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 language | English (US) |
|---|---|
| Pages (from-to) | 132-146 |
| Number of pages | 15 |
| Journal | Environmental and Molecular Mutagenesis |
| Volume | 47 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 2006 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - A QSAR for the mutagenic potencies of twelve 2-amino- trimethylimidazopyridine isomers
T2 - Structural, quantum chemical, and hydropathic factors
AU - Knize, Mark G.
AU - Hatch, F. T.
AU - Tanga, M. J.
AU - Lau, Edmond Y
AU - Colvin, M. E.
PY - 2006/3
Y1 - 2006/3
N2 - 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.
AB - 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.
KW - Cooking mutagen
KW - Heterocyclic amine
KW - QSAR
KW - TMIP
UR - http://www.scopus.com/inward/record.url?scp=33644607911&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33644607911&partnerID=8YFLogxK
U2 - 10.1002/em.20177
DO - 10.1002/em.20177
M3 - Article
C2 - 16258923
AN - SCOPUS:33644607911
VL - 47
SP - 132
EP - 146
JO - Environmental and Molecular Mutagenesis
JF - Environmental and Molecular Mutagenesis
SN - 0893-6692
IS - 2
ER -