Chain-breaking inhibitors

Scheme 2 Bolland-Gee scheme of free radical oxidation of polymer pH. P denotes macromolecular chain, InH is chain-breaking inhibitor, D peroxide decomposer and parameters above arrows are the corresponding rate constants.

Inhibitors slow down oxidation by breaking chains or breaking down hydroperoxide. The inhibitory action of an antioxidant ceases when it is completely consumed. The duration of inhibitory effect depends on the mechanism of action of the antioxidant, the nature of inhibitory reactions, and the occurrence of side reactions in which the inhibitor is uselessly consumed. The action of the antioxidant in a given system can expediently be characterized in terms of inhibitory capacity. The capacity of a chain-breaking inhibitor can be characterized by the inhibition stoichiometric coefficient f[ 18]. 

The duration of the inhibition period of a chain-breaking inhibitor of autoxidation is proportional to its efficiency. Indeed, with an increasing rate of chain termination, the rates of hydroperoxide formation and, hence, chain initiation decrease, which results in the lengthening of the induction period (this problem will be considered in a more detailed manner later). It should be noted that when initiated oxidation occurs as a straight chain reaction, the induction period depends on the concentration of the inhibitor, its inhibitory capacity, and the rate of initiation, but does not depend on the inhibitor efficiency. 

A combined addition of a chain-breaking inhibitor and a hydroperoxide-breaking substance is widely used to induce a more efficient inhibition of oxidative processes in polyalkenes, rubbers, lubricants, and other materials [3 8]. Kennerly and Patterson [12] were the first to study the combined action of a mixture, phenol (aromatic amine) + zinc dithiophosphate, on the oxidation of mineral oil. Various phenols and aromatic amines can well serve as peroxyl radical scavengers (see Chapter 15), while arylphosphites, thiopropionic ethers, dialkylthio-propionates, zinc and nickel thiophosphates, and other compounds are used to break down hydroperoxide (see Chapter 17). Efficient inhibitory blends are usually prepared empirically, by choosing such blend compositions that induce maximal inhibitory periods [13],... 

More recently it has been shown (6, 7) that zinc dialkyl dithiophosphates also act as chain-breaking inhibitors. Colclough and Cunneen (7) reported that zinc isopropyl xanthate, zinc dibutyl dithiocarbamate, and zinc diisopropyl dithiophosphate all substantially lowered the rate of azobisisobutyronitrile-initiated oxidation of squalene at 60°C. Under these conditions, hydroperoxide chain initiation is negligible, and it was therefore concluded that inhibition resulted from removal of chain-propagating peroxy radicals. Also, consideration of the structure of these zinc dithioates led to the conclusion that no suitably activated hydrogen atom was available, and it was suggested that inhibition could be accounted for by an electron-transfer process as follows ... 

The oxidation of hydrocarbons, reactions (1), (la), (2)—(4), is inhibited to an extent that depends on the efficiency of chain termination, reactions (5), (6), (8)—(10), on the possibility of chain transfer and regeneration, reactions (lb), (5) and (7), and on the possibility of degradation of hydroperoxides to inert products, reaction (11). Amines and phenols are known to be efficient chain breaking inhibitors, while sulphides promote reaction (11). 

Ag(I) is believed to act as an inhibitor, as is likely in the U(IV)-l-02 reaction, by bringing about a chain-breaking step with U(V) the well-defined induction period is proportional to the initial Ag(I) concentration. During this time, a... 

Figure 1 The theoretical plot of induction time of oxidation determined for wr — 0, (zero rate of initiation according to reaction 1 of Scheme 1) on composition of the mixture of inhibitors InH (chain-breaking antioxidant) and D (peroxide decomposer) having the total sum of concentrations 0.01 mol/l. The curve 2 below is the plot of induction times for the same values of parameters as for line 1 but w, = 5 x 10-8 mol/l. The initial concentration of hydroperoxides was 0.001 mol/l.

Substituted-l-naphthols are the most potent 5-hpoxygenase inhibitors known. 2-PhenylteUuro-l-naphthol inhibits stimulated LTB4 biosynthesis in human neu-hophiles, and acts as a catalytic peroxide decomposer as well as a catalytic chain-breaking antioxidant. ... 

An antioxidant ties up the peroxy radicals so that they are incapable of propagating the reaction chain or to decompose the hydroperoxides in such a manner that carbonyl groups and additional free radicals are not formed. The former, which are called chain-breaking antioxidants, free-radical scavengers, or inhibitors. are usually hindered phenols or amines. The latter, called peroxide decomposers, are generally sulfur compounds or... 

Fire is a chain process. It can be stopped by breaking this chain. Scavengers are used to stop the free radical chain reactions and subsequently fire is extinguished. Halogenated compounds are usually good chain-reaction inhibitors. 

If the inhibitor is able to destroy more than one radical (as described below for chain-breaking redox antioxidants) then the efficiency of inhibition will be increased by this ratio. 

Two problems remain. What is the nature of the weak links and what is the mechanism of chain breaking corresponding either to the intercept or to the normal scission process (kt) The second problem has been partly solved by performing the degradation in the presence of a large excess of 1,4-diaminoanthraquinone (DAA) [74]. The molecular weight decrease is not affected by this inhibitor the values of k and P are both unchanged. If the intercept P was due to chain end initiated rupture, followed by random transfer reaction, and subsequent scission at a new radical centre, P would be decreased by the addition of DAA. It thus seems most... 

Effects of Synthetase Inhibitors on the Repair of y-Ray-Induced DNA Chain Breaks... 

A plot of 1/V vs I/Kj will be linear in a cell if the substrate concentration is unchanged by the inhibitors. The plot vill be colinear for a family of inhibitors if they all act on the same enzyme in a cell and if the inhibitors all have equal access to the enzyme. If one makes the assumption that poly(ADP-ribose) synthesis is rate limiting for the repair of DNA chain breaks, then the Kj for a particular synthetase inhibitor will be directly proportional to its for blocking repair. In this case, a plot of the reciprocal of the repair rate vs inhibitor concentration normalized against its Kj for synthetase would be linear and similar plots for a variety of compounds that block repair via blocking synthetase would be colinear. 

Since quantitation of the absolute number of DNA chain breaks is difficult, we chose to express the number of breaks in terms of rad equivalents of DNA breaks [5]. A standard curve was constructed of the first order DNA elution rate through filters under alkaline conditions [5]. Cells were irradiated at doses of 7-rays from 0 to 1000 rad. A plot of the DNA elution rate constant was linear up to 800 rad. Next, the amount of time necessary to repair 400 rad equivalents of DNA damage was determined. The repair rate was linear for about 7. 5 min with completion of repair taking 10 min. We chose a time of 5 min at which time about 50% of the repair of 400 rad was accomplished in cells not exposed to synthetase inhibitors. HeLa cells were irradiated for 400 rad then incubated for 5 min in the presence or absence of synthetase inhibitors to permit DNA repair to be accomplished. Inhibitors utilized were 3-acetamidobenzamide (AAB, = 0.25 ijM), 3-aminobenzamide (AB, = 2.8 [jM), 3-methoxybenzamide (MB, = 0.41 juM), 3-hydroxybenzamide (HB, = 1.05 nM), benzamide (B, = 0.91 iM), and 3-nitrobenzamide (NB, = 1.03 iM) as deter-... 

In fact, the loss of viability is at least as clearly related to the synthetase potency of the compounds as is the relationship to inhibition of 7-ray induced chain break repair - with five of six compounds giving superimposable plots of cloning efficiency vs inhibitor concentration normalized against its Kj for synthetase. As was true for the results in Fig. 1, NB was more effective in reducing cloning efficiency than predicted based on its Kj for synthetase. 

To inhibit the oxidation process, certain chemical compounds (antioxidants or stabilisers) are added to the polyethylene, see Sect. 5.2.2. The so-called chain-breaking-donors or primary antioxidants, also called inhibitors, react with the chemical radicals. They thus intermpt the reaction chain. The so-called hydroperoxide decomposer or secondary antioxidants react with the hydroperoxide before it can disintegrate into radicals. Thus they prevent the start of new reaction chains. 

The use of phenolic and amino-based antioxidants (ie, thermal stabilizers) by this approach has been limited because they inhibit the free-radical polymerization process (polymerization inhibitor) leading to lower efficiency. One of the few commercial products produced is based on the polymerizable chain breaking antioxidant (AO 12b, Table 3), designed for NBR rubbers (Chemigum HR 665) that has been shown to offer superior antioxidant performance, especially imder aggressive (hot oil/high temperature) conditions, compared to low molecular mass conventional aromatic amine antioxidants (165). In spite of the successful synthesis and copoljmierization of a large number of reactive antioxidants, there is a lack of major commercial development and production of antioxidant systems... 

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