Factors Governing the Chemical Stability and NMR Parameters of Uracil Tautomers and Its 5-Halogen Derivatives
Abstract
:1. Introduction
2. Results and Discussion
2.1. Energy of Uracil Tautomers and Its Derivatives
2.2. Aromaticity of Uracil, 5XU and Their Tautomers
2.3. Chemical Shifts and Indirect Spin-Spin Coupling Constants of Uracil and 5-Fluorouracil
3. Methods
3.1. Computational Methods
3.2. NMR Experiment
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available. |
ΔE | μ | |||||
---|---|---|---|---|---|---|
Tautomer | Vacuum | PCM | SMD | Vacuum | PCM | SMD |
U1 a | 0.00 | 0.00 | 0.00 | 4.46 | 6.12 | 6.93 |
U2 | 12.07 | 11.42 | 9.54 | 4.88 | 6.95 | 7.84 |
U3 | 21.19 | 18.27 | 15.24 | 7.17 | 10.26 | 11.62 |
U4 | 19.63 | 16.76 | 14.08 | 6.56 | 9.56 | 10.83 |
U5 | 11.61 | 14.32 | 12.95 | 3.31 | 4.63 | 5.45 |
U6 | 13.73 | 18.86 | 17.14 | 1.19 | 1.68 | 1.82 |
5FU1 b | 0.00 | 0.00 | 0.00 | 4.10 | 5.74 | 6.49 |
5FU2 | 12.90 | 12.61 | 10.57 | 3.60 | 5.27 | 6.01 |
5FU3 | 20.46 | 19.64 | 16.83 | 5.85 | 8.54 | 9.76 |
5FU4 | 17.06 | 14.27 | 11.69 | 7.02 | 10.22 | 11.57 |
5FU5 | 9.64 | 12.30 | 10.96 | 4.33 | 6.02 | 6.88 |
5FU6 | 12.46 | 17.93 | 16.04 | 0.60 | 0.63 | 0.68 |
5ClU1 c | 0.00 | 0.00 | 0.00 | 4.02 | 5.75 | 6.49 |
5ClU2 | 12.53 | 12.32 | 10.43 | 3.58 | 5.22 | 5.87 |
5ClU3 | 18.32 | 18.10 | 16.37 | 5.71 | 8.40 | 9.45 |
5ClU4 | 17.86 | 15.05 | 12.57 | 6.87 | 10.17 | 11.50 |
5ClU5 | 10.08 | 12.57 | 11.20 | 4.28 | 6.12 | 7.03 |
5ClU6 | 12.54 | 17.95 | 16.17 | 0.61 | 0.73 | 0.84 |
5BrU1 d | 0.00 | 0.00 | 0.00 | 3.97 | 5.74 | 6.32 |
5BrU2 | 12.44 | 12.22 | 10.08 | 3.62 | 5.32 | 5.86 |
5BrU3 | 18.02 | 17.90 | 17.05 | 5.77 | 8.51 | 9.22 |
5BrU4 | 17.97 | 15.17 | 12.73 | 6.77 | 10.10 | 11.22 |
5BrU5 | 10.18 | 12.65 | 11.20 | 4.20 | 6.04 | 6.80 |
5BrU6 | 12.58 | 17.95 | 15.80 | 0.55 | 0.67 | 0.72 |
5IU1 e | 0.00 | 0.00 | 0.00 | 3.91 | 5.36 | 6.11 |
5IU2 | 13.89 | 13.41 | 11.30 | 3.42 | 4.73 | 5.75 |
5IU3 | 20.22 | 20.00 | 16.33 | 5.69 | 7.95 | 9.44 |
5IU4 | 20.17 | 17.12 | 14.60 | 6.68 | 9.40 | 10.49 |
5IU5 | 11.04 | 12.99 | 11.83 | 4.29 | 5.87 | 6.35 |
5IU6 | 14.28 | 18.52 | 16.57 | 0.75 | 0.86 | 0.69 |
Molecule | Vacuum | Water | ||||||
---|---|---|---|---|---|---|---|---|
NICS (0) | NICS (1) | NICS (1)zz | HOMA | NICS (0) | NICS (1) | NICS (1) zz | HOMA | |
U1 | −0.449 | −1.141 | −2.082 | 0.545 | −0.852 | −1.596 | −3.298 | 0.644 |
5FU1 | −2.354 | −1.680 | −2.150 | 0.526 | −2.763 | −2.101 | −3.213 | 0.603 |
5ClU1 | −1.324 | −1.435 | −1.773 | 0.469 | −1.661 | −1.821 | −2.776 | 0.602 |
5BrU1 | −1.071 | −1.360 | −1.515 | 0.472 | −1.400 | −1.744 | −2.518 | 0.604 |
5IU1 a | −0.732 | −1.269 | −1.287 | 0.504 | −1.053 | −1.653 | −2.303 | 0.609 |
1,2-diazine | −4.924 | −10.269 | −29.170 | 0.975 | −4.895 | −10.231 | −29.117 | 0.969 |
pyrimidine | −5.281 | −9.781 | −28.236 | 0.992 | −5.253 | −9.780 | −28.252 | 0.991 |
1,4-diazine | −5.001 | −10.088 | −29.374 | 0.997 | −4.962 | −10.077 | −29.353 | 0.997 |
pyridine | −6.579 | −10.007 | −29.470 | 0.993 | −6.546 | −9.999 | −29.472 | 0.993 |
benzene | −7.828 | −10.014 | −30.041 | 0.991 | −7.774 | −10.000 | −30.016 | 0.994 |
B3LYP | xOPBE | ||||||||
---|---|---|---|---|---|---|---|---|---|
STO(1M)−3G | aug-cc-pVQZ | STO(1M)−3G | aug-cc-pVQZ | ||||||
Signal | Exp. | Vacuum | Water | Vacuum | Water | Vacuum | Water | Vacuum | Water |
C2 | 155.93 b | −4.61 | −2.96 | −7.26 | −5.01 | −4.86 | −3.48 | −8.95 | −7.02 |
C4 | 170.30 b | −7.12 | −4.01 | −8.81 | −4.89 | −8.15 | −5.45 | −11.15 | −7.71 |
C5 | 103.79 b | −1.12 | −2.99 | −2.96 | −4.80 | −0.07 | −1.93 | −2.16 | −4.02 |
C6 | 146.26 b | −7.12 | −2.83 | −7.83 | −2.82 | −6.75 | −2.76 | −7.89 | −3.23 |
H5 | 5.79 b | −0.94 | −1.00 | −0.62 | −0.64 | −1.04 | −1.10 | −0.66 | −0.68 |
H6 | 7.53 b | −0.62 | −0.33 | −0.93 | −0.62 | −0.67 | −0.38 | −1.00 | −0.70 |
N1 | −248.81 c | 17.27 | 24.11 | 19.60 | 27.89 | 8.65 | 15.21 | 11.27 | 19.18 |
N3 | −221.35 c | 22.98 | 24.57 | 26.71 | 29.62 | 13.09 | 14.62 | 16.67 | 19.49 |
O2 | 252.5 c | 12.36 | −6.83 | 34.50 | 12.78 | −6.22 | −23.02 | 21.21 | 2.22 |
O4 | 334 c | 20.71 | −17.07 | 53.71 | 10.36 | −2.45 | −36.48 | 36.81 | −1.95 |
RMS (C) | 5.56 | 3.23 | 7.08 | 4.47 | 5.82 | 3.65 | 8.24 | 5.82 | |
RMS (C, H) | 4.57 | 2.67 | 5.80 | 3.67 | 4.78 | 3.01 | 6.74 | 4.76 | |
RMS (N, O) | 18.76 | 19.52 | 35.96 | 21.94 | 8.53 | 24.01 | 23.50 | 13.75 |
B3LYP | xOPBE | ||||||||
---|---|---|---|---|---|---|---|---|---|
STO(1M)−3G | aug-cc-pVQZ | STO(1M)−3G | aug-cc-pVQZ | ||||||
Signal | Exp. | Vacuum | Water | Vacuum | Water | Vacuum | Water | Vacuum | Water |
C2 | 152.19 b | −1.97 | −0.52 | −5.08 | −3.11 | −2.24 | −1.06 | −6.77 | −5.11 |
C4 | 160.98 b | −2.65 | −0.25 | −5.50 | −2.41 | −3.19 | −1.17 | −7.23 | −4.58 |
C5 | 141.30 b | 4.57 | 3.17 | 3.48 | 2.24 | 3.47 | 2.03 | 1.46 | 0.17 |
C6 | 127.54 b | −1.41 | 2.88 | −4.64 | 0.39 | −0.53 | 3.43 | −4.44 | 0.22 |
H6 | 7.65 b | −0.72 | −0.38 | −1.06 | −0.69 | −0.83 | −0.50 | −1.19 | −0.84 |
N1 | −261.06 c | 16.12 | 24.61 | 17.19 | 27.30 | 8.13 | 16.19 | 9.48 | 19.03 |
N3 | −221.55 c | 22.23 | 23.77 | 26.01 | 28.92 | 12.56 | 14.02 | 16.27 | 19.09 |
O2 | 250 c | 12.91 | −4.42 | 34.00 | 14.28 | −5.98 | −21.16 | 20.30 | 3.04 |
O4 | 321.3 c | 23.08 | −15.25 | 56.15 | 12.76 | 0.22 | −34.53 | 39.51 | 0.46 |
F | −169.31 d | 3.76 | −2.51 | −14.60 | −21.87 | 11.59 | 5.39 | −2.49 | −9.59 |
RMS (C) | 2.90 | 2.16 | 4.74 | 2.27 | 2.62 | 2.14 | 5.48 | 3.43 | |
RMS (C, H) | 2.62 | 1.94 | 4.26 | 2.06 | 2.37 | 1.93 | 4.93 | 3.09 | |
RMS (N, O, F) | 17.13 | 16.91 | 33.15 | 22.03 | 8.88 | 20.63 | 21.60 | 12.87 |
B3LYP | xOPBE | ||||||||
---|---|---|---|---|---|---|---|---|---|
STO(1M)−3G | aug-cc-pVQZ | STO(1M)−3G | aug-cc-pVQZ | ||||||
SSCC | Exp. | Vacuum | Water | Vacuum | Water | Vacuum | Water | Vacuum | Water |
1J (C5H5) | 177.83 | −21.71 | −21.00 | 7.21 | 8.06 | −40.33 | −39.74 | −13.44 | −12.76 |
1J (C6H6) | 183.82 | −29.47 | −23.13 | −0.92 | 6.65 | −47.55 | −41.64 | −20.78 | −13.74 |
2J (C5H6) | 2.96 | −0.82 | −0.43 | 0.05 | 0.48 | −2.14 | −1.73 | −1.97 | −1.50 |
3J (C2H6) | 9.42 | −1.72 | −1.46 | −0.13 | 0.16 | −2.23 | −1.94 | −0.75 | −0.38 |
3J (C4H6) | 10.54 | −1.22 | −1.24 | 0.57 | 0.56 | −1.21 | −1.26 | 0.67 | 0.61 |
3J (H5H6) | 7.69 | 1.01 | 0.95 | 1.65 | 1.59 | 0.62 | 0.53 | 1.37 | 1.27 |
2J (H5C6) | 3.64 | 0.77 | 0.45 | 2.07 | 1.64 | −1.13 | −1.40 | −0.62 | −0.94 |
2J (H5C4) | 1.79 | −0.21 | 0.23 | 0.29 | 0.82 | −2.02 | −1.58 | −2.04 | −1.50 |
RMS | 12.97 | 11.07 | 2.75 | 3.80 | 22.09 | 20.39 | 8.83 | 6.70 | |
RMS c | 11.17 | 8.78 | 1.09 | 2.69 | 18.04 | 15.80 | 7.96 | 5.30 |
B3LYP | xOPBE | ||||||||
---|---|---|---|---|---|---|---|---|---|
STO(1M)−3G | aug-cc-pVQZ | STO(1M)−3G | aug-cc-pVQZ | ||||||
SSCC | Exp. | Vacuum | Water | Vacuum | Water | Vacuum | Water | Vacuum | Water |
1J (C5F5) | 227.0 | 8.74 | −4.57 | 86.09 | 69.64 | 10.58 | −1.12 | 88.60 | 73.41 |
1J (C6H6) | 182.0 | −26.54 | −20.91 | 2.37 | 8.86 | −45.06 | −39.80 | −18.13 | −11.88 |
2J (C5H6) | 4.1 | 0.28 | 0.16 | 0.79 | 0.65 | 1.63 | 1.48 | 2.69 | 2.41 |
3J (C2H6) | 10.1 | −2.33 | −2.12 | −0.74 | −0.47 | −2.86 | −2.62 | −1.39 | −1.08 |
3J (C4H6) | 7.3 | −1.25 | −1.30 | −0.03 | 0.01 | −0.97 | −1.05 | 0.34 | 0.25 |
3J (F5H6) | 6.0 | 2.09 | 0.87 | −1.90 | −0.53 | 4.30 | 3.25 | −6.22 | −4.86 |
2J (F5C6) | 31.1 | 7.49 | 6.79 | 1.74 | 2.28 | 11.82 | 11.06 | −3.01 | −0.47 |
2J (F5C4) | 25.6 | 7.12 | 8.18 | −0.22 | −1.66 | 9.02 | 9.95 | −2.23 | −3.50 |
RMS | 10.60 | 8.50 | 30.46 | 24.84 | 17.30 | 15.11 | 32.09 | 26.39 | |
RMS c | 10.84 | 8.92 | 1.39 | 3.53 | 18.05 | 16.15 | 7.47 | 5.13 |
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Rzepiela, K.; Buczek, A.; Kupka, T.; Broda, M.A. Factors Governing the Chemical Stability and NMR Parameters of Uracil Tautomers and Its 5-Halogen Derivatives. Molecules 2020, 25, 3931. https://doi.org/10.3390/molecules25173931
Rzepiela K, Buczek A, Kupka T, Broda MA. Factors Governing the Chemical Stability and NMR Parameters of Uracil Tautomers and Its 5-Halogen Derivatives. Molecules. 2020; 25(17):3931. https://doi.org/10.3390/molecules25173931
Chicago/Turabian StyleRzepiela, Kacper, Aneta Buczek, Teobald Kupka, and Małgorzata A. Broda. 2020. "Factors Governing the Chemical Stability and NMR Parameters of Uracil Tautomers and Its 5-Halogen Derivatives" Molecules 25, no. 17: 3931. https://doi.org/10.3390/molecules25173931
APA StyleRzepiela, K., Buczek, A., Kupka, T., & Broda, M. A. (2020). Factors Governing the Chemical Stability and NMR Parameters of Uracil Tautomers and Its 5-Halogen Derivatives. Molecules, 25(17), 3931. https://doi.org/10.3390/molecules25173931