Computational Modeling of the Dehydrogenation of Methylamine

Kirsten Ivey, Belynda Sanders, Chris Estela, and Andrew L. Cooksy*

Department of Chemistry and Biochemistry; San Diego State University; San Diego, CA 92182–1030. *corresponding author; Department of Chemistry and Biochemistry; San Diego State University; San Diego, CA 92182–1030; e–mail: acooksy@sciences.sdsu.edu; tel: +1–619–594–5571.

Received June 14, 2010.
Accepted October 12, 2010.

Abstract

The reaction sequence early in the metabolism of methyl–amine by the dehydrogenase cofactor tryptophan tryptophyl quinone (TTQ) is investigated by a large series of density functional theory calculations. Free energy corrections are calculated at the reactant and intermediate geometries, and solvation effects are estimated by use of the semi–empirical COSMO–RS solvent model. Two competing reaction paths are found to have very similar reaction free energies, and the free energies of activation are found to depend heavily on adequate modeling of the solvent.

Keywords: Tryptophan tryptophyl quinine; TTQ; density functional theory; COSMO–RS; solvent model.

Resumen

Se investigaron las reacciones tempranas en el metabolismo de la metilamina por el cofactor quinon–triptofil–triptofano (TTQ), mediante una larga serie de cálculos de la teoría de funcionales de la densidad. Las correcciones a las energías libres se calcularon en las geometrías del reactivo y de los intermediarios, así como los efectos del disolvente se estimaron por el modelo semi–empírico COSMO–RS. Se encontró que dos caminos de reacción compiten, teniendo energías libres de reacción muy similares, y las energías libres de activación dependen mucho de un modelado adecuado del disolvente.

Palabras clave: quinon–triptofil–triptofano; TTQ; teoría de funcionales de la densidad; COSMO–RS; modelo del disolvente.

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Acknowledgements

This work was originally supported by the Blasker Fund of the San Diego Foundation. Computer resources have been provided under US National Science Foundation Grant CHE–0216563. B. Sanders, C. Estela, and K. Ivey were supported by NIW fellowships from the US National Institutes of Health.

References

1. Backes, G.; Davidson, V. L.; Huitema, F.; Duine, J. A.; Sanders–Loehr, J. Biochemistry 1991, 30, 9201–9210.         [ Links ]

2. Davidson, V. L.; Kumar, M. A.; Wu, J. Biochemistry 1992, 31, 1504–1508.         [ Links ]

3. McIntire, W. S. FASEB J. 1994, 8, 513–21.         [ Links ]

4. Klinman, J. P.; Mu, D. Ann. Rev. Biochem. 1994, 63, 299–344.         [ Links ]

5. Pang, J.; Scrutton, N. S; de Visser, S. P.; Sutcliffe, M. J. J. Phys. Chem. A 2010, 114, 1212–1217.         [ Links ]

6. Masgrau, L.; Ranaghan, K. E.; Scrutton, N. S.; Mulholland, A. J.; Sutcliffe, M. J. J. Phys. Chem. B 2007, 111, 3032–3047.         [ Links ]

7. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, Jr., J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al–Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A.; Gaussian 03, Revision B.02, Gaussian, Inc., Pittsburgh PA, 2003.         [ Links ].

8. Eckert, F.; Klamt, A. AiCHE J. 2002, 48, 369–385.         [ Links ]

9. Becke, A. D. J. Chem. Phys. 1993, 98, 5648–5652.         [ Links ]

10. Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785–789.         [ Links ]

11. Dunning, J. T. H. J. Chem. Phys. 1989, 90, 1007–1023.         [ Links ]

12. Lui, R.; Cooksy, A. L. J. Comp. Theor. Chem. 2006, 2, 1395–1402.         [ Links ]

13. Klamt, A. J. Phys. Chem. 1995, 99, 2224–2235.         [ Links ]

14. Becke, A. D. Phys. Rev. A, 1988, 38, 3098–100.         [ Links ]

15. Perdew, J. P. Phys. Rev. B, 1986 33, 8822–8824.         [ Links ]

16. Schafer, A.; Huber, C.; Ahlrichs, R. J. Chem. Phys., 1994, 100, 5829–5835.         [ Links ]

17. Godbout, N.; Salahub, D. R.; Andzelm, J.; Wimmer, E. Can. J. Chem. 1992, 70, 560–571.         [ Links ]