Theoretical Study of Hydroxylation of α- and β-Pinene by a Cytochrome P450 Monooxygenase Model
Abstract
:1. Introduction
2. Results and Discussion
2.1. Alpha- and Beta-Pinene Bare Systems
2.2. CYP Monooxygenase Model
2.3. R and S Enantiomers Cis/Trans Reaction
2.4. CYP-Catalyzed Hydroxylation of β-Pinene
2.5. CYP-Catalyzed Hydroxylation of α-Pinene
3. Materials and Methods
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Radical | Gcor(Eh) | Gcor(ref) (kcal/mol) | Hydroxylated Product | Gcor(Eh) | Gcor(ref) (kcal/mol) | |
---|---|---|---|---|---|---|
Alpha | −389.788789 | 21.7 | Alpha | −465.658506 | 1.4 | |
Gamma | −389.819706 | 2.27 | Gamma | −465.645667 | 9.45 | |
Delta | −389.777607 | 28.7 | Delta | −465.660286 | 0.28 | |
Epsilon | −389.823321 | 0 | Epsilon cis | −465.651306 | 5.91 | |
Epsilon trans | −465.652273 | 5.31 | ||||
Zeta | −389.790994 | 20.3 | Zeta | −465.660730 | 0.00 | |
Theta | −389.794206 | 18.3 | Theta | −465.654240 | 4.07 | |
Iota | −389.795916 | 17.2 | Iota | −465.646394 | 9 | |
Kappa | −389.796285 | 17 | Kappa | −465.646120 | 9.17 |
Radical | Gcor (Eh) | Gcor(ref) (kcal/mol) | Hydroxylated Product | Gcor (Eh) | Gcor(ref) (kcal/mol) | |
---|---|---|---|---|---|---|
Alpha | −389.784833 | 21.9 | Alpha | −465.653831 | 0.57 | |
Gamma | −389.770224 | 31.1 | Gamma | −465.649621 | 3.21 | |
Delta | −389.819707 | 0 | Delta cis | −465.645132 | 6.03 | |
Delta trans | −465.644727 | 6.28 | ||||
Epsilon | −389.797584 | 13.9 | Epsilon cis | −465.6451796 | 6.00 | |
Epsilon trans | −465.6473512 | 4.63 | ||||
Zeta | −389.786313 | 20.9 | Zeta | −465.6547380 | 0 | |
Theta | −389.788711 | 19.4 | Theta | −465.6488230 | 3.71 | |
Iota | −389.789920 | 18.7 | Iota | −465.6375598 | 10.78 | |
Kappa | −389.790510 | 18.3 | Kappa | −465.6399752 | 9.26 |
RC | Site | Spin | Gref (kcal/mol) | RC | Site | Spin | Gref (kcal/mol) |
---|---|---|---|---|---|---|---|
1 | Epsilon cis-(S) | S = 1/2 | 2.41 | 1 | Epsilon cis-(R) | S = 1/2 | 2.40 |
2 | 11.4 | 2 | 11.4 | ||||
3 | −12.6 | 3 | −12.6 | ||||
1 | Epsilon trans-(S) | S = 1/2 | 0.184 | 1 | Epsilon trans-(R) | S = 1/2 | 0.184 |
2 | 12.4 | 2 | 12.4 | ||||
3 | −13.7 | 3 | −13.7 |
Site | Spin | ΔrE | ΔE‡ | ΔrH | ΔH‡ | ΔrG | ΔG‡ | ΔrGcor | ΔG‡cor | HydΔrGcor |
---|---|---|---|---|---|---|---|---|---|---|
Delta cis-(R) | S = 1/2 | −4.11 | 17.4 | −6.13 | 12.8 | −3.82 | 17.6 | −7.05 | 12.4 | −47.4 |
Delta trans-(S) | S = 1/2 | −4.64 | 15.4 | −5.56 | 10.9 | −5.10 | 15.4 | −8.30 | 10.8 | −48.4 |
Delta cis-(R) | S = 3/2 | −0.183 | 18.7 | −1.59 | 13.8 | −0.548 | 18.8 | −2.64 | 13.6 | −45.6 |
Delta trans-(S) | S = 3/2 | −1.03 | 16.5 | −1.16 | 13.0 | −3.67 | 13.4 | −5.08 | 9.87 | −47.3 |
Delta cis-(R) | S = 5/2 | −6.52 | 19.6 | −7.19 | 15.9 | −13.3 | 15.8 | −9.18 | 12.8 | −54.0 |
Delta trans-(S) | S = 5/2 | −7.36 | 17.3 | −7.35 | 14.4 | −15.1 | 12.5 | −11.5 | 10.1 | −54.2 |
Alpha | S = 1/2 | +17.4 | 21.5 | +15.4 | 16.8 | +18.9 | 22.2 | +17.4 | 15.3 | −50.0 |
Alpha | S = 3/2 | +13.0 | 18.8 | +13.6 | 15.3 | +14.3 | 18.5 | +10.8 | 12.8 | −43.4 |
Reactant | G (hartree) | Mole Fraction | Population % | ΔrG | ΔG‡ |
---|---|---|---|---|---|
alpha-doublet | −1976.037587 | 0.49 | 48.77 | 28.1 | 15.3 |
alpha-quartet | −1976.030510 | 0 | 0.03 | 10.8 | 12.8 |
delta-trans-doublet | −1976.035861 | 0.08 | 7.83 | −8.3 | 10.8 |
delta-cis-doublet | −1976.036419 | 0.14 | 14.14 | −7.05 | 12.4 |
delta-cis-quartet | −1976.037104 | 0.29 | 29.23 | −2.64 | 13.6 |
delta-trans-quartet | −1976.014863 | 0 | 0 | −5.08 | 9.87 |
delta-cis-sextet | −1976.015837 | 0 | 0 | −9.18 | 12.8 |
delta-trans-sextet | −1976.014863 | 0 | 0 | −11.5 | 10.1 |
Reactant | G (hartree) | Mole Fraction | Population % | ΔrG | ΔG‡ |
---|---|---|---|---|---|
alpha-doublet | −1975.973971 | 0 | 0 | 28.1 | 15.3 |
alpha-quartet | −1975.973075 | 0 | 0 | 10.8 | 12.8 |
delta-trans-doublet | −1976.009716 | 0.534 | 53.4 | −8.3 | 10.8 |
delta-cis-doublet | −1976.009578 | 0.461 | 46.1 | −7.05 | 12.4 |
delta-cis-quartet | −1976.004151 | 0.00147 | 0.147 | −2.64 | 13.6 |
delta-trans-quartet | −1976.004891 | 0.00321 | 0.321 | −5.08 | 9.87 |
delta-cis-sextet | −1976.000132 | 0 | 0 | −9.18 | 12.8 |
delta-trans-sextet | −1976.001255 | 0 | 0 | −11.5 | 10.1 |
Site | Spin | ΔrE | ΔE‡ | ΔrH | ΔH‡ | ΔrG | ΔG‡ | ΔrGcor | ΔG‡cor | HydΔrGcor |
---|---|---|---|---|---|---|---|---|---|---|
Epsilon cis-(S) | S = 1/2 | −13.6 | 15.9 | −12.9 | 12.9 | −13.4 | 12.5 | −15.0 | 9.00 | −50.2 |
Epsilon trans-(R) | S = 1/2 | −14.8 | 14.6 | −14.8 | 11.0 | −10.5 | 16.6 | −13.8 | 12.2 | −48.9 |
Epsilon cis-(S) | S = 3/2 | −0.1 | 18.0 | −0.215 | 14.1 | −0.981 | 16.4 | −3.06 | 12.3 | −36.8 |
Epsilon trans-(R) | S = 3/2 | +0.814 | 16.7 | +0.413 | 12.7 | −1.10 | 15.0 | −1.87 | 11.2 | −37.9 |
Epsilon cis-(S) | S = 5/2 | −16.0 | 18.7 | −15.8 | 14.7 | −18.6 | 15.5 | −18.7 | 12.7 | −53.9 |
Epsilon trans-(R) | S = 5/2 | −15.7 | 17.5 | −16.8 | 13.0 | −14.1 | 17.3 | −15.2 | 13.2 | −53.9 |
Alpha | S = 1/2 | +18.4 | 22.8 | +18.0 | 18.7 | +18.3 | 21.4 | +14.8 | 15.9 | −50.2 |
Alpha | S = 3/2 | +16.7 | 24.9 | +15.9 | 20.6 | +15.7 | 23.1 | +13.5 | 18.1 | −37.1 |
Gamma | S = 1/2 | −3.18 | 16.1 | −4.05 | 12.5 | −0.516 | 16.9 | −5.73 | 12.6 | −41.9 |
Gamma | S = 3/2 | +1.09 | 18.0 | +0.612 | 14.0 | +0.437 | 15.8 | −1.80 | 14.2 | −30.8 |
Reactant | G (hartree) | Mole Fraction | Population % | ΔrG | ΔG‡ |
---|---|---|---|---|---|
alpha-doublet | −1976.041937 | 0.0871 | 8.71 | 14.8 | 17.6 |
alpha-quartet | −1976.024096 | 0.209 | 20.9 | 13.5 | 18.1 |
epsilon-trans-doublet | −1976.042897 | 0.241 | 24.1 | −13.8 | 12.2 |
epsilon-cis-doublet | −1976.039343 | 0.00557 | 0.557 | −15.0 | 8.99 |
epsilon-trans-quartet | −1976.040800 | 0.0261 | 2.61 | −1.87 | 11.2 |
epsilon-cis-quartet | −1976.041490 | 0.0542 | 5.42 | −3.06 | 12.3 |
epsilon-trans-sextet | −1976.024055 | 0 | 0 | −15.2 | 13.2 |
epsilon-cis-sextet | −1976.022164 | 0 | 0 | −18.7 | 12.7 |
gamma-doublet | −1976.043191 | 0.329 | 32.9 | −5.73 | 12.6 |
gamma-quartet | −1976.041393 | 0.0489 | 4.89 | −1.80 | 14.2 |
Reactant | G (hartree) | Mole Fraction | Population % | ΔrG | ΔG‡ |
---|---|---|---|---|---|
alpha-doublet | −1976.018408 | 0 | 0 | 14.8 | 17.6 |
alpha-quartet | −1976.021248 | 0 | 0 | 13.5 | 18.1 |
epsilon-trans-doublet | −1976.064967 | 0.864 | 86.4 | −13.8 | 12.2 |
epsilon-cis-doublet | −1976.063223 | 0.136 | 13.6 | −15.0 | 8.99 |
epsilon-trans-quartet | −1976.043787 | 0 | 0 | −1.87 | 11.2 |
epsilon-cis-quartet | −1976.046371 | 0 | 0 | −3.06 | 12.3 |
epsilon-trans-sextet | −1976.048297 | 0 | 0 | −15.2 | 13.2 |
epsilon-cis-sextet | −1976.051903 | 0 | 0 | −18.7 | 12.7 |
gamma-doublet | −1976.052329 | 0 | 0 | −5.73 | 12.6 |
gamma-quartet | −1976.044266 | 0 | 0 | −1.80 | 14.2 |
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Shaya, J.; Aloum, L.; Lu, C.-S.; Corridon, P.R.; Aoudi, A.; Shunnar, A.; Alefishat, E.; Petroianu, G. Theoretical Study of Hydroxylation of α- and β-Pinene by a Cytochrome P450 Monooxygenase Model. Int. J. Mol. Sci. 2023, 24, 5150. https://doi.org/10.3390/ijms24065150
Shaya J, Aloum L, Lu C-S, Corridon PR, Aoudi A, Shunnar A, Alefishat E, Petroianu G. Theoretical Study of Hydroxylation of α- and β-Pinene by a Cytochrome P450 Monooxygenase Model. International Journal of Molecular Sciences. 2023; 24(6):5150. https://doi.org/10.3390/ijms24065150
Chicago/Turabian StyleShaya, Janah, Lujain Aloum, Chung-Shin Lu, Peter R. Corridon, Abdulrahman Aoudi, Abeer Shunnar, Eman Alefishat, and Georg Petroianu. 2023. "Theoretical Study of Hydroxylation of α- and β-Pinene by a Cytochrome P450 Monooxygenase Model" International Journal of Molecular Sciences 24, no. 6: 5150. https://doi.org/10.3390/ijms24065150