Substituent control of DNA binding modes in a series of chalcogenoxanthylium photosensitizers as determined by isothermal titration calorimetry and topoisomerase I DNA unwinding assay

The binding of a series of rhodamine-related chalcogenoxanthylium dyes to DNA was measured using isothermal titration calorimetry and a topoisomerase I DNA unwinding assay. The DNA binding efficacy and preferred mode of binding of a series of rhodamine-related chalcogenoxanthylium dyes was investigated by isothermal titration calorimetry (ITC) using ctDNA, [poly(dCdG)] 2 and [poly(dAdT)] 2, and by a topoisomerase I DNA unwinding (Topo I) assay. The dyes of this study showed tight binding to ctDNA with binding constants, K b, on the order of 10 6–10 7 M −1. The ITC and Topo I assay studies suggested that the 9-substituent has a strong impact on binding modes ranging from an apparent preference for intercalation with a 9-2-thienyl substituent (similar binding to [poly(dCdG)] 2 and [poly(dAdT)] 2, re-supercoiling of DNA in the Topo I assay at