STUDY OF THE FORCES 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 pr evious 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 CHI in the Salmonella essay. The present investigation utilized molecular me chanics methods of energy minimization and spectrophotometric titratio n to examine structural features of chlorophylls, chlorins, and porphy rins that might be important for complex formation with heterocyclic a mines. The exocyclic amine group of the mutagen aligned consistently w ith acid groups in CHL, suggesting that H-bond or electrostatic intera ctions facilitate complex formation. Replacement of the exocyclic amin e with a nitro group abrogated this specific orientation and raised th e minimized energies of the complexes. No relationship was found betwe en complex strength and the specific positions of amine or methyl grou ps on the mutagen. However, the presence of methyl groups increased th e minimized energies and lowered the binding constants of the complexe s, perhaps due to partial disruption of pi-pi interaction by steric ef fects. All of the compounds examined, including chlorophyll a, require d the presence of pi-pi. interactions to form stable complexes with th e heterocyclic amines. In general, the present results were in agreeme nt with the inhibitory potency of each compound in the Salmonella assa y, and they provide further support for the hypothesis that chlorophyl ls in the diet might act as interceptor molecules of food-borne carcin ogens and mutagens. (C) 1996 Wiley-Liss, Inc.