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

Abstract

Optical and ¹H NMR techniques have been applied to the study of a few metal complexes (Co²⁺, Fe²⁺, and Yb³⁺) of the antitumor antibiotic streptonigrin (SN) produced by Streptomyces flocculus to elucidate the structure of the complexes. The hyperfine-shifted ¹H 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 ≈180° twist of the C2–C2′ bond in the crystal structure of the drug. The hyperfine-shifted ¹H NMR signals of the Co²⁺–SN complex are significantly changed upon addition of calf thymus DNA or poly[dA-dT], indicating direct binding of Co²⁺–SN complex with DNA.