2 PYRIDONE AS A MODEL NUCLEOPHILE FEASIBILITY STUDY

2 -PYRIDONE AS A MODEL NUCLEOPHILE

FEASIBILITY STUDY 2 -Pyridone as a model system for predicting site-specificity of mutagen attack on DNA by Ms. Xiang Wang Master of Science Thesis University of Minnesota Robert M. Carlson Adviser March 1994

METHODS §- HPLC/MS and GC/MS identification of adducts §- Sodium salt of 2 -pyridone mixed 1: 1 molar ratios §- Acetonitrile media at room temperature §- Measure adduct formation over time (<24 hours)

Electrophile N-Alkylated (10 - O-Alkylated (10 O/N Ratio 4) -4 ) I odomethane 32. 8 ND O Iodothane 24. 4 3. 16 0. 13 2 -idopropane 1. 33 3. 75 2. 83 Dimethyl sulfate 24. 6 4. 32 0. 17 Diethyl sulfate 22. 7 9. 79 0. 43 Nitroso methylurea 2. 16 17. 9 8. 3 Nitroso methylurethane 21, 0 19. 4 0. 92 Trimethylphosphite ND ND --- Dimethylphosphite ND ND --- Trimethylphosphate ND ND --- Styrene oxide ND --- ND

Electrophile N-Alkylated (104) O/N Ratio Allyl iodide 33. 19 0. 097 Allyl bromide 26. 3 2. 46 0. 093 Allyl chloride 17. 3 ND 0 1, 3 -dichloro-1 propene 22. 8 1. 32 0. 058 3 -chloro-1 -butene 0. 41 ND 0 3 -chloro cyclohexene 0. 683 1. 03 1. 50 benzylchloride 22. 3 1. 46 0. 066 Crotyl chloride 1. 8 1. 51 0. 13

Electrophile N-Alkylation(10 -4) O/N Ratio S. Typhimurium mutangenicity Methyl nitrosourea 2. 16 8. 32 841 Ethyl nitrosourea 3. 51 6. 11 202 Ethylmethylane sulfate 15. 6 0. 18 1. 70 Diethylsufate 22. 7 0. 43 24. 4 Dimethyl sulfate 24. 6 0. 17 5. 8 Methyl methane sulfonate 33. 7 0. 036 0. 8