Antitumor antibiotic, Chromomycin A₃ (CHR), inhibits DNA replication and transcription via reversible interaction with double stranded DNA with GC-base specificity. The interaction, at and above physiological pH, requires the presence of bivalent metal ions, such as Mg²⁺. Anionic antibiotic does not bind DNA in the absence of Mg²⁺. In this paper we have examined the structural potential of neutral CHR at pH 5.2 to bind DNA in the absence of Mg ²⁺.

We have demonstrated the ability of the neutral antibiotic to bind DNA by means of different spectroscopic techniques and evaluated the necessary thermodynamic parameters for elucidation of the molecular basis of recognition. The results are compared with the scenario when Mg²⁺ is present in the system, because the ultimate aim of these studies is to elucidate the role of Mg²⁺ in CHR-DNA recognition.

Neutral CHR binds to Mg²⁺ with lesser affinity than its anionic form. Spectroscopic features of the drug and its Mg²⁺ complex indicate self association of the antibiotic in the absence and presence of Mg²⁺. GC-base specificity of the drug and its Mg²⁺ complex are retained at pH 5.2, though the modes of recognition of DNA by the two ligands are different. Minor groove width of DNA plays a role in the accommodation of the ligand(s) during the GC base specific recognition while positive charge of Mg²⁺ in CHR:Mg²⁺ complex further facilitates the association. Relatively lower affinity of the neutral drug and its Mg²⁺ complex for DNA can be ascribed to the self association of these ligands in the absence of DNA.