4,4 -Bipyridylium radicals

D. W. Clack, J. C. Evans, A. Y. Obaid, and C. C. Rowlands, The assignment of the hyperfine coupling constants for the pyridyl protons in aryl and alkyl A-substituted bipyridylium radical cations, Tetrahedron 39, 3615-3620 (1983). 

With respect to using methyl viologen as electron relay, it might be of interest to note tlmt MV " can be oxidized by positive holes produced in illuminated colloidal semiconductors such as Ti02 Two oxidation products of MV are 1, 2 -di-hydro-l,r-dimethyl-2 -oxo-4,4 -bipyridylium chloride and 3,4-dihydro-l,r-dime-thyl-3-oxo-4,4 -bipyridylium chloride, which can readily be detected by their strong fluorescences at 516 nm and 528 nm, respectively. These products are also produced in the direct photolysis of MV " solutions and in the reaction of MV "" with OH radicals in homogeneous solution... 

The production of free radicals has been implicated in the mechanism of liver injury due to a number of drugs and toxins. These include adtiamycin (Pritsos et al., 1992), halothane (Neuberger and Williams, 1984), phenobar-bital and thiopental (Kanazawa and Ashida, 1991), carbon tetrachloride (Williams and Burk, 1990), 1,1,2,2-tetrachloroethane (Paolini aal., 1992), and paraquat and related bipyridylium compounds (Togashi a al., 1990 De Gray etal., 1991 Kanazawa and Ashida, 1991 Petty etal., 1992). 

De Gray, J.A., Rao, D.N. and Mason, R.P. (1991). Reduction of paraquat and related bipyridylium compounds to free radical metabolites by rat hepatocytes. Arch. Biochem. Biophys. 289, 145-152. 

Cyclic photophosphorylation is also a highly energetic reaction. The bipyridyliums, paraquat and diquat (Figure 2.2), divert the electron flow of cyclic photophosphorylation (photosystem I). The capture of an electron from the chlorophyll reduces the herbicide and the reduced herbicide reacts with oxygen to form superoxide. Superoxide produces hydrogen peroxide within the chloroplast and these two compounds interact to form hydroxyl radicals in the presence of an iron catalyst. Hydroxyl radicals are very damaging and lead to the destruction of the cellular components leading to rapid plant death. 

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). 

Electrochromic materials are of three basic types [i]. In a given -> electrolyte solution, type I materials are soluble in both the reduced and oxidized (redox) states, an example being l,l -di-methyl-4,4 -bipyridylium ( methyl viologen ), which, on reduction, switches from the colorless di-cation to the blue radical cation. Type II materials are soluble in one redox state, but form a solid film on the surface of an electrode following electron transfer. An example here is l,l -di-heptyl-4,4 -bipyridylium ( heptyl viologen ). In type III materials, such as -> tungsten oxide, - Prussian blue, and electroactive conjugated polymers, both... 

The initial EPR work on pyridinyl radicals showed that the simplest radicals exhibited fairly complex spectra [4 l,l -dimethyl-4,4 -bipyridylium cation radical 37,60)] jjqJj Nagakura analyzed the spectra of a few simple pyridinyls . Improved methods for generating pyridinyl radicals as well as faster methods of spectroscopic analysis have led to a substantial increase in the information available, including a s tion on hyperfine coupling constants in the handbook, Landolt-Bomstein A review by Symons of EPR in chemistry has appeared. Triplet pyridinyl pairs have also been observed. 

A. L. Rieger and P. H. Rieger, Magnetic resonance studies of some bipyridylium dications and cation radicals,/. Chem. Phys. 88, 5845-5851 (1984). 

Atrazine, a triazine herbicide, blocks electron transport between QA and QB in PSD. DCMU (3-(3,4-dichlorophenyl)-l,l-dimethylurea) also blocks electron flow between the two molecules of plastoquinone. Paraquat is a member of a family of compounds called bipyridylium herbicides. Paraquat is reduced by PSI but is easily reoxidized by 02 in a process that produces superoxide and hydroxyl radicals. Plants die because their cell membranes are destroyed by radicals. Of the herbicides just discussed, determine which, if any, are most likely to be toxic to humans and other animals. What specific damage may occur ... 

The next major class of widely used herbicides is made up of the bipyridi-um compounds, which include paraquat (l,l -dimethyl-4,4 -bipyridylium dichloride) and diquat (l,l -ethylene-2-2 -bipyridylium dibromide). Experimental exposure of animals, or accidental or deliberate exposure of humans to high doses of paraquat, produces respiratory toxicity after 10 to 14 days. Although this polar compound is poorly absorbed after oral delivery, it is actively concentrated in the lung. There it results in necrosis of pulmonary tissue followed by a proliferative phase that ultimately ends in pulmonary fibrosis and end-stage lung disease. The initial toxicity is directed at membranes and is a result of free radical oxidative damage secondary to generation of... 

The bipyridylium free radical is reconverted (oxidised) by the action of oxygen present in the leaf tissues, with the formation of hydrogen peroxide. Oxygen in the leaf tissue is formed during light reaction II by decomposition of water (Zweig and Avron, 1965). 

Whereas cation radicals are formed from neutral molecules by one electron oxidation processes, bipyridylium salts readily give rise to stable cation radicals by one electron reduction processes. Several types of bipyridylium salts have been shown to have interesting herbicidal properties (Akhavein and Linscott, 1968) and the most important of these are exemplified in Scheme 3 by paraquat dichloride (PQ2+) (l,T-dimethyl-4,4 -bipyridylium dichloride) and diquat dibromide (PQ2+ 6,7-dihydrodipyrido[l,2- 2,l,-c]-pyrazine-di-ium dibromide). Herbicidal activity appears to depend, in part, on the ease of (reversible) one electron reduction of PQ2+ and... 

DQ2+ to form stable but air sensitive cation radicals PQ + and DQ + respectively (Dodge, 1971). One electron reduction of bipyridylium salts may be achieved elcctrochemically (Elofson and Edsberg,... 

We have already noted that although disproportionation of bipyridylium cation radicals is a well established phenomenon, the positions of equilibrium for paraquat and diquat lie overwhelmingly to the left hand side of eqn (197) (Hirnig et al., 1973). It is also well... 

The bipyridylium herbicides, used as a substitute for ploughing in erosion-prone country, are contact herbicides. Because they are not appreciably translocated, weeding with them produces a razor-sharp boundary. The most potent of these is paraquat 4.65), l,r-dimethyl-4,-4 -bipyridylium cation (used as the dichloride). This substance has long been in use in another connection, namely as an indicator for low reduction potentials. This colourless substance, known as methyl viologen, functions by forming a violet-coloured stable free radical 4.66) when the potential falls to —446 mV (Michaelis and Hill, 1933). 

The bipyridyl free radicals are not a direct cause of death, but just a stage in a rapid cycle of reduction and re-oxidation. In the course of this cycle much hydrogen peroxide is formed, and some superoxide free radical which is considered to be the true toxic agent (Fridovich, 1975). When monuron (see above) is used to inhibit photosynthesis, diquat loses most of its effect. Although paraquat is completely safe in normal usage, large oral doses cause fibrosis of the lungs, and death may follow. For a book on bipyridylium herbicides, see Summers (1980). 

The bipyridylium herbicides diquat and paraquat, used as an alternative to ploughing, and acting through the formation of free radicals, are described in Section 4.5. 

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