Theoretical study on the aging and reactivation mechanism of tabun-inhibited acetylcholinesterase by using the quantum mechanical / molecular mechanical method
Bibliographic record
Abstract
The organophosphorous compound tabun is highly neurotoxic because of its irreversible inhibition on acetylcholinesterase (AChE). It is wildly used as a warfare agent in the military. In this work, the aging and reactivation mechanism of tabun-inhibited AChE were studied by using the quantum mechanical / molecular mechanical (QM/MM) method. Geometry optimization of the stationary points were performed at the B3LYP/6–31G(d) level. Single-point energies were computed at the B3LYP/6–311++G(d,p) level. On the basis of the QM/MM results, a conclusion that the C–O bond scission is caused by water attack on the ethoxy group in the aging mechanism can be drawn. The reactivation process initialed by the antidotes CH 2 NO – or HLÖ-7 consists of three elemental steps, the nucleophilic attack on the P atom by the antidote, the dephosphorylation process, and the decomposition of the antidote–tabun complex. The highest energy barriers of the aging reaction, CH 2 NO – -induced reactivation, and HLÖ-7-induced reactivation are 19.9, 20.0, and 14.8 kcal/mol (1 cal = 4.184 J), respectively. The relative lower overall energy barrier of HLÖ-7-induced reactivation compared with that of the aging reaction indicates that HLÖ-7 is able to reactivate tabun-inhibited AChE. In addition, whether a newly designed antidote is able to reactivate tabun-inhibited AChE can be examined by the inequation X < 19.9 kcal/mol,where X means the highest energy barrier of the reactivation reaction of the newly designed antidote.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".