NMR-STUDIES OF CONFIGURATION AND TAUTOMERIC EQUILIBRIA IN NITROACRIDINE ANTITUMOR AGENTS

The solution configurations of the 1-nitroacridine nitracrine (a clinically used anticancer agent and experimental hypoxia-selective cytotoxin) and its nitro isomers were determined, as both free bases in CDC13 and as monocations (chromophore free base) and dications in D2O, by high-resolution proton magnetic resonance spectroscopy. The free bases of the 1-, 2-, and 3-nitro isomers exist in the aminoacridine configuration in CDC13 while the 4-nitro isomer appears to exchange slowly between the aminoacridine and iminoacridan configurations. As cations at pH 2 in D2O, all four isomers exist in the aminoacridine configuration. When the pH is increased to 7–8 to form the free bases of the nitroacridine chromophores, the 2- and 3-nitro isomers retain the aminoacridine configuration, but the 1- 4-nitro isomers convert to the iminoacridan configuration. These results are relevant to the ongoing discussion of aminoacridine-iminoacridan tautomerism of these acridine derivatives in solution. © 1990, American Chemical Society. All rights reserved.