The bis-phenanthridinium system flexibility and position of covalently bound uracil finely tunes the interaction with polynucleotides

Abstract

A series of structurally similar bis-phenanthridinium derivatives, some with uracil at different positions, revealed different interactions with various polynucleotides. The uniform binding of mononucleotides to all studied compounds by “cyclobisintercaland” binding type indicated that compound–polynucleotide interaction selectivity was the consequence of polynucleotide secondary structure and not direct nucleobase recognition. Although affinity and fluorimetric response of all studied compounds toward ds-DNA/RNA was similar, the thermal denaturation and ICD signal-based sensing was highly sensitive to polynucleotide basepair composition and secondary structure. In particular, for the specific poly rAH⁺–poly rAH⁺ double helix MD parameters are newly developed and used for analysis of its complexes. The highly sensitive orientation of phenanthridinium as well as the role of the uracil substituent, both binding interactions finely tuned by the steric and binding properties of the DNA/RNA–ligand interaction site, offer novel structural information about binding and steric properties of particular DNA–RNA systems.