Structure-selective binding and bioactivity of chlorine-substituted cyanine dyes with DNA, RNA, and lipid membranes

A comprehensive physicochemical and biological evaluation of three cyanine dyes revealed clear structure-dependent differences in their interactions with nucleic acids, lipid membranes, and cells. Two monomethine derivatives interacted moderately and non-specifically with ds-DNA/RNA, producing weak thermal stabilisation and no induced CD signals, consistent with external binding. The monomethine benzoxazole-containing dye showed strong antibacterial activity against Staphylococcus aureus , comparable to ampicillin, and promising anticancer activity with selectivity over normal fibroblasts. In contrast to monomethine derivatives, the trimethine dye displayed highly selective nucleic acid recognition, including a dual fluorimetric response toward AU-RNA and distinct induced CD signatures for all examined polynucleotides. It's marked ICD differences between monomeric and aggregated species—especially the opposite helical arrangements detected for GC- and IC-DNA—demonstrate a remarkably high level of structural sensitivity for dyes of this class. The trimethine dye further discriminated Tel22 G-quadruplex topologies in K + and Na + solutions through ICD signature. Altogether, it emerges as a highly structure-responsive probe capable of differentiating nucleic acid conformations via both fluorescence and ICD readouts, highlighting the broader potential of chlorinated cyanine dyes for nucleic acid sensing and biomedical applications.