AbstractThe interaction of a series of 2‐phenylquinoline derivatives with RNA was investigated by means of viscometric, pKa, spectroscopic, binding,Tm, and kinetic methods. Compounds1,2, and3have a piperazyl substituent at thepara,meta, ororthoposition, respectively, while4has an unsubstituted phenyl ring. The pKa results suggest that1has three charges,2and3have more than two charges, and4has two charges at pH 6.2. Spectroscopic andTmresults indicate that1binds more strongly to RNA than2–4. Kinetic and modeling results indicate that1is a threading intercalator while2and4are classical intercalators. All experimental results indicate that3, which has a large twist between the phenyl and quinoline rings, binds weakly with RNA. © 1994 John Wiley&Sons,