Building blocks of eumelanin: Relative stability and excitation energies of tautomers of 5,6-dihydroxyindole and 5,6-indolequinone

Computation methods were used to examine the tautomerization equilibria for 5,6-dihydroxyindole (DHI, 2) and 5,6-indolequinone (IQ, 3). Relative energies were calculated at the B3LYP and PBE0 level of theory; solvent effects were modeled by using the CPCM method. Nine tautomers of 2 were examined. Our data showed that the generally accepted molecular structure of 2 corresponds to the most stable tautomer in both gas phase and aqueous solution. In aqueous solution, the quinone methide tautomer was the second most stable structure, being destabilized by 6 kcal mol(-1). In contrast, gas-phase DFT calculations on four tautomers of 3 suggest this compound exists as a mixture of two tautomers, the quinone and the quinone methide. The relative concentration of the quinone methide is predicted to be sufficient to be detected experimentally. The energy difference between these two tautomers increases in solution so concentration of quinone methide should be negligible in polar solvents. Vertical excitation energies for tautomers of 2 and 3 in solutions were obtained by combining TD-DFT techniques with the SCRF-CPCM calculations. Simulated absorption spectra in water were in semiquantitative agreement with available experimental data. Relatively strong absorption in near-IR range was predicted for 3. This spectral feature might be used to clarify the complex mechanisms of dihydroxyindole oxidation.