A QSAR for the mutagenic potencies of twelve 2-amino- trimethylimidazopyridine isomers: Structural, quantum chemical, and hydropathic factors

Mark G. Knize, F. T. Hatch, M. J. Tanga, Edmond Y Lau, M. E. Colvin

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)132-146
Number of pages15
JournalEnvironmental and Molecular Mutagenesis
Volume47
Issue number2
DOIs
StatePublished - Mar 2006
Externally publishedYes

Fingerprint

Quantitative Structure-Activity Relationship
Isomers
Amines
Ions
Salmonella
Meat
Electrons
ion
Meats
Dipole moment
Muscles
meat
energy
Muscle
muscle
Energy gap
Fusion reactions
isomer
chemical
fold

Keywords

  • Cooking mutagen
  • Heterocyclic amine
  • QSAR
  • TMIP

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

A QSAR for the mutagenic potencies of twelve 2-amino- trimethylimidazopyridine isomers : Structural, quantum chemical, and hydropathic factors. / Knize, Mark G.; Hatch, F. T.; Tanga, M. J.; Lau, Edmond Y; Colvin, M. E.

In: Environmental and Molecular Mutagenesis, Vol. 47, No. 2, 03.2006, p. 132-146.

Research output: Contribution to journalArticle

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