On the Tautomers of Hypericin

Abstract

Hypericin has 16 theoretically conceivable tautomers (10 with and 6 without Kekule structural formulas). AM1 calculations show that two factors determine the relative stability of the tautomers. The dominant factor is the mode of conjugation of the π-electrons. A less pronounced, yet significant, factor is the steric repulsion of the carbonyl and/or hydroxy groups in positions 3 and 4. Among tautomers with equal π-electron conjugation, the least stable are those having carbonyl groups in positions 3 and/or 4. The tautomer Q(7, 14), with carbonyl groups in positions 7 and 14, is the far most stable one; the next two tautomers –Q(1, 7) and Q(7, 13) – have by some 40 kJ/mol higher energies, followed by Q(3, 7), Q(8, 13), and Q(1, 6) with energies 60, 70 and 70 kJ/mol above the energy of Q(7, 14), etc. The energy values of the hypothetical tautomers without Kekule structures lie 150–200 kJ/mol above Q(7, 14); therefore, these are of no practical relevance.