Liquid-crystalline Structure of Nucleic Acids: Effect of Antracycline Drugs and Copper Ions

Abstract

The formation of liquid-crystalline dispersions (L.C.D.) from double-stranded DNA and polynucleotide (NA) molecules complexed with a number of anthracycline derivatives was investigated. These drugs form two types of complexes (complex I and complex II) with NA, which differ in the mode of drug orientation in respect to the NA helical axis. When complex II forms, addition of copper ions causes bridging of neighboring NA molecules through polymeric copper-anthracycline links (Figure 1). This results in an extra-increase in the amplitude of the intense CD band, characteristic for complex II, in the drug absorption region. Comparison of data obtained for different analogs and derivatives of daunomycin, has shown that the presence of 4 coordinating oxygen atoms at positions 5,6 and 11,12 (or 1,12) of the anthracycline ring system represents the basic prerequisite for the formation of a long polymeric chelate bridge after addition of copper ions. A second requirement relates to the chemical and stereochemical properties of sugar residues at position 7. These are important for proper positioning of the neighboring anthracycline aglycones in the polymeric chelate bridges and for spatial fixation of Cu2+ ions. Base sequence of double-stranded polynucleotides plays, if any, a minor role in polymeric chelate bridge formation. The question concerning the sterical orientation of two neighbouring antracyclines in the linking bridges, formed between NA molecules fixed in the liquid-crystalline structure, remains open.