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

Abstract

Density functional theory (DFT, DMol³) and semi-empirical (PM3) calculations have been used to determine theoretical values for the standard redox potentials 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 calculations. Good agreement between these theoretical values and those observed experimentally are found for the DFT calculations. The less rigorous semi-empirical calculations produce a reasonable estimate of the redox potentials but show a greater discrepancy between experiment and theory. Quantum chemical DFT calculations on indole radical cations indicate that electron withdrawing 5-substituents show a similar spin density distribution in the aromatic system, whereas electron donating substituents show a different distribution. This could explain the observed differences in the oxidation and subsequent coupling reactions of indole radical cations with electron donating and those with electron withdrawing 5-substituents. Significant differences are observed in the spin density distribution between these and previous semi-empirical calculations. This further emphasises the sensitivity of these calculations to the level of accuracy of the computational method.