Synthesis and DNA-binding properties of water-soluble cationic pyropheophorbides derived from chlorophyll a/b

Abstract

A series of mono-, di-, tetra- and hexacationic esters of pyropheophorbide a/b have been designed and synthesized to explore the intercalation of their phorbine ring between the base pairs of double-helical DNA and the influence of their peripheral substituents on the DNA interactions. Mono-(1), di-(2, 3) and tetra-(4, 5) cationic pyropheophorbides are soluble as an oligomeric aggregate in HEPES buffer, but hexa-(6) cationic pyropheophorbide is soluble as a monomer at lower concentrations. The interaction of these cationic pyropheophorbide derivatives with DNA has been investigated by DNA unwinding assay, fluorescence energy transfer, and measurements of the melting temperature of the double-helical DNA and visible absorption spectra. Dicationic 2 and 3 bind outside the double-helical DNA without and/or with self-aggregation and with self-aggregation, respectively, because they cannot intercalate between the base-pairs due to their aggregation. On the other hand, tetracationic 4 and 5 and hexacationic 6 intercalate between the base pairs of the double-helical DNA. The binding mode of the cationic pyropheophorbides a/b is strongly dependent on the number and position of the cationic peripheral substituents of the pyropheophorbides.