Fungicides copper dithiocarbamates

The traditional copper fungicides are in fact inorganic copper coordination compounds The still most important group of organic protectant fungicides, the dithiocarbamates, are applied in the form of their metal-coordination compounds. Dimethyldithiocarbamate as the iron complex ferbam and the zinc complex ziram, ethylenebisthiocarbamate as the zinc complex zineb and the manganese complex maneb. 

They can react with metal-containing enzymes (e.g., polyphenoloxidase and ascorbic acid oxidase) to form a copper-dithiocarbamate complex with high fungicidal activity (thiram and ziram probably owe their fungicidal activity to this type of reaction). 

Structurally related compounds, dithiocaibamates (XIV), have fungicidal activity. Reversed-phase chromatography of copper dithiocarbamates was studied, and the Revalues were found to be linearly dependent on the chain length of the chelate, the water content of the mobile phase, and the number of carbon atoms of the chemically bonded stationary phase (93). 

Phinney, J. T. and Bruland, K. W. (1997). Trace metal exchange in solution by the fungicides Ziram and Maneb (dithiocarbamates) and subsequent uptake of lipophilic organic zinc, copper and lead complexes into phytoplankton cells, Environ. Toxicol. Chem., 16, 2046-2053. 

About 100 fungicides me required for these various uses in the United States. The principal ones are sulfur, liine-sulfur (polysulfides of calcium) copper sulfate (or ils equivalent in the oxides, basic sulfates, oxychloride and other relatively insnluhle copper compounds) creosote products and zinc chloride, both used as wood preservatives and a wide variety of organic compounds. Among the latter are several dithiocarbamates. such as ferbam and zineb, and other thio compounds, like N-(trichloronielhyllhio>-phthalimide (folpel) cis-NfI Irtchloroniclhy] Jthio)-4-cyclohexane- 1.2-dicaiboxyimide (captan) and 8-hydroxyquinoline. 

Once the fungicides penetrate to the cell membrane or into the cytoplasm they may operate by devious means to disrupt vital functions. There is substantial evidence that the quinones immobilize the sultliydryl and imino prosthetic group of enzymes. The 8-hydroxyquinoline and dithiocarbamate compounds are active against copper and other metallic members of an enzyme system, presumably hy their ability to chelate metals. Heavy metals such as mercury alTect certain enzymes such as amylases and may serve as general protein precipitants. 

These are easily prepared by the reaction of amines with carbon disulfide (1) in the presence of alkali (Scheme 17).2 The synthesis of dithiocarba mates (4) was first reported by Debus in 1850. Dithiocarba mates (4) form metal chelates, and sodium dimethyl dithiocarbamate is used in quantitative inorganic analysis for the estimation of metals, e.g. copper and zinc. Dithiocarba mates are also employed as vulcanisation accelerators and antioxidants in the rubber industry, and as agricultural fungicides.3 The parent dithiocarbamic acids are unstable, decomposing to thiocyanic acid and hydrogen sulfide however, the salts and esters are stable compounds. Dithiocarba mates (4) are oxidised by mild oxidants to the thiuram disulfides (38) (Scheme 17). 

The fungicidal properties of dithiocarbamates, like thiram, are probably associated with their ability to chelate with essential trace metals such as copper and zinc. Additionally, the 1 1 metal chelates are themselves fungicidal with the ability to penetrate lipid barriers in the fungal cell, and are probably the ultimate toxicants in these fungicides.3 Alkyl esters of dithiocarbamic acids are readily prepared by treatment of sodium dithiocarbamate (4) with the appropriate alkyl halide (Scheme 20). 

Penicillamine (D-(3,(3-dimethylcysteine) is an effective chelator of copper, mercury, zinc and lead which promotes the excretion of these metals in the urine. It is clinically used in patients with Wilson s disease, with rheumatoid arthritis and with heavy-metal intoxications. Ziram and ferbam are the zinc and the iron salts respectively of dimethyl-dithiocarbamic acid (Figure 20.44). They are widely used as selective fungicides in agriculture. Pyrithione (1 -hydroxy-2(l//)-pyridinethione), as its zinc salt is used in dermatology as antiseborrheic. 

Most fungicides developed for plant disease control before 1965 are multisite biochemical inhibitors that lack the chemical properties and biological specificity required for internal therapeutic action in higher plants. This group of plant protectants include such compounds as the Inorganic copper fungicides, captan, chlorothalonil, dithiocarbamates and chlorinated quinones. 

Derivatives of thiocarbamic acid are a family of very important fungicides used in many plant-care products. Manganese salts (maneb), zinc salts (zineb), sodium and iron salts have no action on aluminium, whatever their degree of dilution. On the other hand, copper salts of dithiocarbamic acid may attack aluminium. 

Dithiocarbamates have also been widely used as fungicides. When released into the environment they degrade within days via acid-catalyzed hydrolysis. Recent work has shown that the presence of trace amounts of copper(ll) salts can increase half lives to >2 weeks, irrespective of pH, and it has been suggested that if Me2NCS2 was complexed to copper(II) before release into natural waters, it may be more persistent (1784). 

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