Quantum chemical calculations for understanding and predicting toxicity. II. The phosphorylation step in the inhibition of ache by organophosphorus anticholinesterases
| Autor: | Victor Lewchenko, P. C. Hariharan, Joyce J. Kaufman, Walter S. Koski |
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| Rok vydání: | 2009 |
| Předmět: |
Quantum chemical
Chemistry Aché Bond strength Aryl Condensed Matter Physics Acetylcholinesterase Atomic and Molecular Physics and Optics language.human_language Orders of magnitude (mass) chemistry.chemical_compound Computational chemistry Toxicity language Phosphorylation Physical and Theoretical Chemistry |
| Zdroj: | International Journal of Quantum Chemistry. 22:275-280 |
| ISSN: | 1097-461X 0020-7608 |
| Popis: | The first step in the inhibition of acetylcholinesterase (AChE) by organophosphorus anticholinesterases is formation of the organophosphorous molecule-AChE complex. In the first paper of this series it was shown that the first step can be modeled well by the use of three-dimensional electrostatic molecular potential contour maps around the P compound. The second phosphorylation step of the mechanism by which organophosphorous anticholinesterases of the general formula inhibit AChE is related to the acidity of X and to the bond strength of the P—X bond. For a series of compounds, aryl N-methyl methyl phosphoramidates, in which the P—X bond is constant, this paper shows that the quantum chemically calculated P-O total overlap populations (TOPs) correlate the experimental log I50 for inhibition of AChE over four orders of magnitude with correlation coefficients of 0.96 [r2: TOP 0.9581; (TOP)1/2 0.9614]. |
| Databáze: | OpenAIRE |
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