Synthesis of analogues of a flexible thiopyrylium photosensitizer for purging blood-borne pathogens and binding mode and affinity studies of their complexes with DNA.

A series of thio- and selenopyrylium analogues of 2,4-di(4-dimethylaminophen-yl)-6-methylthiopyrylium iodide were prepared in five steps from 4-dimethylaminophenyl-propargyl aldehyde and the corresponding lithium acetylide. When bound to DNA, all of the dyes absorb at wavelengths >600nm, which avoids the hemoglobin band I maximum at 575nm. The binding of the series of dyes to double-stranded DNA was examined spectrophotometrically and by isothermal titration calorimetry to determine binding constants, by a topoisomerase I DNA unwinding assay, by competition dialysis with poly(dGdC) and poly(dAdT), and by ethidium bromide displacement studies to examine propensities for intercalation, and by circular dichroism studies. The dyes were found to show mixed binding modes.