The structure of betaxolol from single crystal X-ray diffraction and natural bond orbital analysis

The structure of betaxolol obtained from ethanol:water solution was studied by X-ray diffraction. The geometrical parameters needed to define the structure are tabulated. The X-ray data show the existence of two conformers in the unit cell differing only in the conformation of the cyclopropylmethoxy fragment. Differences in the bond lengths angles and dihedral between both conformations are observed. The cyclopropyl groups lie in approximately perpendicular planes.The two molecular geometries identified by single crystal X-ray diffraction were optimized at the B3LYP/6-31G(d,p) level of theory. Both isolated molecules are retained as distinct conformers upon geometry optimization, despite some dihedral relaxation.The electronic structure of the most important molecular fragments was described in terms of Natural Bond Orbitals. The energetic and spatial features of the occupied and vacant orbitals were studied.The different structures observed in the solid state were explained by the specific interactions involving the oxygen lone pairs in cyclopropylmethoxy. It was observed some orbital and geometry distortion in cyclopropyl caused by the crystal packing.