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A QSAR for the mutagenic potencies of twelve 2‐amino‐trimethylimidazopyridine isomers: Structural, quantum chemical, and hydropathic factors
Author(s) -
Knize M.G.,
Hatch F.T.,
Tanga M.J.,
Lau E.Y.,
Colvin M.E.
Publication year - 2006
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20177
Subject(s) - potency , chemistry , quantitative structure–activity relationship , mutagen , stereochemistry , ames test , homo/lumo , amine gas treating , computational chemistry , molecule , biochemistry , dna , organic chemistry , in vitro , salmonella , biology , genetics , bacteria
An isomeric series of heterocyclic amines related to one found in heated muscle meats was investigated for properties that predict their measured mutagenic potency. Eleven of the 12 possible 2‐amino‐trimethylimidazopyridine (TMIP) isomers were tested for mutagenic potency in the Ames/Salmonella test with bacterial strain TA98, and resulted in a 600‐fold range in potency. Structural, quantum chemical, and hydropathic data were calculated on the parent molecules and the corresponding nitrenium ions of all of the tested isomers to establish models for predicting the potency of the unknown isomer. The principal determinants of higher mutagenic potency in these amines are: (1) a small dipole moment, (2) the combination of b ‐face ring fusion and N3‐methyl group, (3) a lower calculated energy of the π electron system, (4) a smaller energy gap between the amine HOMO and LUMO orbitals (Pearson “softness”), and (5) a more stable nitrenium ion. Based on predicted potency from the average of six regression models, the isomer not yet synthesized and tested is expected to have a mutagenic potency of 0.77 revertants/μg in tester strain TA98, which is near the low end of the potency range of the isomers. Environ. Mol. Mutagen., 2006. © 2005 Wiley‐Liss, Inc.