Solution conformation of the antitumor drug streptonigrin

The solution conformation of the antitumor drug streptonigrin in THF-d8 has been determined by dynamic 1H NMR spectroscopy (400 MHz). The major solution conformation agrees with the structure observed in the solid state [Chiu, Y.-Y.; Lipscomb, W. N. J. Am. Chem. Soc. 1975, 97, 2525-30]. Rings A, B, and C are coplanar, with ring C held in place by a hydrogen bond from the amino group on ring C and the pyridyl nitrogen in ring B. This conformation is stable in the range pH 3.9-8.9. At lower pH, the hydrogen bond is disrupted due to protonation of the pyridyl nitrogen in ring B. The major species present at pH 3.9-8.9 and 180 K is the zwitterion 1b (80%). Below 190 K, slow proton transfer between the free acid 1a and the zwitterion 1b is observed on the NMR time scale. Addition of a catalytic amount of base to the solution increases the rate of exchange 1a<-->1b, and only one set of resonances is observed. In CD2Cl2 this proton transfer is not observed. Implications for the structure(s) of metal complexes formed by streptonigrin are discussed.