Benzothienoquinolines: New one-pot synthesis and fluorescence studies of their interaction with DNA and polynucleotides

Abstract

Abstract In this work, we were able to obtain the benzothieno[3,2- b ]quinoline 1 and benzothieno[2,3- c ]quinoline 2 using a new one-pot procedure from the reaction of the commercially available 3-bromobenzo[ b ]thiophene-2-carbaldehyde with 2-aminophenylpinacolborane under Suzuki coupling conditions using a stereochemically hindered ligand, 2-(cyclohexylphosphane)biphenyl and Ba(OH) 2 ·8H 2 O as the base. Fluorescence properties of the benzothieno[3,2- b ]quinoline 1 and the benzothieno[2,3- c ]quinoline 2 were studied in solvents of different polarity. Both compounds exhibit a solvent sensitive emission, compound 1 being less fluorescent ( Φ F 2 (0.04 ≤ Φ F ≤ 0.10). The interaction of these compounds with salmon sperm DNA and synthetic double-stranded heteropolynucleotides, poly(dA–dT)·(dA–dT) and poly(dG–dC)·(dG–dC), was studied using spectroscopic methods, allowing the determination of the intrinsic binding constants and binding site sizes. The interaction of both compounds is stronger with adenine–thymine (A–T) base pairs. Compound 1 is the most intercalative in salmon sperm DNA (47%) and polynucleotides (46–49% of intercalated molecules), while for compound 2 , 41% is intercalated in salmon sperm DNA and only 8% in poly(dG–dC)·(dG–dC). Docking studies indicate that compound 1 interacts more strongly with DNA than compound 2 , with a significant value of binding free energy in the case of intercalation. Minor groove binding is also very favourable and, probably, both mechanisms occur with a preponderance of intercalation in the case of compound 1 . Overall, these results indicate that both benzothienoquinolines interact with nucleic acids by both intercalation and groove binding.