Paraquat structure

Cationic compounds Bipyridinium herbicides such as Diquat and Paraquat (Structures I-II, Fig. 3) are the only important compoimds of this group that have been thoroughly investigated [89-91 ]. They are available as dibromide and dichloride salts, respectively, and are used as herbicides and desiccants. These compounds were shown to be toxic to humans [92-94]. The solubility of cationic pesticides is generally high in aqueous solutions, where they dissociate readily to form divalent cations. 

Structural formulas of paraquat cation (upper) and paraquat dichloride salt (lower)... 

Lajmanovich, R.C., M.F. Izaguirre, and V.H. Casco. 1998. Paraquat tolerance and alteration of internal gill structure of Scinax nasica tadpoles (Anura Hylidae). Arch. Environ. Contam. Toxicol. 34 364-369. 

Seto, Y. and T. Shinohara. 1988. Structure-activity relationship of reversible cholinesterase inhibitors including paraquat. Arch. Toxicol. 62 37-40. 

FIGURE 8.25 Redox cycle of paraquat leading to the production of superoxide anion and a similar structure formed by oxidation of MPTR... 

The herbicide paraquat is structurally similar to MPP". Paraquat is toxic since it can generate superoxide free... 

Figure 14.16 A proposed mechanism by which MPTP can result in Parkinson s disease. MPTP is l-methyl-4-phenyltetrahydropyridine and is oxidised to MPP (l-methyl-4-phenylpyridinium). This is the agent that destroys dopaminergic neurones. Note the similarity between the structure of MPP and paraquat...

Paraquat (1,1 dimethyl, 4,4 bipyridyl) is a nonselective contact herbicide. It is used almost exclusively as a dichloride salt and usually is formulated to contain surfactants. Both its herbicidal and toxicological properties are dependent on the ability of the parent cation to undergo a single electron addition, to form a free radical that reacts with molecular oxygen to reform the cation and concomitantly produce a superoxide anion. This oxygen radical may directly or indirectly cause cell death. Diquat, l,T-ethylene-2,2 -dipyridylium, is a charged quaternary ammonium compound often found as the dibromide salt. The structure of diquat dibromide and that of the closely related herbicide paraquat can be seen in Fig. 4.5. 

Much can also now be done to predict molecular structures which give these properties on the basis of partition relationships and knowledge of additive molecular characteristics such as paraquat. These principles are illustrated with specific examples. 

The X-ray crystal structures (Figure 7) of 6-[Diquat] and 9-[Paraquat] demonstrate that complex formation is aided not only by [C—H O] hydrogen bonding and [N O] electrostatic interactions but also by charge transfer stabilization between the ir electron rich aromatic rings in the molecular receptors and the ir electron deficient bipyridinium rings in the substrates. 

Figure 7. Model representations of the X-ray crystal structures of (a) 6-[Diquat] [Paraquat]. ... 

Toner PG, Vetters JM, Spilg WGS, et al Fine structure of the lung lesion in a case of paraquat poisoning. J Pathol 102 182-185, 1970... 

The quaternary ammonium compounds paraquat and diquat are widely used non-selective contact herbicides, which are extremely toxic to humans. Fee et al. [112] established an HPLC-MS-MS procedure for the determination of these herbicides in whole blood and urine using ethyl paraquat as internal standard. After extraction with Sep-Pak C18 cartridges, analytes were separated using ion pair chromatography with heptafluorobutyric acid in 20 mM ammonium acetate and acetonitrile gradient elution. Detection was carried out in ESI MS-MS SRM mode. Using similar separation and detection conditions, paraquat, diquat, difenzoquat, and a number of structurally related quaternary nitrogen muscle relaxants (see Section 20.2.1.3) were determined in whole blood by Ariffin and Anderson [113]. 

R groups. The unexpected positive AS values for smaller R groups point to a stronger solvent shell which has to be removed on dimerisation. Therefore, a face to face structure of the dimer similar to (76sem)2 has been proposed in accordance with conclusions from the UV-spectra of Paraquat in aequous solution The stretched structure of isEM seems to be important since the radical cation derived from Diquat (2R2sem) does not dimerize ... 

As active transport uses a carrier system, it is normally specific for a particular substance or group of substances. Thus, the chemical structure of the compound and possibly even the spatial orientation are important. This type of transport is normally reserved for endogenous molecules such as amino acids, required nutrients, precursors, or analogues. For example, the anticancer drug 5-fluorouracil (Fig. 3.6), an analogue of uracil, is carried by the pyrimidine transport system. The toxic metal lead is actively absorbed from the gut via the calcium transport system. Active uptake of the toxic herbicide paraquat into the lung is a crucial part of its toxicity to that organ (see chap. 7). Polar and nonionized molecules as well as lipophilic molecules may be transported. As active transport may be saturated, it is a zero-order rate process in contrast to passive diffusion (Fig. 3.3). 

Swager and coworkers also applied the self-assembly process in side-chain systems [131, 132]. The bisphenylene crown ether was incorporated into a conjugated backbone, polyphenyleneacetylene 87. This polymer complexes with paraquat 88 to give a novel polyrotaxane structure (89). With a polythiophene backbone, a similar polyrotaxane was synthesized by the same approach. 

The herbicidal activity of the bipyridyliums depends on their redox properties. Their abilities as one-electron acceptors of the right redox potential (-350 mV for diquat and -450 mV for paraquat) allow them to siphon electrons out of the photosynthetic electron-transport system, competing with the natural acceptors. The radical anion produced is then reoxidized by oxygen, generating the real toxicant, hydrogen peroxide, which damages plant cells. Structure-activity relationships in this series have been reviewed (60MI10701). 

Distinct differences in cells with regard to the presence or absence of target structures or metabolic processes also offer opportunities for selectivity. Herbicides such as phenylureas, simazine, and so on, block the Hill reaction in chloroplasts, thereby killing plants without harm to animals. This is not always the case because paraquat, which blocks photosynthetic reactions in plants, is a pulmonary toxicant in mammals, due apparently to analogous free-radical reactions (see Figure 18.4) involving enzymes different from those involved in photosynthesis. 

As shown by the structures in Figure 15.9, a bipyridilium compound contains two pyridine rings per molecule. The two important pesticidal compounds of this type are the herbicides diquat and paraquat other members of this class of herbicides include chlormequat, morfamquat, and difenzoquat. Applied directly to plant tissue, these compounds rapidly destroy plant cells and give the plant a frostbitten appearance. However, they bind tenaciously to soil, especially the clay mineral fraction, which results in rapid loss of herbicidal activity so that sprayed fields can be planted within a day or two of herbicide application. 

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