XVIth International Workshop on
Quantum Systems in
Chemistry and Physics
QSCP logo Abstract
 Main | Registration | Abstract Submission | List of Registrants | List of Abstracts | Program 
Accommodation | Location and Access | Previous Workshops | ISTCP-VII | Photos
Oral presentations only. Posters only. Show all.

Computational study of conformational preferences in intermediates and transition states of the hydrolysis of dimethyl phosphate
Makoto Kita,1 Haruki Nakamura1 and Yu Takano1
1Institute for Protein Research, Osaka University, Japan
Phosphate diester is a basic structure in DNA and RNA. Hydrolysis mechanism of phosphate diester is important for understanding decomposition reaction of nucleic acid.
In this study, we have explored the hydrolysis reaction pathway of dimethyl phosphate, which is the simplest phosphate diester, with two nucleophiles (hydroxide and water), using the density functional theory (B3LYP/6-311++G(2d,2p)) with PCM (polarizable-continuum model). Since it was reported that the conformations of intermediates and transition states influence the reaction mechanism of transacylation of methyl acetate with methoxide [1], we focused on the conformational preferences in the hydrolysis reaction. The computed reaction pathway was confirmed by IRC (intrinsic reaction coordinate) calculation.
In hydrolysis of dimethyl phosphate with hydroxide, a concerted reaction pathway was obtained in the gas phase, whereas a stepwise reaction pathway was obtained in the aqueous phase. In the gas phase, the conformation of the transition state was different from that of the earlier study [2], but the reaction mechanism was similar to each other. The conformations hardly influence the energetics of the gas-phase hydrolysis of dimethyl phosphate. On the other hand, in the aqueous phase, the reaction pathway and the activation and reaction energies were very different from those of the earlier study [2], due to the differences in the computational procedure.
We have also explored the reaction mechanism of the hydrolysis of dimethyl phosphate with water. In the gas phase, the most stable conformation of the reactant (conf1) changed to the other conformation (conf2). The reaction proceeded with conf2, and the stepwise reaction pathway was obtained. This is because the activation energy of the hydrolysis of conf2 is lower than that of conf1, and because the activation energy of conformational change from conf1 to conf2 is as low as 2.2 kcal/mol. In the aqueous phase, the proton transfer, the first step of hydrolysis, did not occur, implying that the hydrolysis occurs by a proton shuttle mechanism.


References
[1] Takano, Y.; Houk, N. K. J. Phys. Chem. A 2004, 108(52), 11740-11751.
[2] Ribeiro, J. M. A.; Ramos, J. M.; Fernandes, A. P. J. Chem. Theory Comput. 2010, 6(8), 2281-2292.


 Main | Registration | Abstract Submission | List of Registrants | List of Abstracts | Program 
Accommodation | Location and Access | Previous Workshops | ISTCP-VII | Photos