Oxidative Repair of Pyrimidine Cyclobutane Dimers by Nitrate Radicals (NO3•): A Kinetic and Computational Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Synthesis of the Pyrimidine Cyclobutane Dimers
2.1.1. General
2.1.2. Synthesis of N-Methylated Pyrimidines
1,3-Dimethyluracil (DMU)
1,3-Dimethylthymine (DMT)
1,3.6-Trimethyluracil (DMU6-Me)
2.1.3. Dimerization of N-Methylated Pyrimidines
Synthesis of DMU<>DMU Isomers
- (a)
- t,a-DMU<>DMU: White crystals (0.35 g, 1.25 mmol, 3%, Rf = 0.26 (EtOAc)). 1H-NMR (400 MHz, CDCl3): δ 4.10 (dd, J = 9.4, 4.9 Hz, 2H), 3.53 (dd, J = 9.4, 4.9 Hz, 2H), 3.24 (s, 6H), 3.08 ppm (s, 6H). 13C {1H}-NMR (101 MHz, CDCl3): δ 167.1 (2C), 151.6 (2C), 53.7 (2C), 44.5 (2C), 33.8 (2C), 28.1 ppm (2C). HRMS (ESI) m/z calcd. for [C12H17N4O4]+: 281.1250 [M + H]+, found 281.1245.
- (b)
- t,s-DMU<>DMU: White crystals (1.12 g, 4.00 mmol, 8%, Rf = 0.18 (EtOAc)).1H-NMR (400 MHz, CDCl3): δ 3.87 (d, J = 8.0 Hz, 2H), 3.62 (d, J = 8.0 Hz, 2H), 3.25 (s, 6H), 3.06 ppm (s, 6H). 13C {1H}-NMR (101 MHz, CDCl3): δ 168.1 (2C), 151.8 (2C), 59.3 (2C), 39.1 (2C), 35.1 (2C), 28.3 ppm (2C). HRMS (ESI) m/z calcd. for [C12H17N4O4]+: 281.1250 [M + H]+, found 281.1245.
- (c)
- c,a-DMU<>DMU: White crystals (0.56 g, 2.00 mmol, 4%, Rf = 0.08 (EtOAc)). 1H-NMR (400 MHz, CDCl3): δ 4.09 (t, J = 8.5 Hz, 2H), 3.77 (t, J = 8.6 Hz, 2H), 3.12 (s, 6H), 3.11 ppm (s, 6H). 13C {1H}-NMR (101 MHz, CDCl3): δ 166.1 (2C), 152.2 (2C), 49.3 (2C), 45.4 (2C), 35.7 (2C), 27.8 ppm (2C). HRMS (ESI) m/z calcd. for [C12H17N4O4]+: 281.1250 [M + H]+, found 281.1245.
- (d)
- c,s-DMU<>DMU: White crystals (1.54 g, 5.49 mmol, 11%, Rf = 0.04 (EtOAc)). 1H-NMR (400 MHz, CDCl3): δ 4.06 (dd, J = 6.1, 3.9 Hz, 2H), 3.78 (dd, J = 6.1, 3.9 Hz, 2H), 3.16 (s, 6H), 3.00 ppm (s, 6H). 13C {1H}-NMR (101 MHz, CDCl3): δ 165.8 (2C), 152.8 (2C), 55.5 (2C), 39.6 (2C), 35.7 (2C), 28.0 ppm (2C). HRMS (ESI) m/z calcd. for [C12H17N4O4]+: 281.1250 [M + H]+, found 281.1245.
Synthesis of DMT<>DMT Isomers
- (a)
- c,a-DMT<>DMT: White crystals (0.70 g, 2.27 mmol, 7%, Rf = 0.04 (1:1 n-pentane/EtOAc)). 1H-NMR (400 MHz, CDCl3): δ 3.27 (s, 2H), 3.16 (s, 6H), 3.08 (s, 6H), 1.58 ppm (s, 6H). 13C {1H}-NMR (101 MHz, CDCl3): δ 169.6 (2C), 151.9 (2C), 64.4 (2C), 48.8 (2C), 36.3 (2C), 27.9 (2C), 25.0 ppm (2C). HRMS (ESI) m/z calcd. for [C14H21N4O4]+: 309.1563 [M + H]+, found 309.1557.
- (b)
- c,s-DMT<>DMT: White crystals (2.03 g, 6.58 mmol, 22%, Rf = 0.10 (EtOAc)). 1H-NMR (500 MHz, CDCl3): δ 3.72 (s, 2H), 3.14 (s, 6H), 3.00 (s, 6H), 1.50 ppm (s, 6H). 13C {1H}-NMR (126 MHz, CDCl3): δ 169.5 (2C), 152.5 (2C), 60.6 (2C), 47.6 (2C), 35.9 (2C), 28.3 (2C), 19.4 ppm (2C). HRMS (ESI) m/z calcd. for [C14H21N4O4]+: 309.1563 [M + H]+, found 309.1582.
Synthesis of DMU6-Me<>DMU6-Me Isomers
- (a)
- t,s-DMU6-Me<>DMU6-Me: White crystals (0.21 g, 0.67 mmol, 3%, Rf = 0.05 (1:1 n-pentane/EtOAc)). 1H-NMR (400 MHz, CDCl3): δ 3.27 (s, 6H), 3.23 (s, 2H), 3.00 (s, 6H), 1.42 ppm (s, 6H). 13C {1H}-NMR (101 MHz, CDCl3): δ 168.1 (2C), 152.4 (2C), 62.2 (2C), 45.1 (2C), 31.2 (2C), 28.5 (2C), 22.3 ppm (2C). HRMS (ESI) m/z calcd. for [C14H21N4O4]+: 309.1563 [M + H]+, found 309.1556.
- (b)
- c,a-DMU6-Me<>DMU6-Me: White crystals (4.11 g, 13.30 mmol, 53%, Rf = 0.19 (EtOAc)). 1H-NMR (400 MHz, CDCl3): δ 3.21 (s, 6H), 3.16 (s, 2H), 2.82 (s, 6H), 1.65 ppm (s, 6H). 13C {1H}-NMR (101 MHz, CDCl3): δ 165.3 (2C), 152.0 (2C), 58.0 (2C), 53.6 (2C), 31.2 (2C), 28.2 (2C), 27.8 ppm (2C). HRMS (ESI) m/z calcd. for [C14H21N4O4]+: 309.1563 [M + H]+, found 309.1557.
- (c)
- c,s-DMU6-Me<>DMU6-Me: White crystals (0.82 g, 2.67 mmol, 11%, Rf = 0.03 (2:1 n-pentane/EtOAc)). 1H-NMR (400 MHz, CDCl3): δ 3.41 (s, 2H), 3.16 (s, 6H), 2.92 (s, 6H), 1.52 ppm (s, 6H). 13C {1H}-NMR (101 MHz, CDCl3): δ 165.6 (2C), 152.8 (2C), 62.5 (2C), 44.9 (2C), 32.2 (2C), 28.0 (2C), 21.6 ppm (2C). HRMS (ESI) m/z calcd. for [C14H21N4O4]+: 309.1563 [M + H]+, found 309.1557.
2.2. X-ray Data
2.3. Laser Flash Photolysis Studies
2.4. DFT Calculations
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References and Notes
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Entry | Dimer(s) 1 | E0 2 | Products 3 |
Product Studies 4 | |||
1 5 | c,s-DMU<>DMU | 1.825 | c,s-DMU<>DMU (7%), DMU (50%), 1 (33%) |
2 5 | t,s-DMU<>DMU | 1.850 | t,s-DMU<>DMU (37%), DMU (14%), 1 (35%) |
3 5 | c,a-DMU<>DMU | ≈2.195 | c,a-DMU<>DMU (39%), DMU (33%) |
4 5 | t,a-DMU<>DMU | t,a-DMU<>DMU (30%), DMU (34%) | |
5 | c,s-DMT<>DMT | 1.815 | c,s-DMT<>DMT (48%), DMT (48%) |
6 | c,a-DMT<>DMT | c,a-DMT<>DMT (58%), DMT (25%) | |
7 | c,s-DMU6-Me<>DMU6-Me | c,s-DMU6-Me<>DMU6-Me (22%), DMU6-Me (73%) | |
Competition Studies 6 | |||
8 | c,s-DMU<>DMU + t,s-DMU<>DMU | c,s-DMU<>DMU (76%), t,s-DMU<>DMU (24%) | |
9 | c,a-DMU<>DMU + t,a-DMU<>DMU | c,a-DMU<>DMU (60%), t,a-DMU<>DMU (40%) | |
10 | c,s-DMT<>DMT + c,a-DMT<>DMT | c,s-DMT<>DMT (19%), c,a-DMT<>DMT (81%) | |
11 | c,s-DMU<>DMU + c,s-DMT<>DMT | c,s-DMU<>DMU (29%), c,s-DMT<>DMT (71%) | |
12 | c,s-DMU<>DMU + c,s- DMU6-Me<>DMU6-Me | c,s-DMU<>DMU (8%), c,s- DMU6-Me<>DMU6-Me (92%) | |
13 | c,s-DMT<>DMT + c,s- DMU6-Me<>DMU6-Me | c,s-DMT<>DMT (31%), c,s- DMU6-Me<>DMU6-Me (69%) |
Entry | Dimer | k/M−1 s−1 | Monomer: k/M−1 s−1 |
---|---|---|---|
1 | t,s-DMU<>DMU | 2.8 × 109 | DMU: 1.0 × 109 |
2 | c,s-DMU<>DMU | 9.0 × 108 | |
3 | t,a-DMU<>DMU | 5.5 × 108 | |
4 | c,a-DMU<>DMU | 3.1 × 108 | |
5 | c,s-DMT<>DMT | 1.2 × 109 | DMT: 6.3 × 109 |
6 | c,a-DMT<>DMT | 5.2 × 108 | |
7 | t,s-DMU6-Me<>DMU6-Me | 5.7 × 108 | DMU6-Me: 4.8 × 109 |
8 | c,s-DMU6-Me<>DMU6-Me | 3.9 × 108 | |
9 | c,a-DMU6-Me<>DMU6-Me | 8.0 × 107 |
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Haddad, T.; Nathanael, J.G.; White, J.M.; Wille, U. Oxidative Repair of Pyrimidine Cyclobutane Dimers by Nitrate Radicals (NO3•): A Kinetic and Computational Study. Chemistry 2020, 2, 453-469. https://doi.org/10.3390/chemistry2020027
Haddad T, Nathanael JG, White JM, Wille U. Oxidative Repair of Pyrimidine Cyclobutane Dimers by Nitrate Radicals (NO3•): A Kinetic and Computational Study. Chemistry. 2020; 2(2):453-469. https://doi.org/10.3390/chemistry2020027
Chicago/Turabian StyleHaddad, Tomas, Joses G. Nathanael, Jonathan M. White, and Uta Wille. 2020. "Oxidative Repair of Pyrimidine Cyclobutane Dimers by Nitrate Radicals (NO3•): A Kinetic and Computational Study" Chemistry 2, no. 2: 453-469. https://doi.org/10.3390/chemistry2020027