DNA polyintercalating drugs. Proton magnetic resonance studies of a new acridine dimer. Conformations and interactions with mono- and dinucleotides.

The conformation in aqueous solution of one acridine dimer which is able to bisintercalate in DNA (1, 14-bis(5-methoxy-6-chloro-9-acridinyl)-1,5,10,14-tetraazatetradecane tetrahydrochloride) (AcDi) and its interactions with mono- and dinucleotides have been investigated by fast Fourier transform proton magnetic resonance spectroscopy. Variations in chemical shifts of the most distingusihable protons of the acridine dimer with temperature bring evidence of a folded in equilibrium unfolded fast conformational equilibrium in the temperature range of 4-85 degrees C. Equilibrium parameters were estimated. The folded conformation has been deduced from iso-shielding curves of the acridine ring. In the complex between AcDi and 3'- or 5"AMP, and adenine ring is intercalated between the two acridine rings to give a sandwich-like complex. Studies of the interaction with adenylyl(3' leads to 5') adenosine (ApA) show two different complexes in equilibrium with the 3' or 5' moiety of ApA intercalated in the acridine dimer. These conclusions are derived from comparative studies with 2-methoxy-6-chloro-9-(3-dimethylaminopropylamino)acridine dihydrochloride which is the corresponding acridine monomer-(AcMo). In that case the self-association constant was determined. A model of the AcMo-5'-AMP complex was deduced from the analysis of the chemical shifts of the adenine protons. In this model, the N10+-D bond of the acridine points toward the negatively charged phosphate of the nucleotide.