Mechanism of binding of the radiosensitizers metronidazole and misonidazole (RO-07-0582) to bovine and human serum albumin: a proton NMR study

High-resolution proton NMR spectra of the radiosensitizer metronidazole and its derivative misonidazole (RO-07-0582) were measured in D2O at resonance frequency 60 MHz and interpreted in the aliphatic and aromatic regions. The linewidths of the NMR peaks attributed to individual fragments of nitroimidazole molecules were then analyzed in the presence of bovine and human serum albumin. With increasing concentration of serum albumin, a selectively larger broadening of the lines attributable to the protons of the aliphatic moieties than of those of the imidazole rings was observed for both compounds. This broadening for misonidazole strongly depends on the ionic strength of the solution. The results indicate a specific immobilization of the molecules of both radiosensitizers during their interaction with serum albumin and the involvement of the aliphatic chains of misonidazole and metronidazole as the primary binding sites