A structure-activity relationship study of organophosphorus compounds

Rohrbaugh, R. H.; Jurs, P. C.; Ashman, William P.; Davis, E. G.; Lewis, JW

doi:10.1021/tx00002a006

Cited by 10 publications

(4 citation statements)

References 18 publications

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“…Recently, it has been estimated that the number of representatives of Schedule 1.A.1 alone is 2,347,712, and the number of their derivatives assigned to Schedule 2.B.4 will be the same. The most toxic compounds from Schedule 1.A.1 contain branched alkyls with 4–6 carbon atoms in the ester groups . Derivatives containing long carbon chains in ester groups are indeed unlikely to be considered mass-produced CWA due to their price, availability, and relatively low toxicity .…”

Section: Introductionmentioning

confidence: 99%

“…The most toxic compounds from Schedule 1.A.1 contain branched alkyls with 4−6 carbon atoms in the ester groups. 25 Derivatives containing long carbon chains in ester groups are indeed unlikely to be considered massproduced CWA due to their price, availability, and relatively low toxicity. 18 However, their use for criminal purposes cannot be ruled out.…”

Section: Introductionmentioning

confidence: 99%

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Application of Chemical Ionization in the Analysis of Ethylphosphonic Acid Derivatives

Boczkowski,

Popiel,

Nawała

2024

J. Am. Soc. Mass Spectrom.

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The microsynthesis of 32 dialkyl derivatives of ethylphosphonic acid and the same number of monoalkyl derivatives was carried out to perform comparative studies using gas chromatography combined with mass spectrometry in chemical ionization mode which is one of the analytical techniques recommended by the Organisation for the Prohibition of Chemical Weapons (OPCW). The huge number of possible representatives makes it difficult to have complete spectral libraries of all substances in this class. Therefore, we decided to synthesize and instrumentally analyze only representatives of the selected series of homologues in this work. The analysis of the obtained results allowed us to find the rules for predicting mass spectra and the factors determining the retention parameters. Symmetrical diesters and monoesters of ethylphosphonic acid were selected for this study. During the conducted experiments using chemical ionization with methane as the reaction gas, protonated analyte molecules with high relative intensities were obtained; in many cases, these are base peaks in the spectrum. The obtained results allow grouping of the synthesized compounds depending on the introduced alkyl substituent. Retention data of the tested analytes were collected during the research by using electron ionization. The retention parameters of the tested compounds from each homologous series were also summarized and compared. Chemical Warfare Agents (CWA) analysis continues to be an important issue, especially in the context of the regular Proficiency Tests organized by the OPCW for identifying chemical compounds that are of interest to the Chemical Weapons Convention. Five compounds were synthesized whose spectra were not available in EI mass spectral libraries, and their retention indices were unknown. The identification of these substances was supported by the CI mass spectra and retention data, using previously developed relationships. Therefore, it is reasonable to conclude that the research method used is useful and effective.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Application of Chemical Ionization in the Analysis of Ethylphosphonic Acid Derivatives

Boczkowski,

Popiel,

Nawała

2024

J. Am. Soc. Mass Spectrom.

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“…Various studies have dealt with structure-activity relationships of OP nerve agents and pesticides, mainly focusing on the in vitro and in vivo toxicity of structural analogues [9][10][11][12][13][14][15][16][17][18]. Our group investigated the interaction of sarin and tabun analogues with human AChE and butyrylcholinesterase (BChE).…”

Section: Introductionmentioning

confidence: 99%

In Vitro Interaction of Organophosphono- and Organophosphorothioates with Human Acetylcholinesterase

et al. 2020

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The implementation of the Chemical Weapons Convention (CWC) in 1997 was a milestone in the prohibition of chemical warfare agents (CWA). Yet, the repeated use of CWA underlines the ongoing threat to the population. Organophosphorus (OP) nerve agents still represent the most toxic CWA subgroup. Defensive research on nerve agents is mainly focused on the “classical five”, namely tabun, sarin, soman, cyclosarin and VX, although Schedule 1 of the CWC covers an unforeseeable number of homologues. Likewise, an uncounted number of OP pesticides have been produced in previous decades. Our aim was to determine the in vitro inhibition kinetics of selected organophosphono- and organophosphorothioates with human AChE, as well as hydrolysis of the agents in human plasma and reactivation of inhibited AChE, in order to derive potential structure–activity relationships. The investigation of the interactions of selected OP compounds belonging to schedule 1 (V-agents) and schedule 2 (amiton) of the CWC with human AChE revealed distinct structural effects of the P-alkyl, P-O-alkyl and N,N-dialkyl residues on the inhibitory potency of the agents. Irrespective of structural modifications, all tested V-agents presented as highly potent AChE inhibitors. The high stability of the tested agents in human plasma will most likely result in long-lasting poisoning in vivo, having relevant consequences for the treatment regimen. In conclusion, the results of this study emphasize the need to investigate the biological effects of nerve agent analogues in order to assess the efficacy of available medical countermeasures.

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“…The enzyme regained attention recently, when the aging of the muscarinic ACh receptor in the brain was proven to be related to Alzheimer's disease (22). Structure-based descriptors have been found important in QSAR studies of AChE inhibition, suggesting an optimal shape/configuration that likely mimics the AChE receptor site (23).…”

Section: Introductionmentioning

confidence: 99%

Heterocyclic derivatives of 3-substituted-1,1,1-trifluoro-2-propanones as inhibitors of esterolytic enzymes

Székacs¹,

Halarnkar²,

Olmstead³

et al. 1990

Chem. Res. Toxicol.

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A structure-activity relationship study of organophosphorus compounds

Cited by 10 publications

References 18 publications

Application of Chemical Ionization in the Analysis of Ethylphosphonic Acid Derivatives

Application of Chemical Ionization in the Analysis of Ethylphosphonic Acid Derivatives

In Vitro Interaction of Organophosphono- and Organophosphorothioates with Human Acetylcholinesterase

Heterocyclic derivatives of 3-substituted-1,1,1-trifluoro-2-propanones as inhibitors of esterolytic enzymes

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