Nitroprussides reduction

Note cautiously the characteristic odour of acetaldehyde which this solution possesses. Then with the solution carry out the following general tests for aldehydes described on p. 341 Test No. I (SchiflF s reagent). No. 3 (Action of sodium hydroxide). No. 4 (Reduction of ammoniacal silver nitrate). Finally perform the two special tests for acetaldehyde given on p. 344 (Nitroprusside test and the Iodoform reaction). 

Aim for a 10-15% reduction in mean arterial pressure (MAP) ° Nitroprusside—0.25-0.5 mcg/kg/min continuous IV infusion increase in increments of 0.25-0.5 mcg/kg/min until desired hemodynamic effect. Usual doses up to 2-3 mcg/kg/min. High-alert medication—read package insert before use... 

The exact nature of the NO-releasing reaction and the other products of reaction in mammalian tissue are still unclear. The matter has been discussed by a number of authors and a reductive mechanism in rat hepatocytes and human erythrocytes has been suggested in the presence of NADH and NADPH. Nitroprusside can pass through cell membranes and so there is no intrinsic difficulty with this suggestion. There is direct evidence from spin echo NMR studies to show the conversion, by nitroprusside, of glutathione into glutathione disulfide within erythrocytes [49]. 

Tolerance to nitrates is defined as the reduction in hemodynamic effect or the requirement for higher doses to achieve a persistent effect with continuous use in the face of constant plasma concentrations [15]. Nitrate tolerance was first described for nitroglycerin in 1888 [36] it occurs with all organic nitrates, albeit to different extents. For reasons that are not understood, PETN appears to be the least susceptible to the development of tolerance. No, or much less, tolerance is observed with nitrite esters, such as amyl nitrite [37], molsidomine, and sodium nitroprusside. Earlier investigations suggested that a depletion of intracellular thiols is involved in tolerance development [17], but this has not been substantiated in later studies [38, 39]. As with organic nitrate bioactivation, the precise mechanism(s) involved in nitrate tolerance remain(s) unknown, but it is likely to be complex and multifactorial. Two principal... 

The therapeutic effects of sodium nitroprusside depend on release of nitric oxide which relaxes vascular muscle. Sodium nitroprusside is best formulated as a nitrosonium (NO+) complex. Its in vivo activation is probably achieved by reduction to [Fe(CN)5NO]3, which then releases cyanide to give [Fe(CN)4NO]2, which in turn releases nitric oxide and additional CN to yield aquated Fe(II) species and [Fe(CN)6]4 (502). There are problems associated with its use, namely reduced activity due to photolysis (501) and its oxidative breakdown due to the action of an activated immune system (503), both of which release cyanide from the low-spin d6 iron complex. 

Ru(CN)jNO reactions with OH , SH and SOj" resemble those of the nitroprusside ion, with attack at the coordinated nitrosyl to give analogous transients and similar second-order rate constants. Ruthenium(II) complexes of the general type Ru(N2), Nj = biden-tate hgands, are important reactants. The relative inertness of Ru(NH3) + and Ru(diimine)f+ towards substitution makes these complexes definite, although weak, outer-sphere reductants (Tables 5.4, 5.5, 5.6 and 5.1). Ruthenium(ll) complexes of the general type Ru(diimine)f +, and particularly the complex Ru(bpy)j+, have unique excited state properties. They can be used as photosensitizers in the photochemical conversion of solar energy. Scheme 8.1 ... 

The kinetics of formation of nitroprusside from [Fe VCN)5(H20)] indicate a mechanism of complex formation in which outer-sphere reduction to [Fe (CN)5(Fl20)] precedes substitution."" Reduction of the dimeric pentacyanoferrate(III) anion [Fe2(CI io]" by thiourea is a multi-stage process the first step is one-electron transfer to give [Fe2(CN)io], which dissociates to give [Fe(CN)5(tu)]2- and [Fe(CN)5(H20)] -.""... 

The drugs of this class (hydralazine and sodium nitroprusside) lower arterial blood pressure primarily by direct spasmolytic action on smooth musculature of arterioles, which leads to a reduction of resistance of peripheral vessels by causing dilation. Diastolic pressure is usually lowered more than the systolic pressure. 

Cyanide poisoning poses some risk however, this is minimized both by the kinetic inertness of both Fe and Fe " cyano complexes and the high affinity of these ions for cyanide ([Fe"(CN)6] , fi6 10 [Fe "(CN)6] , Bg 10 [7, 35]. Small amounts of cyanide, which are released by photolysis and reduction products of nitroprusside, can usually be metabolized in the liver and kidneys by the enzyme rhodanase, which converts CN" to SCN [7, 36]. Cyanide can also be taken up by hydroxocobalamin to generate cy-anocobalamin (B12). As the conversion of cyanide to thiocyanate is dependent on the availability of sulfur, thiosulfate can be administered as an antidote [37]. Monitoring thiocyanate levels as an indicator of cyanide toxicity is no longer routine, but is done on patients with severe hepatic compromise who have been... 

Sodium nitroprusside is the only clinically used metal complex of NO, so that its reactions provide an indication of the types of reactivity that metallonitrosyl complexes might be expected to have in physiological environments (see Fig. 1). The in vivo activation of nitroprusside depends on its reduction to [Fe(CN)5NO], which then releases cyanide to give [Fe(CN)4NO] which in turn releases NO and additional CN to yield Fejl,) and [Fe(CN)g] [75]. [Fe(CN)5(NO)] is paramagnetic (g, = 1.9993, g, = 1.9282, g = 2.008,... 

Thiolates reduce nitroprusside stoichiometrically to yield R2S2 and [Fe(CN)s(NO)] , which can then convert to [Fe(CN)4(NO)] with subsequent release of NO. Reduction may take place through thionitrito adduct formation (see below) followed by generation of the redox products and eventually [Fe(CN)e] or [Fe(CN)5L]" or release of the thionitrite ligand with subsequent decay to the same products [7, 54]. If oxygen is present, nitroprusside is regenerated and can catalyze the air oxidation of thiols, such as cysteine to cystine [91]. 

While nitroprusside itself is substitution inert, the reduction product, [Fe(CN)5(NO)] , rapidly loses the trans cyanide (see above) and [Fe(CN)4(NO)] is substitution labile via a dissociative pathway and is rapidly substituted by chelating diamines to give products such as... 

This electron transfer pathway may partially explain the extraordinarily high efficacy of nitroprusside as it provides single electrons at a sufficiently negative potential to reduce both P450 (E° = — 0.17 to — 0.35 V) [148] and nitroprusside. Since NADPH/P450 reductase has been shown to be an efficient activator of this drug [43], NO may be evolved by NO-synthase reduction of nitroprusside at the same sites where NO is produced physiologically. 

Sodium nitroprusside, which is used for rapid pressure reduction in arterial hypertension, generates NO in response to light as well as chemical or enzymatic mechanisms in cell membranes. See Chapter 11 for additional details. 

It has been known for a long time that nitrosyl complexes can be prepared using nitric acid the nitroprusside ion [Fe(CN)5NO]2 was first obtained by its action on [Fe(CN)6]3-.85 In many cases the production of such species was accidental and the reactions are often quite complex. Several nitrosyls of the platinum metals have been obtained in this way and recently the polymeric species Pt4(MeC02)6(N0)2 was isolated, together with other products, from the reduction of PtIV in a mixture of nitric and acetic acids.57... 

Abbreviations CEL, cellulose DXM, dexamethasone EIPA, ethylisopropylamiloride FIB, fibrin MR methylprednisolone NA, not available Neo-R, neointima reduction PC, phosphorylcholine PCL, polycaprolactone PFM-P75, polyfluoroalkoxyphosphazene PLLA(PLA), poly-L-lactic acid POP, polyorganophosphazene PU, polyurethane Q-DL, Quanam drug eluting stent Q-M, Quanam metal stent SNR sodium nitroprusside TIMP, tissue inhibitors of metalloproteinase. 

The characteristic colours and solubilities of many metallic sulphides have already been discussed in connection with the reactions of the cations in Chapter III. The sulphides of iron, manganese, zinc, and the alkali metals are decomposed by dilute hydrochloric acid with the evolution of hydrogen sulphide those of lead, cadmium, nickel, cobalt, antimony, and tin(IV) require concentrated hydrochloric acid for decomposition others, such as mercury(II) sulphide, are insoluble in concentrated hydrochloric acid, but dissolve in aqua regia with the separation of sulphur. The presence of sulphide in insoluble sulphides may be detected by reduction with nascent hydrogen (derived from zinc or tin and hydrochloric acid) to the metal and hydrogen sulphide, the latter being identified with lead acetate paper (see reaction 1 below). An alternative method is to fuse the sulphide with anhydrous sodium carbonate, extract the mass with water, and to treat the filtered solution with freshly prepared sodium nitroprusside solution, when a purple colour will be obtained the sodium carbonate solution may also be treated with lead nitrate solution when black lead sulphide is precipitated. 

Sulphate, (i) BaCl2 solution and dilute HC1 test, and reduction to sulphide test for latter with sodium nitroprusside or lead acetate solution (IV.24, 1). (ii) Lead acetate test and solubility of PbS04 in ammonium acetate solution (IV.24, 2). 

Sodium nitroprusside in solution is extremely photosensitive, undergoing rapid and numerous photodegradation reactions (69). The deterioration of the product is evidenced by a color change from brown to blue, resulting from the reduction of the ferric ion to the ferrous ion. Hydrogen cyanide is one of the toxic degradation products formed. Therefore, reconstituted solutions should be stored protected from UV-VIS radiation by wrapping the container with aluminium foil or some other opaque material. Solutions with adequate photoprotection are stable for up to 24 hours (70-72). 

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