| Summary: | Interactions of an array of nucleic acid structures with a small series of benzothiazole ligands (bis-benzothiazolyl-pyridines—group 1, 2-thienyl/2-benzothienyl-substituted 6-(2-imidazolinyl)benzothiazoles—group 2, and three 2-aryl/heteroaryl-substituted 6-(2-imidazolinyl)benzothiazoles—group 3) were screened by competition dialysis. Due to the involvement of DNA:RNA hybrids and triplex helices in many essential functions in cells, this study’s main aim is to detect benzothiazole-based moieties with selective binding or spectroscopic response to these nucleic structures compared to regular (non-hybrid) DNA and RNA duplexes and single-stranded forms. Complexes of nucleic acids and benzothiazoles, selected by this method, were characterized by UV/Vis, fluorescence and circular dichroism (CD) spectroscopy, isothermal titration calorimetry, and molecular modeling. Two compounds (<b>1</b> and <b>6</b>) from groups 1 and 2 demonstrated the highest affinities against 13 nucleic acid structures, while another compound (<b>5</b>) from group 2, despite lower affinities, yielded higher selectivity among studied compounds. Compound <b>1</b> significantly inhibited RNase H. Compound <b>6</b> could differentiate between B- (binding of <b>6</b> dimers inside minor groove) and A-type (intercalation) helices by an induced CD signal, while both <b>5</b> and <b>6</b> selectively stabilized ATT triplex in regard to AT duplex. Compound <b>3</b> induced strong condensation-like changes in CD spectra of AT-rich DNA sequences.
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