Interactions of tetracycline and its derivatives with DNA in vitro in presence of metal ions

The interactions of calf thymus DNA with tetracycline (TC), 7-chlorotetracycline (CTC) and 6-dimethyl-7-chlorotetracycline (DMTC) were assessed employing spectrofluorometric and circular dichroism (CD) techniques. The Scatchard analysis revealed relatively lesser binding affinity of TC (Ka= 1.2 x 10(7) lmol(-1)) vis-a-vis CTC (Ka= 3.4 x 10(7) lmol(-1)) and DMTC (Ka= 3.0 x 10(7) lmol(-1)) with DNA. The data suggested both the intercalative and electrostatic nature of binding between the tetracyclines and DNA. The presence of Cu(II) augmented the interaction of tetracyclines with DNA, and resulted in red shift by 12 nm in CD spectra of tetracycline. The molar ellipticity (theta) also changed significantly for CTC and DMTC. The data unequivocally demonstrated the DNA binding potential of tetracyclines both in the presence and absence of Cu(II) ions in dark. The enhanced binding of tetracyclines in presence of Cu(II), ensuing conformational changes in DNA secondary structure to a varying extent, reflects differential reactivity of ligand chromophores.