|
|
|
|
| LEADER |
01000naa a22002652 4500 |
| 001 |
NLM176550275 |
| 003 |
DE-627 |
| 005 |
20231223144305.0 |
| 007 |
cr uuu---uuuuu |
| 008 |
231223s2008 xx |||||o 00| ||eng c |
| 028 |
5 |
2 |
|a pubmed24n0589.xml
|
| 035 |
|
|
|a (DE-627)NLM176550275
|
| 035 |
|
|
|a (NLM)18161688
|
| 040 |
|
|
|a DE-627
|b ger
|c DE-627
|e rakwb
|
| 041 |
|
|
|a eng
|
| 100 |
1 |
|
|a Wu, Yong
|e verfasserin
|4 aut
|
| 245 |
1 |
0 |
|a Theoretical study on the hydrolysis mechanism of N,N-dimethyl-N'-(2-oxo-1, 2-dihydro-pyrimidinyl)formamidine
|b water-assisted mechanism and cluster-continuum model
|
| 264 |
|
1 |
|c 2008
|
| 336 |
|
|
|a Text
|b txt
|2 rdacontent
|
| 337 |
|
|
|a ƒaComputermedien
|b c
|2 rdamedia
|
| 338 |
|
|
|a ƒa Online-Ressource
|b cr
|2 rdacarrier
|
| 500 |
|
|
|a Date Completed 03.06.2008
|
| 500 |
|
|
|a Date Revised 16.04.2008
|
| 500 |
|
|
|a published: Print
|
| 500 |
|
|
|a Citation Status PubMed-not-MEDLINE
|
| 520 |
|
|
|a The hydrolysis reaction of N,N-dimethyl-N'-(2-oxo-1, 2-dihydro-pyrimidinyl)formamidine (DMPFA), a model compound of the antivirus drug amidine-3TC (3TC = 2', 3'-dideoxy-3'-thiacytidine), is investigated by the hybrid density functional theory B3LYP/6-31+G (d,p) method. The hydrolysis reaction of the title compound is predicted to undergo via two pathways, each of which is a stepwise process. Path A is the addition of H2O to the C=N double bond in the amidine group to form a tetrahedral structure in its first step, and then the transfer of the H atom of hydroxyl leads to the corresponding products via four possible channels. Path B simultaneously involves the nucleophilic attack of H2O to the C atom of the C=N bond and the proton transfer to the N atom of amino group leading to the cleavage of the C-N single bond in the amidine group. The results indicate that path A is more favorable than path B in the gas phase. Moreover, to simulate the title reaction in aqueous solution, water-assisted mechanism and the cluster-continuum model, based on the SCRF/CPCM model, are taken into account in our work. The results indicate that it is rational for two water molecules served as a bridge to assist in the first step of path A and that cytosine rather than the cytosine-substituted formamide should be released from the tetrahedral intermediate via s six-membered cycle transition state (channel 2). Our calculations exhibit that the process toward the tetrahedral intermediate is the rate-determining step both in the gas phase and in aqueous solution
|
| 650 |
|
4 |
|a Journal Article
|
| 650 |
|
4 |
|a Research Support, Non-U.S. Gov't
|
| 700 |
1 |
|
|a Jin, Lu
|e verfasserin
|4 aut
|
| 700 |
1 |
|
|a Xue, Ying
|e verfasserin
|4 aut
|
| 700 |
1 |
|
|a Xie, Dai Qian
|e verfasserin
|4 aut
|
| 700 |
1 |
|
|a Kim, Chan Kyung
|e verfasserin
|4 aut
|
| 700 |
1 |
|
|a Guo, Yong
|e verfasserin
|4 aut
|
| 700 |
1 |
|
|a Yan, Guo Sen
|e verfasserin
|4 aut
|
| 773 |
0 |
8 |
|i Enthalten in
|t Journal of computational chemistry
|d 1984
|g 29(2008), 8 vom: 15. Juni, Seite 1222-32
|w (DE-627)NLM098138448
|x 1096-987X
|7 nnns
|
| 773 |
1 |
8 |
|g volume:29
|g year:2008
|g number:8
|g day:15
|g month:06
|g pages:1222-32
|
| 912 |
|
|
|a GBV_USEFLAG_A
|
| 912 |
|
|
|a SYSFLAG_A
|
| 912 |
|
|
|a GBV_NLM
|
| 912 |
|
|
|a GBV_ILN_350
|
| 951 |
|
|
|a AR
|
| 952 |
|
|
|d 29
|j 2008
|e 8
|b 15
|c 06
|h 1222-32
|