Dichlofenthion
Introduction and History
Dichlofenthion is a fat-soluble organophosphorus compound primarily used in agricultural practices as a pesticide and nematicide to control a variety of insect pests. Organophosphates as a class were initially developed in the early 20th century, with some of the earliest compounds being synthesized as potential chemical warfare agents during and after World War I. However, their potent action on the nervous system quickly led to their adoption in agriculture to control pests that affect crops. Until the 21st century, they were among the most widely used insecticides available. Dichlofenthion emerged in the mid-20th century as part of the search for more effective and selective insecticides that could provide better crop protection with reduced environmental and health impacts.Structure Reactivity Synthesis
Source:Structure
The molecular structure of dichlofenthion includes a diethyl phosphorothioate group attached to a dichlorophenyl ring. This structure is crucial for its activity as an insecticide, with the phosphorothioate moiety playing a key role in the inhibition of acetylcholinesterase.Reactivity
Dichlofenthion is stable under normal conditions but can be hydrolyzed in the presence of strong acids or bases. It is also susceptible to oxidative degradation, which can lead to the formation of more toxic metabolites.Synthesis
The synthesis of dichlofenthion involves the reaction of 2,4-dichlophenol with diethyl thiophosphoryl chloride, which requires careful control of conditions to ensure the formation of the desired product and minimize by-products.Metabolism / Biotransformation
Biotransformation of dichlofenthion mainly occur during the formation of more polar conjugates as it is lipophilic. Therefore, causing for formation of metabolites during biotransformation which would result in change in toxicity. These biotransformation reactions involve Phase I and Phase II reactions.Phase I reaction
Phase I reaction involves oxidation and hydrolysis which would result in dichlofenthion reacting with polar groups such as hydroxyl, carboxyl, thiol and amino group. This would result in the formation of dichlorovinyl phosphate metabolite and other metabolites which may be more toxic than its parent compound.Hydrolysis of dichlofenthion occurs when plasma and tissue enzymes break down the phosphorus-ester bond present in dichlofenthion, leading to the formation of dichlorovinyl phosphate. These groups of enzymes are known as A-esterase or peroxidase, and by the cytochrome p-450 systems. A-esterase are located in plasma and hepatic endoplasmic reticulum and can hydrolyse organophosphorus compounds by splitting the anhydride, P-F, P-CN, or ester bond. Paraxonase is produced in the liver, together with cytochrome p0450 systems, both types of enzymes are also responsible for the hydrolysis of dichlofenthion. A study done by Environmental Health Perspectives to observe hydrolysis rate of organophosphates were measured and recorded in the table below. Although conditions were extreme, the study showed that there was presence of hydrolysis occurring for dichlofenthion.
| Chemical | Halflife, hr |
| Dichlofenthion | 19 |
Data of Ruzicks et al.
Oxidative reactions may also occur during Phase I metabolism of dichlofenthion. This involves an addition of oxygen to dichlofenthion, which can lead to the formation of oxidized intermediates which may be more polar than its parent compound. Oxidation reactions may also occur an oxidative cleavage of dichlofenthion, leading to the formation of metabolites with altered chemical properties. Thirdly, hydroxylation would lead to hydroxylated metabolites. Lastly, epoxidation, which involves the formation of episode function groups, would lead to the formation of reactive epoxide metabolites which can undergo further biotransformation to a more toxic compound.
Phase II reaction
Phase II reactions involve the conjugation of the parent compound or its Phase I metabolites with endogenous compounds to increase their water solubility and facilitate excretion. Common conjugation reactions include glucuronidation, sulfation, and amino acid conjugation. Dichlofenthion and its Phase I metabolites can undergo conjugation with molecules such as glucuronic acid, sulphate, or amino acids.Glucuronic acid molecules are added to dichlofenthion or its phase I molecules to its hydroxyl group, this process is known as glucuronidation, which is catalysed by enzymes UDP-glucuronosyltransferase. Sulfation refers to the addition of a sulphate group which is catalysed by sulfotransferase enzymes which utilizes 3’-phosphoadenosine-5'phosphosulfate. Sulphate group is usually added to hydroxyl or amino groups of the compound. Amino acid conjugation refers to the addition of an amino acid moiety like glycine or taurine to the compound on reactive functional groups. The reaction of catalysed in the liver and other.
However, it is notable that the biotransformation pathways of dichlofenthion can vary based on species, individual genetic makeup, and environmental factors due to the presence and absence of different enzymes. Hence, it is important to account for the type of organism when assessing risk and for the development of treatments in cases of poisoning. This can be done through research that monitors biotransformation of dichlofenthion in different organisms.
Use/Purpose, Availability, Efficacy
Dichlofenthion is an organophosphate insecticide that has been used in agricultural settings to control a variety of insect pests. The detailed uses, availability, and efficacy of dichlofenthion involve several aspects, including its application on crops, regulatory status, and effectiveness against pests.Detailed Uses
Dichlofenthion is used for agricultural pest control on fruits, vegetables, grains, and ornamental plants. It works well against aphids, caterpillars, beetles, leafhoppers, and mites. It is also used as livestock and poultry pest control, used in the facilities to control mosquitoes and flies. It is helpful against flies, ticks, lice, and other ectoparasites that can affect the health and productivity of livestock and poultry. This compound can also help with stored product protection such as grains, seeds, and other agricultural products. It keeps away weevils, beetles, and moths during transportation of the produce and storage.For the public, dichlofenthion is also used to help with vector control. It works toward mosquitoes and flies to prevent the spread of diseases like malaria, dengue fever, zika virus, and west Nile virus in the population. It can be applied to breeding sites, resting areas, or sprayed over large area. Besides that, this compound can be used to control residential pests like ants, cockroaches, and spiders. This can be seen in the presence of this compound in household pest sprays, baits, and granules.
Availability
The availability of dichlofenthion is heavily influenced by its regulatory status, which varies by country and region. Due to concerns over toxicity and environmental impact, its use has been restricted or banned in some jurisdictions. Regulatory agencies, such as the Environmental Protection Agency in the United States, Chemical safety and biosafety, or the European Food Safety Authority in the European Union, assess the safety and approve the use of pesticides like dichlofenthion.Where it is registered for use, dichlofenthion can be found in various formulations mentioned above, including emulsifiable concentrates and granules, designed to suit different application needs and crop types. The availability of these products is high as this chemical can be found in a variety of household and agricultural products.
Efficacy
Dichlofenthion is effective against a broad spectrum of insect pests. Its mode of action, inhibiting acetylcholinesterase, is generally effective against a wide range of insects. Dichlofenthion can achieve a high mortality rate towards pests as it inhibits acetylcholinesterase. AChE hydrolyses the neurotransmitter acetylcholine in insects to terminate neuronal excitement at the postsynaptic membrane. Therefore, it uses targeted towards pest control in different aspects of society is effective.However, the efficacy of dichlofenthion can be compromised by the development of resistance in pest populations through natural selection. Surviving pests may carry a gene that may help with the resistance towards dichlofenthion. This issue is not unique to dichlofenthion but is a common challenge with all insecticides. Therefore, integrated pest management practices, including the rotation of insecticides with different modes of action, are recommended to preserve the efficacy of products like dichlofenthion.
Molecular mechanism of action
Dichlofenthion is an acetylcholinesterase inhibitor. The detailed mechanism of action of dichlofenthion, an organophosphate insecticide, involves the inhibition of the enzyme acetylcholinesterase, which plays a critical role in nerve signal transmission. Acetylcholinesterase is responsible for breaking down acetylcholine, a neurotransmitter, in the synaptic cleft, which is the gap between neurons or between a neuron and a muscle cell. By degrading acetylcholine, AChE terminates the signal transmission, allowing the nerve cells to reset for the next signal. When dichlofenthion inhibits AChE, it causes an accumulation of acetylcholine in the synaptic cleft. This leads to continuous stimulation of the nerves, muscles, and glands, resulting in a range of symptoms and potential for toxicity.Breakdown of Molecular Mechanism of Action of Dichlofenthion
;Acetylcholine and AcetylcholinesteraseAcetylcholine is a neurotransmitter involved in the transmission of nerve impulses across synapses and neuromuscular junctions. It binds to receptors on the post-synaptic neuron or muscle cell, initiating a response.
Acetylcholinesterase is the enzyme responsible for breaking down ACh in the synaptic cleft, the space between neurons or between a neuron and a muscle cell. This breakdown is necessary to terminate the signal and allow the synapse to reset for the next transmission.
;Interaction of Dichlofenthion with AChE
- Inhibition of AChE: Dichlofenthion, being an organophosphate compound, irreversibly binds to the serine hydroxyl group in the active site of acetylcholinesterase. This action forms a covalent bond between the enzyme and dichlofenthion, which irreversibly deactivates AChE as an enzyme, rendering AChE unable to hydrolyze acetylcholine.
- Accumulation of ACh: As a result of AChE inhibition, ACh accumulates in the synaptic cleft because it cannot be properly metabolized. This leads to continuous stimulation of the receptors on the post-synaptic neuron or muscle cell.
- Overstimulation: The overaccumulation of ACh results in continuous stimulation of both muscarinic and nicotinic acetylcholine receptors which becomes excessive. Muscarinic receptors are found in various tissues throughout the body, including smooth muscle, cardiac muscle, and glands. When overstimulated, muscarinic receptors cause symptoms such as salivation, lacrimation, urination, defecation, gastric cramps, emesis, and miosis. Nicotinic receptors are primarily located in the neuromuscular junctions of skeletal muscle fibres. Nicotinic receptor overstimulation leads to sweating, muscle twitching, weakness, paralysis, and potentially respiratory failure due to paralysis of the diaphragm. The overstimulation of these receptors leads to excessive cholinergic activity in the nervous system and other target tissues.