Paraquat dichloride (T3D0808)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (4)XML
Targets (4)
Record Information
Version2.0
Creation Date2009-06-03 21:56:02 UTC
Update Date2014-12-24 20:22:51 UTC
Accession NumberT3D0808
Identification
Common NameParaquat dichloride
ClassSmall Molecule
DescriptionParaquat dichloride is a constituent of numerous proprietary herbicides. A large majority (93%) of fatalities from paraquat poisoning are cases of intentional self-administration, ie, suicides. In third world countries, paraquat is a major suicide agent. For instance, in Samoa from 1979-2001, 70% of suicides were by Paraquat poisoning. In Southern Trinidad from 1996-1997, 76% of suicides were by paraquat. However, independent bodies have studied paraquat in this use. Jenny Pronczuk de Garbino, stated: no lung or other injury in marijuana users has ever been attributed to paraquat contamination. Also a United States Environmental Protection Agency manual states: … toxic effects caused by this mechanism have been either very rare or nonexistent. Most paraquat that contaminates marijuana is pyrolyzed during smoking to dipyridyl, which is a product of combustion of the leaf material itself (including marijuana) and presents little toxic hazard. Paraquat is the trade name for N,N -dimethyl-4,4 -bipyridinium dichloride, one of the most widely used herbicides in the world. Paraquat, a viologen, is quick-acting and non-selective, killing green plant tissue on contact. It is also toxic to human beings when swallowed. Paraquat is used as a quaternary ammonium herbicide; one of the most widely used herbicides in the world. It is quick-acting, non-selective, and kills green plant tissue on contact. It is redistributed within the plant but does not harm mature bark. Being a herbicide, paraquat protects crops by controlling a wide range of annual and certain perennial weeds that reduce crop yield and quality by competing with the crop for water, nutrients, and light. Pure paraquat ingested is highly toxic to mammals and humans potentially leading to acute respiratory distress syndrome (ARDS), and there are no specific antidotes. However, fuller's earth or activated charcoal is an effective treatment, if taken in time. Death may occur up to 30 days after ingestion. Diluted paraquat used for spraying is less so, thus the greatest risk of accidental poisoning is during mixing and loading Paraquat for use.
Compound Type
  • Aromatic Hydrocarbon
  • Food Toxin
  • Herbicide
  • Lachrymator
  • Metabolite
  • Organic Compound
  • Pesticide
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
1, 1'-Dimethyl-4,4'-bipyridynium dichloride
1,1 -Dimethyl-4,4 -bipyridinium
1,1'-Dimethyl-4, 4'-dipyridylium chloride
1,1'-Dimethyl-4,4'-bipyridinium dichloride hydrate
1,1'-Dimethyl-4,4'-bipyridynium dichloride
1,1'-Dimethyl-4,4'-dipyridinium-dichlorid
1,1'-Dimethyl-4,4'-dipyridylium dichloride
1,1'-Dimethyl-[4,4'-bipyridin]-1,1'-diium dichloride
1,1-Dimethyl-4,4-dipyridilium dichloride
4,4'-Bipyridinium, 1,1'-dimethyl-, dichloride
4,4'-Dimethyldipyridyl dichloride
Bipyridinium, 1,1'-dimethyl-4,4'-, dichloride
Cekuquat
Crisquat
Dextrone X
Dextrone-x
Dexuron
Dimethyl viologen chloride
Dimethyldipyridyl chloride
Dwuchlorek 1,1'-dwumetylo-4,4'-dwupirydyniowy
Esgram
Galokson
Goldquat 276
Gramixel
Gramoxone
Gramoxone D
Gramoxone dichloride
Gramoxone S
Gramoxone w
Gramuron
Herbaxon
Herboxone
Methyl viologen
Methyl viologen (reduced)
Methyl viologen dichloride
Methyl-Viologen
Methylviologen chloride
N,N'-Dimethyl-4, 4'-dipyridylium dichloride
N,N'-Dimethyl-4,4'-bipyridinium dichloride
N,N'-Dimethyl-4,4'-bipyridylium dichloride
N,N'-Dimethyl-4,4'-dipyridylium dichloride
N,N'-Dimethylviologen
Ortho paraquat CL
Parakwat
Paraquat chloride
Paraquat CL
Paraquat, dichloride
Paraquat-dichloride
Pathclear
Pillarquat
Pillarxone
Toxer total
Chemical FormulaC12H14Cl2N2
Average Molecular Mass257.159 g/mol
Monoisotopic Mass256.053 g/mol
CAS Registry Number1910-42-5
IUPAC Name1,1'-dimethyl-[4,4'-bipyridine]-1,1'-diium
Traditional Namestarfire
SMILES[Cl-].[Cl-].C[N+]1=CC=C(C=C1)C1=CC=[N+](C)C=C1
InChI IdentifierInChI=1S/C12H14N2.2ClH/c1-13-7-3-11(4-8-13)12-5-9-14(2)10-6-12;;/h3-10H,1-2H3;2*1H/q+2;;/p-2
InChI KeyInChIKey=FIKAKWIAUPDISJ-UHFFFAOYSA-L
Chemical Taxonomy
Description belongs to the class of organic compounds known as bipyridines and oligopyridines. These are organic compounds containing two pyridine rings linked to each other.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassBipyridines and oligopyridines
Direct ParentBipyridines and oligopyridines
Alternative Parents
Substituents
  • Bipyridine
  • 4,4p-bipyridinium
  • N-methylpyridinium
  • Pyridinium
  • Heteroaromatic compound
  • Azacycle
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organic cation
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceOff-white powder (12).
Experimental Properties
PropertyValue
Melting Point>400°C
Boiling PointNot Available
Solubility700 mg/mL at 20°C
LogP-4.5
Predicted Properties
PropertyValueSource
Water Solubility0.00016 g/LALOGPS
logP-4.2ALOGPS
logP-6.7ChemAxon
logS-6.2ALOGPS
Physiological Charge2ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area7.76 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity59.19 m³·mol⁻¹ChemAxon
Polarizability22 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0900000000-8e105da1b5a413b7cded2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-0900000000-ef5d5e61533df6c42e3e2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00yr-3900000000-42168478ffe7524d86622016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0900000000-26e90595decaaf33fd6f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-0900000000-85b4cce5855b8138989f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00n0-1900000000-db10deb753c3a3973cc92016-08-03View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, experimental)Not Available2018-06-06View Spectrum
1D NMR13C NMR Spectrum (1D, 50.18 MHz, D2O, experimental)Not Available2018-06-06View Spectrum
Toxicity Profile
Route of ExposureInhalation (7) ; oral (7) ; eye contat (7) ; dermal (7)
Mechanism of ToxicityThe mechanisms of the toxic effects of paraquat are largely the result of a metabolically catalyzed single electron oxidation reduction reaction, resulting in depletion of cellular NADPH and the generation of potentially toxic forms of oxygen such as the superoxide radical (2). Recent studies have demonstrated paraquat cytotoxicity occurs in the mitochondria and particularly in mitochondrial-rich tissues. The mitochondrial NADH-dependent PQ reductase containing a voltage-dependent anion channel 1 (VDAC1) appears to be largely responsible for paraquat cytotoxicity. When mitochondria are incubated with NADH and paraquat, the superoxide anion is produced, and the mitochondria rupture. Ruptured mitochondria lead to rapid cell death (1).
MetabolismParaquat is poorly absorbed after oral exposure. It is not metabolized but is reduced to an unstable free radical which is then re-oxidized to reform the cation and produce a superoxide anion. It is excreted moslty in the urine,and in small fraction also in the feces (3, 13).
Toxicity ValuesLD50: 150 mg/kg (Oral, Rat) (13) LD50: >480 mg/kg (Dermal, Rabbit) (13)
Lethal Dose35 mg/kg
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesParaquat is used as a quaternary ammonium herbicide; one of the most widely used herbicides in the world. It is also often used in science to catalyze the formation of reactive oxygen species (ROS). (12).
Minimum Risk LevelNot Available
Health EffectsIt can cause temporary damage to nails and if swalloed, may cause nose bleeding. Long term exposures to paraquat would most likely cause lung and eye damage. Some suspect a possible link to a greater incidence of Parkinson's disease. Pancreatitis may develop in some cases of acute. Paraquat is caustic to the oral, esophageal, and gastric mucosa (6, 4, 12).
SymptomsEye or skin irritation; hypotension may develop after large ingestion; epistaxis and sore throat may develop after inhalation. Nausea, vomiting, diarrhea, and abdominal pain are common (6).
TreatmentIn case of oral exposure, administer charcoal as a slurry. Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion. The treatment is symptomatic and supportive. In case of eye exposure, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. In case of dermal exposure, remove contaminated clothing and jewellery. Wash the skin, including hair and nails, vigorously; do repeated soap washings. Discard contaminated clothing. (6)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB33121
PubChem Compound ID15938
ChEMBL IDCHEMBL458019
ChemSpider ID15146
KEGG IDC00225
UniProt IDNot Available
OMIM ID
ChEBI ID28786
BioCyc IDNot Available
CTD IDNot Available
Stitch IDParaquat
PDB IDNot Available
ACToR ID6503
Wikipedia LinkParaquat_dichloride
References
Synthesis Referencehttp://informahealthcare.com/doi/pdf/10.3109/15563657909030112
MSDST3D0808.pdf
General References
  1. Shimada H, Hirai K, Simamura E, Hatta T, Iwakiri H, Mizuki K, Hatta T, Sawasaki T, Matsunaga S, Endo Y, Shimizu S: Paraquat toxicity induced by voltage-dependent anion channel 1 acts as an NADH-dependent oxidoreductase. J Biol Chem. 2009 Oct 16;284(42):28642-9. doi: 10.1074/jbc.M109.033431. Epub 2009 Aug 28. [19717555 ]
  2. Griffin JB, Stanley JS, Zempleni J: Synthesis of a rabbit polyclonal antibody to the human sodium-dependent multivitamin transporter. Int J Vitam Nutr Res. 2002 Jul;72(4):195-8. [12214555 ]
  3. Dey S, Subramanian VS, Chatterjee NS, Rubin SA, Said HM: Characterization of the 5' regulatory region of the human sodium-dependent multivitamin transporter, hSMVT. Biochim Biophys Acta. 2002 Mar 19;1574(2):187-92. [11955628 ]
  4. Liden M, Eriksson U: Development of a versatile reporter assay for studies of retinol uptake and metabolism in vivo. Exp Cell Res. 2005 Nov 1;310(2):401-8. Epub 2005 Sep 8. [16150442 ]
  5. Bairaktari E, Katopodis K, Siamopoulos KC, Tsolas O: Paraquat-induced renal injury studied by 1H nuclear magnetic resonance spectroscopy of urine. Clin Chem. 1998 Jun;44(6 Pt 1):1256-61. [9625050 ]
  6. Rumack BH (2009). POISINDEX(R) Information System. Englewood, CO: Micromedex, Inc. CCIS Volume 141, edition expires Aug, 2009.
  7. Mackison FW, Stricoff RS, and Partridge LJ Jr. (eds) (1981). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office.
  8. Worthing, CR and SB Walker (1987). The Pesticide Manual - A World Compendium. 8th ed. Thornton Heath, UK: The British Crop Protection Council.
  9. The Chemical Society (1970). Foreign Compound Metabolism in Mammals. Volume 1: A Review of the Literature Published Between 1960 and 1969. London: The Chemical Society.
  10. WHO (1984). Environmental Health Criteria: Paraquat and Diquat.
  11. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
  12. Wikipedia. Paraquat. Last Updated 8 August 2009. [Link]
  13. IPCS Intox Database (1987). Paraquat. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Transient receptor potential cation channel subfamily A member 1
General Function:
Temperature-gated cation channel activity
Specific Function:
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
Gene Name:
TRPA1
Uniprot ID:
O75762
Molecular Weight:
127499.88 Da
References
  1. Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]
Target Details
2. Voltage-dependent anion-selective channel protein 1
General Function:
Voltage-gated anion channel activity
Specific Function:
Forms a channel through the mitochondrial outer membrane and also the plasma membrane. The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis. It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The open state has a weak anion selectivity whereas the closed state is cation-selective (PubMed:11845315, PubMed:18755977, PubMed:20230784, PubMed:8420959). May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis (PubMed:15033708, PubMed:25296756).
Gene Name:
VDAC1
Uniprot ID:
P21796
Molecular Weight:
30772.39 Da
References
  1. Shimada H, Hirai K, Simamura E, Hatta T, Iwakiri H, Mizuki K, Hatta T, Sawasaki T, Matsunaga S, Endo Y, Shimizu S: Paraquat toxicity induced by voltage-dependent anion channel 1 acts as an NADH-dependent oxidoreductase. J Biol Chem. 2009 Oct 16;284(42):28642-9. doi: 10.1074/jbc.M109.033431. Epub 2009 Aug 28. [19717555 ]
Target Details
3. Multidrug and toxin extrusion protein 1
General Function:
Monovalent cation:proton antiporter activity
Specific Function:
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.
Gene Name:
SLC47A1
Uniprot ID:
Q96FL8
Molecular Weight:
61921.585 Da
Target Details
4. Solute carrier family 22 member 2
General Function:
Quaternary ammonium group transmembrane transporter activity
Specific Function:
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.
Gene Name:
SLC22A2
Uniprot ID:
O15244
Molecular Weight:
62579.99 Da