Biopolymers and cell. 1998; 14 (2): 117 - 126

H-NMR investigation of coraplexation of acridine dye proflavine with deoxytetraribonucleoside triphosphate S'-d(TpGpCpA) in aqueous solution

R. A. Eaton, D. A. Veselkov, L. N. Djimant, S. F. Baranovsky, S. G. Osetrov, D. B. Davies, A. N. Veselkov

The interaction of acridine dye proflavine with self-complementary deoxytetraribonucleoside triphosphate S'-d(TpGpCpA) in aqueous salt solution has been studied by one- and two- dimentional 500 MHz H-NMR spectroscopy. Concentration and temperature de¬pendences of proton chemical shifts of the interacting molecules have been measured. Different schemes of complexation of pro¬flavine with the tetranucleotide have been analysed and the equi¬librium constants, enthalpies A//, entropies AS of different reactions leading to the formation of 1:1, 1:2, 2:1, 2:2 complexes have been determined. The specific features of the dynamic equilibrium of different complexes as a function of the drug-tetranucleotide ratio have been examined. It is concluded that proflavine intercalates preferentially to pyrimidine-purine TG- and CA-sites of the tetra¬nucleotide sequence. Comparative analysis of the distinctive features of the intercalative binding of proflavine and that of phenan-tridinium dye ethidium bromide studied earlier has shown that intensity of selective interaction of aromatic ligands with pyrimi¬dine-purine sequence depends on the base content and type of the bases flanking the binding sites. The most favourable structures 1:2 and 2:2 proflavine-tetranucleotide complexes have been constructed using calculated values of induced chemical shift of dye protons and 2D-NOE spectra.