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.