4685-14-7

Usage

Uses

Used in Agriculture:
Paraquat is used as a herbicide for controlling a wide range of weeds, benefiting more than a hundred crops such as cereals, oil seeds, fruits, and vegetables, which grow in all climates.
Used in Plant Protection Products:
Paraquat is used as a chemical weed killer in plant protection products, offering outstanding properties that set it apart from other agents used in this industry.
Used in Occupational Health:
Paraquat can cause contact and phototoxic contact dermatitis, acne, and leucoderma, primarily affecting agricultural workers.

References

https://en.wikipedia.org/wiki/Paraquat https://pubchem.ncbi.nlm.nih.gov/compound/15939#section=Reactive-Group http://www.toxipedia.org/display/toxipedia/Paraquat http://paraquat.com/knowledge-bank/paraquat-fact-sheet

Production Methods

Paraquat is produced in several countries by coupling pyridine in the presence of sodium in anhydrous ammonia and quaternizing the resulting 4,4-bipyridyl with methyl chloride. The only impurity permitted is the 4,40-bipyridyl at a maximum level of 0.25% of the paraquat content. It is formulated for commercial use in various concentrations and mixtures. In the United States, paraquat is sold in watersoluble concentrates at 1.5–2.5 lb/gal.

Preparation

Paraquat is synthesized by the direct quaternization of 4,4 -bipyridyl with chloromethane under pressure (1,9). Diquat is synthesized by reaction of 2,2 -bipridyl with di-n-propyl amine.

Health Hazard

Paraquat salts show moderate to high acutetoxicity among species, the oral LD50 values ranging between 25 and 300 mg/kg.The LD50 values in dogs, cats, guinea pigs,and rats are 25, 35, 30, and 100 mg/kg,respectively, for the sulfate salts. The toxicsymptoms from ingestion and inhalationof dusts include headache, nausea, vomiting, diarrhea, ulceration, dyspnea, and lunginjury. Single exposure to paraquat aerosols 3–5 mm in diameter at 1 mg/m3 concentration for 6 hours caused death to rats (ACGIH 1986). Inhalation of nonrespirable size dustscaused intense irritation and nose bleeding.Repeated exposures can lead to severe pulmonary edema and fibrosis. The dusts are anirritant to the respiratory tract.Dey and associates (1990) investigatedparaquat pharmacokinetics in rats, using asubcutaneous toxic low dose (72 mmol/kg)of [14CH3] paraquat, which would producelung disease but no renal damage. Paraquatwas rapidly absorbed. Peak blood concentrations were 58 nmol/mL at 20 minutes,while its peak concentrations in the lungand kidney were 65 and 359 nmol/g, respectively, at 40 minutes. About 85% of dosewas eliminated in the urine by 7 days. Of theremaining radioactivity, 79% remained in thebody and 21% remained in the lung, causing progressive lung disease. Excretion ofthe retained amount was slow and prolonged.Chui and coworkers (1988) investigated thetoxicokinetics of paraquat and the effects ofdifferent routes of administration. A singledose of 11.4 mg/kg of [14CH3 ]paraquat wasadministered in rats by intravenous, intragastric, dermal, and pulmonary (exposure byaqueous or liquid aerosols) routes. The majorexcretion routes were urine and feces.The radioactivity absorbed into thesystemic circulation of the rat was about27.5, 23.8, 8.5, and 1.5 nmol for inhalationthrough a tracheal cannula, nose-only expo-sure, intragastric injection, and dermalabsorption, respectively. The bulk of theherbicide administered by the inhalation anddermal routes remained at the sites of theadministration.In humans, cardiovascular collapse result-ing from acute paraquat poisoning is asso-ciated with the distribution phase; the lateoccurrence of death-related pulmonary fibro-sis is associated with the elimination phase(Houze et al. 1990). Toxicokinetics studiesconducted by these investigators in acutehuman poisoning cases indicated a concen-tration of paraquat in blood that had a mean distribution half-life of 5 hours and a meaneliminationhalf-lifeof84 hours,respectively.It was excreted in the urine. It was retainedin the muscle for several weeks after poi-soning. Electron microscopy studies (TEMand SEM) on the lungs obtained from adog after 7 days of intravenous administra-tion of paraquat (12 mg/kg) indicate detach-ment of alveolar epithelial cells and alve-olar macrophage, which plays a significantrole in paraquat-induced pulmonary fibrosis(Hampson and Pond 1988). Administrationof paraquat to adult rat pulmonary alveolarmacrophages in primary culture caused celldeaththatwasdependentonthedoseandtime.The cell death was potentiated by hyperoxia(95% O) and extracellular production of anactive oxygen species, the superoxide anionradical (Wong and Stevens 1985). Althoughdiquat can enter the cells to a greater extent,than can paraquat, the latter is about twice aspotent as diquat (Wong and Stevens 1986).Paraquat is a urinary metabolite of 4,48-bipyridyl when the latter is administeredintraperitoneally to guinea pigs. Godin andCrooks (1989) detected 2.9% N-methyl-4,48-bipyridinium ion in the urine of animalstreated with 4,48-bipyridyl, thus indicat-ing the formation of such toxic metabolitesthrough the N-methylation pathway.Certain substances have been reported topotentiate the toxicity of paraquat. Theseinclude transition metal ions such as copper(Kohen and Chevion 1985) and ethanol (Kuoand Nanikawa 1990). Blood paraquat lev-els showed significant elevation in rabbits,and the mortality rates increased when theanimals were orally administered paraquatcombined with ethanol in amounts of 2.0and 3.8 g/kg. Continuous breathing of highoxygen concentrations 12–24 hours afteradministration of paraquat caused severe andextensive pulmonary lesions and interstitialfibrosis (Selman et al. 1985). On the otherhand, a reverse sequence of treatment—inhalation of high oxygen concentrations followed by paraquat administration—causedno mortality and pulmonary lesions.The effect of light on toxicity of paraquathas been reported (Barabas et al. 1986). A72-hour exposure to illumination increasedthe lethality of paraquat in mice. Changesin the activity of the enzymes, catalase, superoxide dismutase, and glutathione peroxidase,were also noted after exposure to light.Antidote actions of a few substancesagainst paraquat toxicity have been reported.These include several sodium sugar sulfates,including dextran sulfate, cellulose sulfate,chondroitin sulfate, sucrose sulfate, and glu-cose sulfate (Tsuchiya et al. 1989; Ukai et al.1987). Sugar sulfates 2000 mg/kg, givenorally immediately after paraquat ingestion (200 mg/kg), protected mice againstthe acute toxicity of the herbicide. Thiols,cystein, d-penicillamine, and GSH were found to protect mice against a LD50 dose of paraquat(Szabo et al. 1986). The protecting actionof these compounds decreased in the ordernoted above.

Trade name

HERBICIDE?[C]; CRISQUAT?; CYCLONE?; DEXTRONE?; DEXTRONE-X?; ESGRAM?; GAMIXEL?; GOLDQUAT 276?; GRAMOXONE?; GRAMOXONE D?; GRAMOXONE DICHLORIDE?; GRAMOXONE S?; GRAMOXONE W?; HERBIKILL?; HERBOXONE?; OK 622?; ORTHO PARAQUAT CL?[C]; PARA-COL?; PARAMINE?; PARAQUAT CL?[C]; PARAQUAT DICHLORIDE BIPYRIDYLNIUM HERBICIDE?; PATHCLEAR?; PILLARQUAT?; PILLARXONE?; PP148?; PRELUDE?[C]; STARFIRE?; SUREFIRE?; SWEEP?; TERRAKLENE?; TOTACOL?; TOXER TOTAL?; UNIQUAT?; WEEDOL?

Safety Profile

Poison by ingestion and intraperitoneal routes. Mutation data reported. Human systemic effects: changes in structure or function of esophagus, darrhea, edema, fibrosis of lung, fibrosis, focal (pneumoconiosis), hemorrhage, jaundice, renal damage, renal function tests depressed, respiratory depression, ulceration or bleedmg from stomach, vomiting. Death from anoxia may result. When heated to decomposition it emits toxic fumes of NOx. See also PARAQUAT DICHLOFUDE

Carcinogenicity

Several carcinogenicity studies have been conducted on paraquat by the oral route. In a 2-year feeding study at doses as high as 75 mg/kg in mice, and a drinking water study at doses as high as 2.6 mg/L of water in rats, no evidence of tumorigenicity was seen. Similar negative results were reported for diquat in a 2-year feeding study (Hayes, 1991) in rats at dose levels up to 720 mg/kg and in a 2-year drinking water study in mice at doses of 2–4 mg/kg.

Metabolism

Because paraquat and diquat are positively charged ions, they are very quickly and tightly bound to negatively charged clay particles in the soil, rendering them totally inactive (1). Thus, these herbicides have no soil activity. Plants do not actively metabolize either paraquat or diquat (31); however, substantial photodegradation does occur on the leaf surface. Isonicotinic acid and methylamine hydrochloride are the decomposition products most often noted from paraquat (1). With diquat, the decomposition products included the pyrazinium salt, picolinamide, and picolinic acid (1). Photodegradation of diquat was greater than that of paraquat at equal irradiances (1–3).

Toxicity evaluation

Paraquat is most active in rapidly respiring tissue and in the presence of oxygen, it is not surprising that most of the damage in mammalian systems is associated with lung tissue. Symptoms such as fibrosis and hemorrhage of the lungs are often detected after paraquat poisoning.

InChI:InChI=1/C12H14N2/c1-13-7-3-11(4-8-13)12-5-9-14(2)10-6-12/h3-10H,1-2H3/q+2

Synthetic route

Paraquat (4685-14-7, 25128-26-1) → paraquat radical (4685-14-7)

Conditions	Yield
With ethylenediaminetetraacetic acid; dihydroxytin(IV) uroporphyrin I Quantum yield; Irradiation; triethanoilamine as electron donor; photoreduction of methylviologen sensitized by dihydroxytin(IV) uroporphyrin, pH dependence;

Upstream product

• 553-26-4 4,4'-bipyridine 
• 74-83-9 methyl bromide 
• 11121-48-5 2,4,5,7-tetraiodo-3',4',5',6'-tetrachlorofluorescein dianion 
• 26985-31-9 methyl viologen cation radical 
• 143984-03-6 5,5-dimethyl-4-ethyl-2-oxomorpholin-3-yl 
• 137668-70-3 5,5-dimethyl-4-ethyl-3-methoxy-2-oxomorpholine 
• 299-36-5 ascorbate 
• 15591-62-5 methyl viologen radical cation 
• 83214-30-6 C₁₂H₁₄N₂⁽²⁺⁾*C₁₀H₁₂O 
• 714905-09-6 1,1'-Dimethyl-1',4'-dihydro-[4,4']bipyridinyl-1-ium 
• 99666-80-5 [ruthenium(III)-bis(2,2'-bipyridine)-(4,4'-dimethyl-2,2'-bipyridine)]⁽³⁺⁾ 
• 1983-60-4 methyl vilogen diiodide 
• 4685-14-7 Paraquat 
• 1910-42-5 paraquat dichloride 

Downstream Products

• 26985-31-9 methyl viologen cation radical 
• 50-00-0 formaldehyd 
• 124-38-9 carbon dioxide 
• 688-57-3 ethylenediamine-N,N,N'-triacetic acid 
• 1081-34-1 2,2':5',2''-terthiophene radical cation 
• 5930-71-2 bis(dimethyloxyphosphinothioyl) disulfide 
• 11121-48-5 2,4,5,7-tetraiodo-3',4',5',6'-tetrachlorofluorescein dianion 
• 505-73-7 disulfanediyldiacetic acid 
• 4685-14-7 1,1'-dimethyl-4,4'-dipyridylium radical cation 
• 83214-30-6 C₁₂H₁₄N₂⁽²⁺⁾*C₁₀H₁₂O 
• 18983-82-9 CO⁽¹⁸⁾O 
• 4685-14-7 Paraquat 
• 652-29-9 2',3',4',5',6'-pentafluoroacetophenone 
• 653-37-2 perfluorobenzaldehyde 

Relevant academic research and scientific papers

Tuning radical interactions in trisradical tricationic complexes by varying host-cavity sizes

Although host-guest pairing interactions between bisradical dicationic cyclobis(paraquat-p-phenylene) (BB2(+)) and the bipyridinium radical cation (BIPY+) have been studied extensively, host molecules other than BB2(+) are few and far between. Herein, four bisradical dicationic cyclophanes with tunable cavity sizes are investigated as new bisradical dicationic hosts for accommodating the methyl viologen radical cation (MV+) to form trisradical tricationic complexes. The structure-property relationships between cavity sizes and binding affinities have been established by comprehensive solution and solid-state characterizations as well as DFT calculations. The association constants of the four new trisradical tricationic complexes are found to range between 7400 and 170?000 M-1, with the strongest one being 4.3 times higher than that for [MV?BB]3(+). The facile accessibility and tunable stability of these new trisradical tricationic complexes make them attractive redox-controlled recognition motifs for further use in supramolecular chemistry and mechanostereochemistry.

DEEP EUTECTIC SOLVENT COMPOSITIONS

Disclosed herein are compositions of a deep eutectic solvent with a host, such as a supramolecular host, and the use of the composition to form a composition comprising the host in complex with one or more guests. The deep eutectic solvent provides an alternative medium to the aqueous-based media that have been used in the art to date. Also disclosed are compositions of a deep eutectic solvent with a redox-active compound, such as a viologen compound, and the use of the composition, for example, in a smart window or for agricultural use, such as in an agricultural product.

DESolution of CD and CB Macrocycles

Supramolecular chemistry utilizing the macrocyclic hosts cyclodextrins (CDs) and cucurbit[n]urils (CB[n]s) is traditionally performed in aqueous media; however, their solubility is typically poor, especially for the family of CB[n]s. Through derivatization of these macrocycles their solubility can be augmented to enable enhanced solubility in water and in some organic solvents. The increase in solubility of these derivatized macrocycles allows for their use in a wider range of chemical environments and giving rise to myriad potential applications. The dissolution of parent CDs (α-, β- and γ-) and CB[n]s (n=6–8) in deep eutectic solvents (DES) is reported, showing dramatic enhanced solubility of the larger species in both families, CB[7] and CB[8] as well as β- and γ-CD, respectively. Furthermore, the host–guest properties are maintained in this new solvation medium.

Electrochemical oxidation of paraquat in neutral medium

Abstract Steel, Pt and pelleted Co2FeO4 electrodes were used for the electrochemical oxidation of paraquat in aqueous solutions at room temperature. The oxide electrodes were characterized by cyclic voltammetry. Paraquat electrochemical oxidation was carried out by electrolysis at constant current and monitored by UV-vis absorbance measurements. Different anode/cathode pairs were used. After 1.5 h of electrolysis the highest removal (≈79%), was obtained with the electrode pair Pt/steel followed by Co2FeO4/Pt (≈55%), corresponding to the paraquat oxidation by a conversion mechanism. Removals of ≈64% were obtained with Co2FeO4 / Co2FeO4 after 3 h of electrolysis. Mass spectrometry analysis indicates that the main intermediate oxidation products were monopyridone and dipyridone derivatives.

Conversion of solar energy to chemical energy

The rate of evolution of hydrogen from water by photochemical process using solar energy has been investigated employing fourteen metal complexes as catalysts, ten electron relays, three electron donors and two co-catalysts in different permutation and combinations. The effect of varying reaction conditions like temperature, concentration and pH have also been investigated for the optimum production of hydrogen by the photochemical cleavage of water molecules.

Kinetics of paraquat and copper reactions with nitroxides: The effects of nitroxides on the aerobic and anoxic toxicity of paraquat

The toxicity of paraquat (PQ2+) is attributed to intracellularly formed PQ.+, O2.-, H2O2, and secondary ·OH radicals generated through Fenton-like reactions. Yet, no antidote for PQ2+ toxicity in human has been found also due to poor cell permeability of many common antioxidants that remove toxic species predominantly extracellularly. Cell-permeable nitroxides, which scavenge xenobiotic-derived deleterious radicals and detoxify redox-active metal ions, would be expected to ameliorate PQ2+ toxicity. We have studied using pulse radiolysis the kinetics of the reactions of 2,2,6,6-tetramethyl-piperidinoxyl (TPO) and 4-OH-TPO with PQ.+ and CuIIL2 (L = 1,10-phenanthroline, 2,2′-bipyridyl) in the absence and presence of DNA. We found that the rate constant for the reaction of PQ.+ with the nitroxides is about 4 orders of magnitude lower than that with O2. In addition, the rate of the reaction of the nitroxides with CuIL2 decreases as [DNA] increases, which suggests that nitroxides react significantly slower with bound metal ions. These results explain the failure of 4-OH-TPO to protect bacterial and mammalian cells from PQ2+ toxicity under air. In contrast, the rate of the reaction of PQ.+ with CuIIL2 was unaffected by DNA. Furthermore, copper toxicity has been attributed mainly to CuI and was observed predominantly for cells subjected to anoxic conditions. It implied that nitroxides would be effective protectants if PQ2+ induces toxicity also under anoxia. Surprisingly, we found that PQ2+ toxicity under anoxia was even greater than that under air, and under these conditions 4-OH-TPO protected the cells from PQ. These results indicate that the mechanism underlying the anoxic toxicity of PQ2+ differs from that operating in the presence of oxygen, and that reduced transition metal ions are most probably the species responsible for PQ2+ anoxic toxicity.

Mechanistic implications of a linear free-energy correlation of rate constants for the reduction of active- and Met-R2 forms of E. coli ribonucleotide reductase with eight organic radicals

Cross-reaction rate constants k12 (22 °C) at pH 7.0 have been determined for the reduction of Fe(III)2 and tyrosyl-radical-containing active-R2 from E. coli ribonucleotide reductase with eight organic radicals (OR), e.g., MV·+ from methyl viologen. The more reactive OR's were generated in situ using pulse radiolysis (PR) techniques, and other OR's were generated by prior reduction of the parent with dithionite, followed by stopped-flow (SF) studies. In both procedures it was necessary to include consideration of doubly-reduced parent forms. Values of k12 are in the range 109 to 104 M-1 s-1 and reduction potentials E1/(o) for the OR vary from -0.446 to +0.l94 V. Samples of E. coli active-R2 also have an Fe2(III) met-R2 component (with no Tyr·), which in the present work was close to 40%. From separate experiments met-R2 gave similar k12 rate constants (on average 66% bigger) to those for active-R2, suggesting that reduction of the Fe2/(III) center is the common rate-limiting step. A single Marcus free-energy plot of log k12 - 0.5 log f vs - E1/(o)/0.059 describes all the data, and the slope of 0.54 is in satisfactory agreement with the theoretical value of 0.50. It is concluded that the ratelimiting step involves electron transfer. In addition, the intercept at -E1/(o)/0.059 = 0 is 5.94, where values of the reduction potential and self-exchange rate constant for met-R2 contribute to this value. To maintain electroneutrality at the ~10 A buried active site H+ uptake is also required. For both e- and H+ transfer the conserved pathway Trp-48, Asp-237, His-118 to Fe(A) is a possible candidate requiring further examination.

Intramolecular Electron Transfer from Mn or Ligand Phenolate to Photochemically Generated RuIII in Multinuclear Ru/Mn Complexes. Laser Flash Photolysis and EPR Studies on Photosystem II Models

In a mononuclear MnIV and a trinuclear MnII complex, the ligands of which contain electron-rich phenols (coordinated to the Mn('s)) and covalently attached ruthenium(II) 2,2′-trisbipyridyl(=bpy)-type groups, intramolecular electron transfer (ET) from the phenolate ligand (in the mononuclear MnIV complex) or from a MnII (in the trinuclear MnII complex) to the photochemically (λexc= 455 nm) generated RuIII takes place with k ≥ 5 × 107 s-1, giving rise to the corresponding phenoxyl radical (complexed to MnIV) or to MnIII, respectively. Thus, in the trinuclear MnII complex, the source of the electron that reduces the photogenerated RuIII(bpy?-) moiety is a MnII, in contrast to the situation with the mononuclear MnIV complex, where the electron stems from a phenolate. The half-life of the coordinated phenoxyl-type Ru(bpy)/Mn complex (as produced in the presence of [CoIII(NH3)5Cl]2+) is of the order 0.5-1 ms. The Ru(bpy) compound containing three (phenolate-ligated) MnII atoms is the first example of a photochemically induced intramolecular ET from a multinuclear Mn cluster to an attached sensitizer , and the Ru complex containing one (phenolate-ligated) MnIV is the first case of an ET from a synthetic MnIV-coordinated phenolate to a photochemically produced oxidant (RuIII).

Mimicking photosystem II reactions in artificial photosynthesis

The paper describes a project aiming at the construction of functional mimics of the oxygen evolving complex of Photosystem II, coupled to photoinduced charge separation. Biomimetic electron donors -manganese complexes and tyrosine -have been linked to a Ru(II)-polypyridine photosensitizer. Oxidation of the donors by intramolecular electron transfer from the photo-oxidized Ru(III) complex was demonstrated using optical flash photolysis and EPR experiments. A step-wise electron transfer Mn → tyrosine → Ru(III) was demonstrated, in a sequence analogous to reactions of the PSII donor side. by Oldenbourg Wissenschaftsverlag, Muenchen.