Mechanism of inhibition

Copper Corrosion Inhibitors. The most effective corrosion inhibitors for copper and its alloys are the aromatic triazoles, such as benzotriazole (BZT) and tolyltriazole (TTA). These compounds bond direcdy with cuprous oxide (CU2O) at the metal surface, forming a "chemisorbed" film. The plane of the triazole Hes parallel to the metal surface, thus each molecule covers a relatively large surface area. The exact mechanism of inhibition is unknown. Various studies indicate anodic inhibition, cathodic inhibition, or a combination of the two. Other studies indicate the formation of an insulating layer between the water surface and the metal surface. A recent study supports the idea of an electronic stabilization mechanism. The protective cuprous oxide layer is prevented from oxidizing to the nonprotective cupric oxide. This is an anodic mechanism. However, the triazole film exhibits some cathodic properties as well. 

Silicates. For many years, siUcates have been used to inhibit aqueous corrosion, particularly in potable water systems. Probably due to the complexity of siUcate chemistry, their mechanism of inhibition has not yet been firmly estabUshed. They are nonoxidizing and require oxygen to inhibit corrosion, so they are not passivators in the classical sense. Yet they do not form visible precipitates on the metal surface. They appear to inhibit by an adsorption mechanism. It is thought that siUca and iron corrosion products interact. However, recent work indicates that this interaction may not be necessary. SiUcates are slow-acting inhibitors in some cases, 2 or 3 weeks may be required to estabUsh protection fully. It is beheved that the polysiUcate ions or coUoidal siUca are the active species and these are formed slowly from monosilicic acid, which is the predorninant species in water at the pH levels maintained in cooling systems. 

The mechanism of inhibition has not been characterized, but it is probably related to the ionophoretic properties of these antibiotics. Monensin has been shown to inhibit the intracellular transport of viral membrane proteins of cells infected with Semliki Forest vims (169). The formation of syncytia, normally observed when T-lymphoblastoid cell line (CEM) cells are cocultivated with human immunodeficiency vims (HlV-l)-infected T-ceU leukemia cell line (MOLT-3) cells, was significantly inhibited in the presence of monensin (170). This observation suggests that the viral glycoproteins in the treated cells were not transported to the cell surface from the Golgi membrane. 

Some other inhibitors from the patent literature include hydroquinone [129], ionoP [130], and quinone [131]. Other inhibitors used to stabilize MMA include butylated hydroxy toluene (BHT), phenothiazine, methylene blue, hydroxy-diphenylamine and di-/jc/<3-napthol [132]. Several good reviews of inhibition and inhibitors have been written [133-136]. The mechanisms of inhibition are subtle and complicated. For example, it has been reported that highly purified benzo-quinone acts as a retarder rather than an inhibitor [137]. It has been proposed... 

The mechanism of inhibition by the salts of the long chain fatty acids has been examined . It was concluded that, in the case of the lead salts, metallic lead was first deposited at certain points and that at these points oxygen reduction proceeded more easily, consequently the current density was kept sufficiently high to maintain ferric film formation in addition, any hydrogen peroxide present may assist in keeping the iron ions in the oxide film in the ferric condition, consequently the air-formed film is thickened until it becomes impervious to iron ions. The zinc, calcium and sodium salts are not as efficient inhibitors as the lead salts and recent work has indicated that inhibition is due to the formation of ferric azelate, which repairs weak spots in the air-formed film. This conclusion has been confirmed by the use of C labelled azelaic acid, which was found to be distributed over the surface of the mild steel in a very heterogeneous manner. ... 

Soluble pigments The most important pigments in this class are the metallic chromates, which range in solubilities from 17 0 to 0-00005 g/1 CrO . An examination has recently been carried out of the mechanism of inhibition by chromate ions and it has been shown by chemical analysis of the stripped film, Mdssbauer spectroscopy and electron microprobe analysis that the air-formed film is reinforced with a more protective material in the form of a chromium-containing spinel (Chapter 17). The situation is, however, complicated by the possibility that some chromates, particularly the basic ones, may inhibit through the formation of soaps. There is evidence that lead chromate can function in this way. 

Little work has been carried out on the mechanism of inhibition of the corrosion. of copper in neutral solutions by anions. Inhibition occurs in solutions containing chromate , benzoate or nitrite ions. Chloride ions and sulphide ions act aggressively. There is evidence that chloride ions can be taken up into the cuprous oxide film on copper to replace oxide ions and create cuprous ion vacancies which permit easier diffusion of cuprous ions through the film, thus increasing the corrosion rate. 

Ethanol also inhibits ADH-catalyzed retinol oxidation in vitro, and ethanol treatment of mouse embtyos has been demonstrated to reduce endogenous RA levels. The inhibition of cytosolic RolDH activity and stimulation of microsomal RolDH activity could explain ethanol-mediated vitamin A depletion, separate from ADH isoenzymes. Although the exact mechanism of inhibition of retinoid metabolism by ethanol is unclear, these observations are consistent with the finding that patients with alcoholic liver disease have depletedhepatic vitamin A reserves [review see [2]. 

The kinetics and mechanism of inhibition by stable radicals has been reviewed by Rozantsev el al,lS3 Ideally, for radicals to be useful inhibitors in radical polymerization they should have the following characteristics ... 

Transcription factor DNA-binding motif Groove recognition Proposed mechanism of inhibition... 

There are several examples in which metabolites that toxify the organism responsible for their synthesis are produced. The classic example is fluoroacetate (Peters 1952), which enters the TCA cycle and is thereby converted into fluorocitrate. This effectively inhibits aconitase—the enzyme involved in the next metabolic step—so that cell metabolism itself is inhibited with the resulting death of the cell. Walsh (1982) has extensively reinvestigated the problan and revealed both the complexity of the mechanism of inhibition and the stereospecihcity of the formation of fluorocitrate from fluoroacetate (p. 239). It should be noted, however, that bacteria able to degrade fluoroacetate to fluoride exist so that some organisms have developed the capability for overcoming this toxicity (Meyer et al. 1990). 

J. D. Everard and M. C. Drew. Mechanisms of inhibition of water movement in anaerobically treated roots of Zea mays. Journal of Experimental Botany 38 1154 (1987). 

A major portion of TFPI is bound to the endothelial surface and can be released from the cells by heparin (28). Platelets contain very small amounts of TFPI, which are released when platelets are activated (29). Figure 6 illustrates the mechanism of inhibition by TFPI. 

Fig. 6. Mechanism of inhibition of tissue factor pathway inhibitor (TFPI). Kunitz domain 1 (Dl) inhibits TF-VIIa complex. Domain 2 (D2) inhibits Xa.

Determination of the IC50 is a preliminary evaluation of the relative affinity of different compounds for a target enzyme. To evaluate affinity properly, however, one must first define the mechanism of inhibition of the target enzyme by each compound. The next step in the lead evaluation flowchart (Figure 5.1) is to determine if the inhibition caused by a compound is rapidly reversible, slowly reversible, or irreversible. This information will help the investigator understand whether or not the inhibition reaction can be treated as a reversible equilibrium, and thus decide on the best measure of true affinity for a particular compound. 

Addition of the L-732,531 FKBP binary complex to a calcineurin activity assay resulted in increasingly nonlinear progress curves with increasing binary complex concentration. The htting of the data to Equation (6.3) revealed an inhibitor concentration effect on v-, as well as on vs and obs, consistent with a two-step mechanism of inhibition as in scheme C of Figure 6.3. Salowe and Hermes analyzed the concentration-response effects of the binary complex on v, and determined an IC50 of 0.90 pM that, after correction for I.S I/A (assuming competitive inhibition), yielded a A) value for the inhibitor encounter complex of 625 nM. 

JW Huff, PS Reinach. (1985). Mechanism of inhibition of net ion transport across frog corneal epithelium by calcium channel antagonists. J Membr Biol 85 215-223. 

The possible mechanisms of inhibition of flavin by (—)-deprenyl, as an irreversible acetylenic inhibitor, were studied by ab initio methods with the 6-31G basis set using simplified model compounds, 3-formyl-2-imino-l-hydroxypyrazine, and propargylamine. The formation of two energetically stable cyclic adducts, the 0,N adduct 286 and a C,N adduct, was shown <1999THA147>. 

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