Analysis of the molecular structure and vibrational spectra of the indole based analgesic drug indomethacin

The stability of the syn and anti structures of the non-steroidal anti-inflammatory drug indomethacin were investigated by the DFF-B3LYP and ab initio MP2 calculations with the 6-311G** basis set. The molecule was predicted at the DFT and MP2 levels of calculation to have the syn (C1N7C10C18 similar to 40 degrees) form being about 1.7 and 1.5 kcal/mol, respectively lower in energy than the anti (C1N7C10C18 similar to 140 degrees) structure. The calculated CNCC torsional angles for the chlorobenzene and indole rings syn-anti conformational interconversion was in a good qualitative agreement with the reported X-ray angles (C1N7C10C18 similar to 29 and 155 degrees) for the syn and anti conformers, respectively). Indomethacin was estimated from the calculated Gibbs free energies to have an equilibrium mixture of 95% syn and 5% anti structures at 298.15 K. The vibrational wavenumbers were computed at the B3LYP level of theory and complete vibrational assignments were provided on the basis of theoretical and normal coordinate calculations combined with experimental infrared and Raman data of the molecule. The analysis of the observed spectra supports the presence of indomethacin in only one conformation at room temperature. (C) 2013 Elsevier B.V. All rights reserved.