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, an both free bases in CDCl3 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 CDCl3, 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- and 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.
Boyd
M
M
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
Denny
W A
WA
D000609:Aminoacridines; D000970:Antineoplastic Agents; D055598:Chemical Phenomena; D002621:Chemistry; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D009564:Nitracrine / Q000031:analogs & derivatives; D009574:Nitro Compounds; D013329:Structure-Activity Relationship
D000609:Aminoacridines; D000970:Antineoplastic Agents; D009574:Nitro Compounds; D009564:Nitracrine