Synthesis and Properties of Hypericins Substituted with Acidic and Basic Residues: Hypericin Tetrasulfonic Acid – A Water Soluble Hypericin Derivative

Abstract

Sulfonation of hypericin leads to its di-, tri-, and tetrasulfonic acid derivatives. The latter is soluble in water up to millimolar solutions. Homoaggregate formation (J-aggregates) was observed only above 5ċ10−4 mol/l. In water solutions, the tetrasulfonic acid hypericin derivative was found to be present as its bay-phenolate with most of the sulphonic acids dissociated. Thus, the first water soluble hypericin derivative, which in contrast to hypericin is not prone to homoassociation, is presented. Hypericin tetrtasulfonic acid forms heteroassociates with serum albumin, DNA, and γ-cyclodextrin. Hypericin derivatives with primary and tertiary amino group appendages at the hypericin methyl groups were synthesized. However, upon salt formation or quaternization these derivatives became virtually insoluble in all common solvents including water.