NMR Studies of metal complexes and DNA binding of the quinone-containing antibiotic streptonigrin

Optical and H NMR techniques have been applied to the study of a few metal complexes (Co, Fe, and Yb) of the antitumor antibiotic streptonigrin (SN) produced by Streptomyces flocculus to elucidate the structure of the complexes. The hyperfine-shifted H NMR signals of these paramagnetic complexes were fully assigned by means of relaxation and two-dimensional NMR techniques. These studies revealed that SN binds transition metal and lanthanide ions and forms stable metal–drug complexes, with the metal located at the quinolinequinone– picolinate site. This configuration requires a ≈1808 twist of the C2]C29 bond in the crystal structure of the drug. The hyperfine-shifted H NMR signals of the Co–SN complex are significantly changed upon addition of calf thymus DNA or poly[dA-dT], indicating direct binding of Co–SN complex with DNA.