Inhibitors solubility

The use of soluble inhibitors as a means of controlling bimetallic corrosion presents many technical problems. Apart from the fact that this method is limited in applicability to recirculating systems, efficient anodic inhibitors, such as chromates, are frequently quite specific in their action and so certain bimetallic couples, such as the Al-Cu couple in chloride solutions, are... 

The effect of various types of inhibitors with respect to structure and solubility on the formation of N-Nitrosodiethanolamine was studied in a prototype oil in water anionic emulsion, Nitrosation resulted from the action of nitrite on diethanolamine at pH 5.2-5.A, Among the water soluble inhibitors incorporated into the aqueous phase, sodium bisulfite and ascorbic acid were effective. Potassium sorbate was much less so. The oil soluble inhibitors were incorporated into the oil phase of the emulsion. 

Evidence exists that the relative solubility of amines and inhibitors in heterogeneous oil-water systems could be decisive in formation of nitrosamines and blocking these reactions, Nitrosopyrrolidine formation in bacon predominates in the adipose tissue despite the fact that its precursor, proline, predominates in the lean tissue (5,6,7). Mottram and Patterson (8) partly attribute this phenomenon to the fact that the adipose tissue furnishes a medium in which nitrosation is favored, Massey, et al, (9) found that the presence of decane in a model heterogeneous system caused a 20-fold increase in rate of nitrosamine formation from lipophilic dihexylamine, but had no effect on nitrosation of hydrophilic pyrrolidine. Ascorbic acid in the presence of decane enhanced the synthesis of nitrosamines from lipophilic amines, but had no effect on nitrosation of pyrrolidine. The oil-soluble inhibitor ascorbyl palmitate had little influence on the formation of nitrosamines in the presence or absence of decane. 

In experiments with water-soluble inhibitors, the subsample was stirred under nitrogen during post-addition of an aqueous solution of the inhibitor followed by an aqueous sodium nitrite solution. Aliquots were weighed into 1-oz ointment jars, covered with nitrogen, sealed, and stored at 37 for later replicate analyses. Preparation of the positive control subsample was identical except that water was added in place of inhibitor. 

Since post-addition of oil-soluble inhibitors would not assure their presence in the oil phase of the emulsion, separate emulsions were prepared. 

In the first set of experiments, it was found that two out of the three oil soluble inhibitors had little effect on the amount of NDEIA formed. It was considered possible that these had broken down during heating at 75 . To rule out this possibility, the oil-soluble inhibitors were added to the oil phase... 

Experimental Results. The inhibition of NDEIA formation after days at 37 forthree water-soluble and three oil-soluble inhibitors is displayed in Tables II and III, respectively. So that relative effectiveness could be compared, the concentration of each inhibitor was chosen to provide an inhibitor/nitrite mole ratio = 10, Each inhibitor was tested in two separate emulsion batches with two or more aliquots analyzed. The data shown for positive controls are from similar replicate experiments. 

Since a-tocopherol destroys nitrite in the system in absence of the oil phase, we may postulate that the ineffectiveness of these two oil soluble inhibitors resulted from their absence from the aqueous phase. Diethanolamine is miscible with water and presumably its nitrosation occurs in the aqueous phase. There is a significant difference in the solubility characteristics of ascorbyl palmitate. The reducing portion of the molecule is water soluble. Thus the ascorbate moiety may be in the aqueous phase while the fatty acid tails may lie within the oil globules. The a-tocopherol and the BHA may well be effective if they are dispersed in the aqueous phase after preparation of the emulsion. This will be investigated in future experiments. 

Inhibitors may be classified according to their solution properties as either oil-soluble inhibitors, water-soluble inhibitors, or dispersible inhibitors. Chemical inhibitors act as film formers to protect the surface of the pipeline. Corrosion inhibitors, used for the protection of oil pipelines, are often complex mixtures. The majority of inhibitors used in oil production systems are nitrogenous and have been classified into the broad groupings given in Table 11-4. Typical corrosion inhibitors are shown in Table 11-5. For details, see also Chapter 6. 

As with caspase-3, these hits were converted into potent, soluble inhibitors by replacing the disulfide linkage with a simple alkyl linkage (Fig. 9.10). As in the case of caspase-3, rigidifying the linker could improve affinity, as could introducing a hydrophobic moiety at the S2 position. Several of these molecules demonstrated activity in cellular assays and selectivity for caspase-1 over the closely related caspase-5. Crystallography of several of these molecules in complex with caspase-1 revealed that they bind in an extended conformation as expected, but that the S2 pocket that collapses in caspase-3 remains open in caspase-1. 

FIGURE 6.6. Schematic depiction of the screening assay for monitoring ligand-receptor interactions on a supported fluid lipid bilayer in the presence of a library of soluble inhibitors. Surface specific observation is achieved using TIRFM. 

Ettmayer, P. Billich, A. Hecht, P. Rosen-wirth, B. Gstach, H. Paracyclophanes a 357 novel dass of water-soluble inhibitors of HIV proteinase./. Med. Chem. 1996, 39, 3291—3299. 

Barton et al. [232] conducted the emulsion polymerization of the sparingly water-soluble monomer St and of the fairly water-soluble monomer MMA in the presence and absence of the water-soluble inhibitor, potassium nitrosodi-sulfonate (Fremy s salt). By using oil-soluble dibenzoyl peroxide (DBP) and water-soluble ammonium peroxodisulfate (APS) as the free-radical initiators, they examined the effect of the location of the initiator on the kinetics of these emulsion polymerizations with SDS as the emulsifier. Figure 7 shows an example of the experimental results. 

Houseman et al. prepared a peptide chip by Diels-Alder-mediated reaction of kinase-peptide substrates with a self-assembled monolayer of alkanethiolates on gold surface. Peptide phosphorylation was determined by incubating the peptide microarrays with c-src protein-tyrosine kinase followed by quantitation with a phos-phoryl imager. In the presence of soluble inhibitors at a range of concentrations, dose-dependent inhibition of phosphorylation against a number of peptide substrates could be determined on a single chip. ... 

Since emulsion polymerization is initiated in the aqueous phase, the undesirable formation of latex polymer can be minimized in suspension systems by using water-soluble inhibitors, like sodium nitrite. 

Aqueous Solubility is Critical to Success. Both early in SBDD and later on in clinical development, sufficient aqueous solubility is critical. Solubility is important early because the concentrations of compounds must be high during crystallization experiments to saturate the high levels of protein. The ratio of the solubility to the inhibition constant of a compound is also critical to the success of the crystallization experiment. Once some structural information becomes available, both parameters can be manipulated, but usually, soluble inhibitors must be available before the availability of structural information. Solubility matters during animal testing and later in... 

Several routes exist for the synthesis of amides of halo acids. Cuatrecasas et al. (1969) used two different bromoacetylating reagents in the synthesis of water soluble inhibitors of staphylococcal nuclease. The N-hydroxysuccinimide ester of bromoacetate was one of the reagents used. It is particularly useful for the synthesis of radioactive derivatives since C-bromoacetic acid is commercially available. Synthesis of the hydroxysuccininimide ester is accomplished by dissolving 87 mg (630 /imoles) of bromoacetic acid and 86 mg of N-hydroxysuccinimide in 3 ml of dioxane. To this solution, 132 mg (700 /imoles) of dicyclohexylcarbodiimide is added. Urea precipitates immediately and after 1 hr, is removed. The solution of bromoacetyl N-hydroxysuccinimide ester is brought to 5 ml. It can then be used without any further purification. 

Ancillary Testing of Inhibitor Resin Properties. It was found that inhibitor could be introduced fairly readily in the two part liquid system either by direct dissolution in the resin or hardener or, for some of the less soluble inhibitors, as a fine dispersion in the resin. Introduction in powder transfer moulding resins was achieved by ball milling the inhibitor with the powder. Subsequent analysis of samples of powder showed that the inhibitor had been uniformly dispersed. 

Two types of soluble binding protein have been described, nonspecific serum proteins and cytokine-specific soluble receptor proteins. The major nonspecific serum protein capable of binding cytokines appears to be a2-macroglobuIin (B57, B58, Mil). A number of soluble cytokine inhibitors related to the relevant receptor have been described. The soluble form of the IL-2R a chain has been found in the serum of apparently normal individuals and is increased in the serum of individuals with inflammatory diseases such as rheumatoid arthritis (W31). Similar molecules have been described for IL-1, IL-6, IFNy, and IL-7 (F7, N14, S62). The mechanism of release has not been properly established but appears to require proteolytic cleavage of the membrane-bound receptor. Soluble inhibitors for two other cytokines, IL-4 and TNF, appear to be derived by alternative RNA splicing sites that give rise to receptors lacking a transmembrane sequence and that are secreted (M50, S22). 

Corrosion control by pigments relies on well-known principles of corrosion inhibition. Iron and steel exposed to air are quickly covered by an oxide film aqueous electrolytes tend to break down this film, and further oxidation of the metal surface ensues. The role of anodic corrosion inhibitors is to supplement or to aid in the repair of the surface oxide film. Basic pigments may form soaps, for example, with linseed oil autoxidation of these soaps may yield soluble inhibitors in the film. Some other pigments of limited solubility act directly as inhibitors. Active metal pigments supply electrons to the iron substrate and thus lower its potential and prevent metal dissolution. 

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