moxonidine: a review of its use in essential hypertension, Drugs, 2006, 66, 477-496. [2] Nanubolu, J. B.; Sridhar, B., Ravikumar, K.; Understanding the amino imino tautomeric preference in (imidazole)imidazolidine-N-aryl(alcyl) systems: a case study of moxonidine drug and insights from the Cambridge structural database (CSD), CrystEngComm, 2014, 16, 10602-10617.