A5071643756- Pesticide Exposure and Toxicity
- Organophosphorus compounds synthesis
- Insect and Pesticide Research
- Fluorine in Organic Chemistry
- Cholinesterase and Neurodegenerative Diseases
- Pesticide and Herbicide Environmental Studies
- Synthesis and characterization of novel inorganic/organometallic compounds
- Environmental Toxicology and Ecotoxicology
- Synthesis and Reactions of Organic Compounds
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Nicotinic Acetylcholine Receptors Study
- Mass Spectrometry Techniques and Applications
- Bacillus and Francisella bacterial research
- Organic Chemistry Cycloaddition Reactions
- Chemical Reaction Mechanisms
- Organometallic Complex Synthesis and Catalysis
- Phosphorus compounds and reactions
- Synthesis and Biological Evaluation
- Chemical Synthesis and Analysis
- Inorganic Fluorides and Related Compounds
- Toxic Organic Pollutants Impact
- Synthesis of heterocyclic compounds
- Receptor Mechanisms and Signaling
- Advanced Chemical Physics Studies
- Carcinogens and Genotoxicity Assessment
Defence Science and Technology Laboratory
2015-2025
Salisbury University
1999-2018
Organisation for the Prohibition of Chemical Weapons
2018
University of York
2016
Google (United States)
2015
Goethe University Frankfurt
2008
Durham University
2005
Medical Research Council
2005
Proton (United Kingdom)
2005
On October 26, 2002, Russian Special Forces deployed a chemical aerosol against Chechen terrorists to rescue hostages in the Dubrovka theatre. Its use confirmed military interest chemicals with effects on personnel and caused 125 deaths through combination of inadequate medical care. This study provides evidence from liquid chromatography–tandem mass spectrometry analysis extracts clothing two British survivors, urine third survivor, that comprised mixture anaesthetics—carfentanil...
We describe the content and outcomes of First Workshop on Open-Ended Evolution: Recent Progress Future Milestones (OEE1), held during ECAL 2015 conference at University York, UK, in July 2015. briefly summarize workshop's talks, identify main themes that emerged from open discussions. Two important conclusions discussions are: (1) idea pluralism about OEE-it seems clear there is more than one interesting kind OEE; (2) importance distinguishing observable behavioral hallmarks systems...
The first organophosphorus nerve agent was discovered accidently during the development of pesticides, shortly after use chemical weapons (chlorine, phosgene) on battlefield World War I. Despite Chemical Weapons Convention banning these substances, they have still been employed in wars, terrorist attacks or political assassinations. Characterised by their high lethality, target nervous system inhibiting acetylcholinesterase (AChE) enzyme, preventing neurotransmission, which, if not treated...
The LD50 for soman is 10–20-fold higher a mouse than human. difference in susceptibility attributed to the presence of carboxylesterase but not human plasma. Our goal was make lacking plasma carboxylesterase. We used homologous recombination inactivate ES1 gene on chromosome 8 by deleting exon 5 and introducing frame shift amino acids translated from exons 6 13. ES1–/– mice have no detectable activity normal tissues. Homozygous wild-type littermates were tested response nerve agent model...
The standard treatment of atropine and oximes is insufficiently effective against all organophosphorus nerve agents. Bispyridinium non-oxime nicotinic antagonists are promising components to add treatments. One these, MB327, improves the survival guinea-pigs after intoxication with tabun, sarin or soman. We extend our previous study unsubstituted bispyridinium non-oximes C1 C10 alkane linkers analogues having 4- tert- butylpyridinium rings same linker range. report their effects on...
Enzymes that efficiently hydrolyze highly toxic organophosphorus nerve agents could potentially be used as medical countermeasures. As sufficiently active enzymes are currently unknown, we synthesized twelve fluorogenic analogues of with the 3-chloro-7-oxy-4-methylcoumarin leaving group probes for high-throughput enzyme screening. This set included pesticides paraoxon, parathion, and dimefox, DFP, tabun, sarin, cyclosarin, soman, VX, Russian-VX. Data from inhibition acetylcholinesterase, in...
A wide range of toxic organophosphorus pesticides and nerve agents is effectively hydrolyzed by the structurally related phosphotriesterase enzymes paraoxonase (PON1) from human plasma diisopropyl fluorophosphatase (DFPase) squid Loligo vulgaris. Both have potential use as medical countermeasures decontaminants. Enhanced enzymatic activity, stereochemical preference, substrate variety are still focus ongoing research. Derivatives bearing a fluorogenic leaving group were introduced for...
Standard treatment of poisoning by organophosphorus anticholinesterases uses atropine to reduce the muscarinic effects acetylcholine accumulation and oximes reactivate acetylcholinesterase (the effectiveness which depends on specific anticholinesterase), but does not directly address nicotinic poisoning. Bispyridinium molecules act as noncompetitive antagonists at receptors have been identified promising compounds one has shown improve survival following in guinea-pigs. Here, we investigated...
To support the effort to eliminate Syrian Arab Republic chemical weapons stockpile safely, there was a requirement provide scientific advice based on experimentally derived information both toxicity and medical countermeasures (MedCM) in event of exposure VM, VX or VM-VX mixtures. Complementary vitro vivo studies were undertaken inform that advice. The penetration rate neat VM not significantly different from VX, through either guinea pig skin vitro. presence did affect mixtures various...
Syntheses of 1,1-(propane-1,3-diyl)bis(4-tert-butylpyridinium) diiodide (MB327) and its di(methanesulfonate) salt (MB399) are described. Protection experiments in guinea-pigs showed that MB399, a noncompetitive nicotinic antagonist produces fast open channel block at the ion acetylcholine receptor, is able to improve survival animals poisoned with organophosphorus nerve agent soman when used therapeutically combination hyoscine physostigmine. Successful anti-nicotinic therapy, novel approach...
The Chemical Weapons Convention (CWC) aims to prohibit the development, production, acquisition, stockpiling, retention, transfer or use of chemical weapons by States Parties. Verification compliance investigations into allegations requires accurate detection warfare agents (CWAs) and their breakdown products. Detection CWAs such as organophosphorus nerve in environment relies mainly upon analysis soil. Here we present a novel method for agent VX its hydrolysis products through using...
The Chemical Weapons Convention prohibits the development, production, acquisition, stockpiling, retention, transfer or use of chemical weapons by Member States. Verification compliance and investigations into allegations require accurate detection warfare agents (CWAs) their degradation products. Detection CWAs such as organophosphorus nerve in environment relies mainly upon analysis soil. We now present a method for agent VX its hydrolysis products gas chromatography liquid mass...