Conformational study of isolated pindolol by HF, DFT and MP2 calculations

In the present work a conformational analysis of pindolol, a beta-blocker, is performed using several computational methods, including HF, DFT (B3LYP) and MP2. The relative electronic energies as well as the relevant dihedral angles of the significant conformer geometries are reported. At the HF and DFT levels the most stable conformers of pindolol are characterized by an extended backbone structure, minimizing the steric repulsions between the indole ring and the side chain. The two backbone dihedrals, defining the position of the ring relatively to the side chain, are found to be particularly important. The lower energy structures obtained by HF and DFT also contribute significantly to the MP2 conformational population. This last method increases the stability of some conformers presenting a more folded backbone. Most conformers exhibit hydrogen bonding. This feature, although not being the dominant factor in energetic terms, appears to be of foremost importance to define the geometry of the molecule. Four intramolecular hydrogen bonds established between the polar groups were identified by the structural geometric parameters. These involved the hydroxyl and amine functional groups and were identified and characterized by the frequency shift in their stretching vibration modes. (c) 2006 Elsevier B.V. All rights reserved.