Time‐dependent density functional theory calculations on the chiroptical properties of rubroflavin: Determination of its absolute configuration by comparison of measured and calculated CD spectra

The absolute configuration of rubroflavin has been determined by comparison of its measured and calculated CD spectra. For this purpose the structures of 30 plausible isomers of the title compound have been optimized with density functional theory (DFT/BP86) using a triple‐zeta valence basis set. The absolute (S) configuration at the ? S(?O)CH₃ group has been assumed in these calculations. One quinoid isomer, which is separated from all other structures by an energy gap of about 4 kcal/mol, was found to be the most stable species and to dominate the CD spectrum. The structure of this isomer has been reoptimized under the influence of a solvent using an electrostatic model (COSMO). Based on the geometries of the most stable isomer obtained in the presence and absence of the solvent the excitation energies and oscillator as well as rotational strengths have then been calculated using time‐dependent DFT (TDDFT/TZVP/BP86). Comparison of the measured CD spectrum with that calculated for the energetically lowest isomer shows that especially the long wavelength parts of the spectra agree fairly well as far as the wavelengths and the signs of the Cotton effects are concerned while the correspondence between calculated and measured intensities is less satisfying. The agreement between the measured and calculated spectrum is better if the geometry optimized under the influence of the solvent is used. A detailed analysis of the spectra led us to the conclusion that the absolute configuration of rubroflavin is (S). These results support earlier assignments based on semiempirical and ab initio studies on a thermal decomposition product of rubroflavin. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 93: 265–270, 2003