Calculations of the electronic structure of substituted indoles and prediction of their oxidation potentials

Density functional theory (DFT, DMo) and semi-empirical (PM3) calculations have been used to determine theoretical values for the standard redox poten tials for the oxidation of substituted indoles. The calculations have been corrected for solvation (COSMO) and for thermal effects (zero point energy and temperature variations in enthalpy and entropy) using frequency calcula tions. Good agreement between these theoretical values and those observed e xperimentally are found for the DFT calculations. The less rigorous semi-em pirical calculations produce a reasonable estimate of the redox potentials but show a greater discrepancy between experiment and theory. Quantum chemi cal DFT calculations on indole radical cations indicate that electron withd rawing 5-substituents show a similar spin density distribution in the aroma tic system, whereas electron donating substituents show a different distrib ution. This could explain the observed differences in the oxidation and sub sequent coupling reactions of indole radical cations with electron donating and those with electron withdrawing 5-substituents. Significant difference s are observed in the spin density distribution between these and previous semi-empirical calculations. This further emphasises the sensitivity of the se calculations to the level of accuracy of the computational method.