Study of the forces of stabilizing complexes between chlorophylls and heterocyclic amine mutagens.
Chlorophyllin (CHL), a water-soluble derivative of chlorophyll, forms molecular complexes with heterocyclic amine mutagens in vitro. In a previous study [Dashwood and Guo (1993): Environ Mol Mutagen, 22:164-171], we observed an inverse correlation between the binding constants of several mutagen-CHL complexes and the antimutagenic potency of CHL in the Salmonella assay. The present investigation utilized molecular mechanics methods of energy minimization and spectrophotometric titration to examine structural features of chlorophylls, chlorins, and porphyrins that might be important for complex formation with heterocyclic amines. The exocyclic amine group of the mutagen aligned consistently with acid groups in CHL, suggesting that H-bond or electrostatic interactions facilitate complex formation. Replacement of the exocyclic amine with a nitro group abrogated this specific orientation and raised the minimized energies of the complexes. No relationship was found between complex strength and the specific positions of amine or methyl groups on the mutagen. However, the presence of methyl groups increased the minimized energies and lowered the binding constants of the complexes, perhaps due to partial disruption of pi-pi interaction by steric effects. All of the compounds examined, including chlorophyll a, required the presence of pi-pi interactions to form stable complexes with the heterocyclic amines. In general, the present results were in agreement with the inhibitory potency of each compound in the Salmonella assay, and they provide further support for the hypothesis that chlorophylls in the diet might act as interceptor molecules of food-borne carcinogens and mutagens.
Dashwood
R
R
Department of Environmental Biochemistry, University of Hawaii, Honolulu 96822, USA.
Yamane
S
S
Larsen
R
R
D000588:Amines / Q000737:chemistry*; D016587:Antimutagenic Agents / Q000737:chemistry* / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002734:Chlorophyll / Q000737:chemistry* / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry*; D012486:Salmonella typhimurium / Q000187:drug effects; D013053:Spectrophotometry; D013329:Structure-Activity Relationship
D000588:Amines; D016587:Antimutagenic Agents; D006571:Heterocyclic Compounds; D009153:Mutagens; D002734:Chlorophyll