Syntheses and DNA photocleavage by mono- and bis-phenothiazinium–piperazinexylene intercalators

Chromophore systems consisting of one (compound 5) or two (compound 6) phenothiazine rings covalently attached to a bis-piperazinexylene chain were synthesized and evaluated as DNA photocleaving agents. In the presence of DNA, the compounds were shown to monointercalate in their deaggregated forms and to strongly absorb red wavelengths of light. Reactions containing micromolar concentrations of compound produced robust photocleavage of plasmid DNA under near-physiological conditions of temperature and pH (22 °C and pH 7.0). Phenothiazines 5 and 6 increased the Tm of calf thymus DNA by 17 and 19 °C, indicating that significant levels of duplex stabilization were produced.