Vitamin metals

In some cases, enzymes require the assistance of coenzymes (cofactors) to ensure the reactions proceed. Coenzymes include vitamins, metal ions, acids, and bases. They can act as transporters or electron acceptors or be involved in oxidation-reduction reactions. At the completion of the reaction, coenzymes are released, and they do not form part of the products. For some reactions that are energetically unfavorable, an energy source provided by the compound adenosine triphosphate (ATP) is needed to ensure the reactions proceed, as shown in the following reactions ... 

In addition to the principal constituents listed in Table 1.1, milk contains several hundred minor constituents, many of which, e.g. vitamins, metal ions and flavour compounds, have a major impact on the nutritional, technological and sensoric properties of milk and dairy products. Many of these effects will be discussed in subsequent chapters. 

The blooming of red-tide phytoplankton causes problems in our local coastal environment. Bloom is believed to be a result of eutrophication or changes in temperature, salinity, vitamins, metals, or conditions that affect the amount of solar radiation reaching the organisms. The combination of these parameters makes prediction of these blooms extremely difficult. Monitoring such parameters as salinity, pH, dissolved oxygen, or light in a continuous fashion is already practical however, we need to measure parameters of phytoplankton in the same real-time manner to predict accurately the cause of these blooms. 

Cobalt compounds have been in use for centuries, notably as pigments ( cobalt blue ) in glass and porcelain (a double silicate of cobalt and potassium) the metal itself has been produced on an industrial scale only during the twentieth century. Cobalt is relatively uncommon but widely distributed it occurs biologically in vitamin B12 (a complex of cobalt(III) in which the cobalt is bonded octahedrally to nitrogen atoms and the carbon atom of a CN group). In its ores, it is usually in combination with sulphur or arsenic, and other metals, notably copper and silver, are often present. Extraction is carried out by a process essentially similar to that used for iron, but is complicate because of the need to remove arsenic and other metals. 

Naturally occurring compounds with carbon-metal bonds are very rare The best example of such an organometallic compound is coenzyme Bi2 which has a carbon-cobalt ct bond (Figure 14 4) Pernicious anemia results from a coenzyme B12 deficiency and can be treated by adding sources of cobalt to the diet One source of cobalt IS vitamin B12 a compound structurally related to but not identical with coen zyme B12... 

Lithium acetyhde also can be prepared directly in hquid ammonia from lithium metal or lithium amide and acetylene (134). In this form, the compound has been used in the preparation of -carotene and vitamin A (135), ethchlorvynol (136), and (7j--3-hexen-l-ol (leaf alcohol) (137). More recent synthetic processes involve preparing the lithium acetyhde in situ. Thus lithium diisopropylamide, prepared from //-butyUithium and the amine in THF at 0°C, is added to an acetylene-saturated solution of a ketosteroid to directly produce an ethynylated steroid (138). 

A variety of other metals and their complexes have been studied for radioprotective activity. Among these are copper glycinate, strontium chloride, ZnNa -diethylenetriaminepentaacetate (ZnDTPA), and selenium, which has been studied because of its relationship to endogenous antioxidant mechanisms, especiaHy GSH peroxidase and vitamin E. 

Because of the time and expense involved, biological assays are used primarily for research purposes. The first chemical method for assaying L-ascorbic acid was the titration with 2,6-dichlorophenolindophenol solution (76). This method is not appHcable in the presence of a variety of interfering substances, eg, reduced metal ions, sulfites, tannins, or colored dyes. This 2,6-dichlorophenolindophenol method and other chemical and physiochemical methods are based on the reducing character of L-ascorbic acid (77). Colorimetric reactions with metal ions as weU as other redox systems, eg, potassium hexacyanoferrate(III), methylene blue, chloramine, etc, have been used for the assay, but they are unspecific because of interferences from a large number of reducing substances contained in foods and natural products (78). These methods have been used extensively in fish research (79). A specific photometric method for the assay of vitamin C in biological samples is based on the oxidation of ascorbic acid to dehydroascorbic acid with 2,4-dinitrophenylhydrazine (80). In the microfluorometric method, ascorbic acid is oxidized to dehydroascorbic acid in the presence of charcoal. The oxidized form is reacted with o-phenylenediamine to produce a fluorescent compound that is detected with an excitation maximum of ca 350 nm and an emission maximum of ca 430 nm (81). 

Because of the presence of an extended polyene chain, the chemical and physical properties of the retinoids and carotenoids are dominated by this feature. Vitamin A and related substances are yellow compounds which are unstable in the presence of oxygen and light. This decay can be accelerated by heat and trace metals. Retinol is stable to base but is subject to acid-cataly2ed dehydration in the presence of dilute acids to yield anhydrovitamin A [1224-18-8] (16). Retro-vitamin A [16729-22-9] (17) is obtained by treatment of retinol in the presence of concentrated hydrobromic acid. In the case of retinoic acid and retinal, reisomerization is possible after conversion to appropriate derivatives such as the acid chloride or the hydroquinone adduct. Table 1 Hsts the physical properties of -carotene [7235-40-7] and vitamin A. 

Hoffmaim-La Roche has produced -carotene since the 1950s and has rehed on core knowledge of vitamin A chemistry for the synthesis of this target. In this approach, a five-carbon homologation of vitamin A aldehyde (19) is accompHshed by successive acetalizations and enol ether condensations to prepare the aldehyde (46). Metal acetyUde coupling with two molecules of aldehyde (46) completes constmction of the C q carbon framework. Selective reduction of the internal triple bond of (47) is followed by dehydration and thermal isomerization to yield -carotene (21) (Fig. 10). 

Vkiyl aHenes (44) are rearranged with heat or metal catalysis and photosensitized isomerization to produce the vitamin D triene (156—160). 

The isophytol side chain can be synthesized from pseudoionone (Fig. 5) using chemistry similar to that used in the vitamin A synthesis (9). Hydrogenation of pseudoionone (20) yields hexahydropseudoionone (21) which can be reacted with a metal acetyUde to give the acetylenic alcohol (22). Rearrangement of the adduct of (22) with isopropenyknethyl ether yields, initially, the aHenic ketone (23) which is further transformed to the C g-ketone (24). After reduction of (24), the saturated ketone (25) is treated with a second mole of metal acetyUde. The acetylenic alcohol (26) formed is then partially hydrogenated to give isophytol (14). 

AH formulations of vitamin E must show low acidity, and contain not more than 0.004% heavy metals (reported as Pb) and not more than 10 ppm Pb. Eormulations that contain RRR-a-tocopherol must have a specific rotation of +24 ° for the oxidation product with alkaline potassium ferricyanide. 

Chelation is a feature of much research on the development and mechanism of action of catalysts. For example, enzyme chemistry is aided by the study of reactions of simpler chelates that are models of enzyme reactions. Certain enzymes, coenzymes, and vitamins possess chelate stmctures that must be involved in the mechanism of their action. The activation of many enzymes by metal ions most likely involves chelation, probably bridging the enzyme and substrate through the metal atom. Enzyme inhibition may often result from the formation by the inhibitor of a chelate with a greater stabiUty constant than that of the substrate or the enzyme for a necessary metal ion. 

Cobalt(II) nitrate hexahydrate [10026-22-9], Co(N02)2 6H20, is a dark reddish to reddish brown, monoclinic crystalline material containing about 20% cobalt. It has a high solubiUty in water and solutions containing 14 or 15% cobalt are commonly used in commerce. Cobalt nitrate can be prepared by dissolution of the simple oxide or carbonate in nitric acid, but more often it is produced by direct oxidation of the metal with nitric acid. Dissolution of cobalt(III) and mixed valence oxides in nitric acid occurs in the presence of formic acid (5). The ttihydrate forms at 55°C from a melt of the hexahydrate. The nitrate is used in electronics as an additive in nickel—ca dmium batteries (qv), in ceramics (qv), and in the production of vitamin B 2 [68-19-9] (see Vitamins, VITAMIN B22)-... 

Chemicals are ubiquitous as air, carbohydrates, enzymes, lipids, minerals, proteins, vitamins, water, and wood. Naturally occurring chemicals are supplemented by man-made substances. There are about 70000 chemicals in use with another 500-1000 added each year. Their properties have been harnessed to enhance the quality of life, e.g. cosmetics, detergents, energy fuels, explosives, fertilizers, foods and drinks, glass, metals, paints, paper, pesticides, pharmaceuticals, plastics, rubber, solvents, textiles thus chemicals are found in virtually all workplaces. Besides the benefits, chemicals also pose dangers to man and the environment. For example ... 

Many enzymes carry out their catalytic function relying solely on their protein structure. Many others require nonprotein components, called cofactors (Table 14.2). Cofactors may be metal ions or organic molecules referred to as coenzymes. Cofactors, because they are structurally less complex than proteins, tend to be stable to heat (incubation in a boiling water bath). Typically, proteins are denatured under such conditions. Many coenzymes are vitamins or contain vitamins as part of their structure. Usually coenzymes are actively involved in the catalytic reaction of the enzyme, often serving as intermediate carriers of functional groups in the conversion of substrates to products. In most cases, a coenzyme is firmly associated with its enzyme, perhaps even by covalent bonds, and it is difficult to... 

The largest industrial use of LiC2H is in the production of vitamin A, where it effects ethynyl-ation of methyl vinyl ketone to produce a key tertiary carbinol intermediate. The acetylides and dicarbides of the other alkali metals are prepared similarly. It is not always necessary to prepare this type of compound in liquid ammonia and, indeed, further substitution to give the bright red perlithiopropyne Li4C3 can be effected in hexane under reflux ... 

The structure of the diamagnetic, cherry-red vitamin B12 is shown in Fig. 26.6 and it can be seen that the coordination sphere of the cobalt has many similarities with that of iron in haem (see Fig. 25.7). In both cases the metal is coordinated to 4 nitrogen atoms of an unsaturated macrocycle (in this case part of a corrin ring which is less symmetrical and not so unsaturated as the porphyrin in haem) with an imidazole nitrogen in the fifth position. A major... 

The important commercial feature of these juices, especially significant with blackcurrant and tomato juices, is their ascorbic acid (or vitamin C) content, of which loss by oxidation is known to be accelerated both by heat and by metal (particularly copper) contamination. The effect of copper has been carefully investigated for pure ascorbic acid", and more recently ascorbic acid in blackcurrant juice and model systems. There are, however, oxidation inhibitors of different kinds (which may themselves be heat-sensitive) present in various fruits, which give differing results. The presence of metals will also affect flavours", may cause discoloration, and may give rise to clouding effects, as in apple juice. ... 

Scheme 1 outlines the retrosynthetic analysis of the Woodward-Eschenmoser A-B variant of the vitamin B12 (1) synthesis. The analysis begins with cobyric acid (4) because it was demonstrated in 1960 that this compound can be smoothly converted to vitamin B12.5 In two exploratory corrin model syntheses to both approaches to the synthesis of cobyric acid,6 the ability of secocorrinoid structures (e. g. 5) to bind metal atoms was found to be central to the success of the macrocyclization reaction to give intact corrinoid structures. In the Woodward-Eschenmoser synthesis of cobyric acid, the cobalt atom situated in the center of intermediate 5 organizes the structure of the secocorrin, and promotes the cyclization... 

---