Hypericin derivatives: Substituent effects on radical-anion formation

The electron-transfer properties of the hypericin derivatives, dibromo-, he xaacetyl-, hexamethyl- and desmethylhypericin, were studied. Cyclovoltammet ric measurements revealed that dibromo- and desmethylhypericin have almost the same redox potentials as the parent hypericin. Substitution of the hydr oxyl groups by acetoxy leads to less negative E-1/2 values, whereas methoxy substitution induces more negative values. Electron paramagnetic resonance (EPR)/electron nuclear double resonance/general TRIPLE spectroscopy and qu antum mechanical calculations were used to establish the structure of the o ne-electron reduced stages of hypericin derivatives. Proton loss in the bay region, already demonstrated for hypericin, was also found for dibromo- an d desmethylhypericin. The spin and charge of the radical ions are predomina tely confined to the central biphenoquinone moiety of the hypericin skeleto n. Generation of the radical ions by in situ electrolysis indicates that th e redox potentials of hypericin, dibromo- and desmethylhypericin, containin g hydroxyls at the 1, 3, 4, 6, 8 and 13 positions, largely depend on the so lvent. With phosphate-buffered saline (pH 7.4)/dimethylsulfoxide (DMSO) as the solvent the EPR spectra of the corresponding radical ions appear at mar kedly lower potentials than in pure DMSO and NN'-dimethylformamide. However , this effect is not observable for hexaacetyl- and hexamethylhypericin-lac king hydroxyl groups. In all cases the EPR data and calculations revealed t he presence of 7,14 tautomers.