Inhibiters, chain-breaking

The early work of Kennerly and Patterson [16] on catalytic decomposition of hydroperoxides by sulphur-containing compounds formed the basis of the preventive (P) mechanism that complements the chain breaking (CB) process. Preventive antioxidants (sometimes referred to as secondary antioxidants), however, interrupt the second oxidative cycle by preventing or inhibiting the generation of free radicals [17]. The most important preventive mechanism is the nonradical hydroperoxide decomposition, PD. Phosphite esters and sulphur-containing compounds, e.g., AO 13-18, Table la are the most important classes of peroxide decomposers. 

There has been some evidence of a higher antioxidant effect when both flavonoids and a-tocopherol are present in systems like LDL, low-density lipoproteins (Jia et al., 1998 Zhu et al, 1999). LDL will incorporate a-tocopherol, while flavonoids will be present on the outside in the aqueous surroundings. A similar distribution is to be expected for oil-in-water emulsion type foods. In the aqueous environment, the rate of the inhibition reaction for the flavonoid is low due to hydrogen bonding and the flavonoid will not behave as a chain-breaking antioxidant. Likewise, in beer, none of the polyphenols present in barley showed any protective effect on radical processes involved in beer staling, which is an oxidative process (Andersen et al, 2000). The polyphenols have, however, been found to act synergistically... 

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],... 

We thought that the resumption of oxidation after a few min was likely due to the depletion of NO since subsequent additions of NO inhihited oxidation with kinetics similar to the first addition. In order to prove this, we repeated the experiment, hut this time determined the [ NO] at periodic time intervals. We initiated the experiment with 20 pM and then added 0.9 pM NO 1 min later. At this 1 min time point, oxidation was inhihited (Figure 3). This inhibition continued until about 4.5 min, which is about when the [ NO] fell to below the limit of detection. At this time there was still sufficient Fe (7.2 pM) to reinitiate oxidation. These results demonstrate that NO is acting as a chain-breaking antioxidant during cellular lipid peroxidation. 

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. ... 

Synergistic behavior by two antioxidants is not confined to compounds which inhibit by entirely different mechanisms—for example, two chain-breaking phenolic antioxidants may synergize one another. This homosynergism is caused by the suppression of the unfavorable chain propagation reactions of one phenoxy radical by a hydrogen atom transfer from the second phenol. 

The mechanisms of inhibition by peroxide decomposers, metal deactivators, and ultraviolet absorbers are fairly well understood in general terms, although many details of the individual reactions remain to be elucidated. Classifying a preventive antioxidant into one of the three categories above will only rarely describe its entire function. The dual behavior of dialkyl dithiophosphates in the liquid phase has been mentioned. Many other phosphorus- and sulfur-containing antioxidants commonly classified as peroxide decomposers can also act as chain breakers. Similarly, the structure of many metal deactivators and ultraviolet absorbers indicates that they must also have some chain-breaking activity. 

Among chain-breaking antioxidants the stable dialkyl nitroxides such as di-f erf-butyl nitroxide (I) and 2,2,6,6-tetramethyl-4-pyridone nitroxide (II) inhibit oxidation by the simplest mechanism and therefore exhibit... 

They do not react with R02 radicals. The inhibited oxidation rate is proportional to the oxygen pressure and inversely proportional to the nitroxide concentration, but it is independent of the substrate concentration—i.e., rate oc [02]/[nitroxide]. The nitroxides react slowly with hydrocarbons and hydroperoxides and therefore have little tendency to initiate oxidation. However, they are of disappointingly little practical value compared with more conventional chain-breaking antioxidants because they must compete with molecular oxygen for the R radicals, and the... 

The radical addition and hydrogen transfer mechanisms of inhibition by chain-breaking antioxidants are now reasonably well understood in both qualitative and quantitative terms. The electron-transfer mechanism of inhibition deserves greater attention. 

The kinetics of the zinc diisopropyl dithiophosphate-in-hibited oxidation of cumene at 60°C. and Tetralin at 70°C. have been investigated. The results cannot be accounted for solely in terms of chain-breaking inhibition by a simple electrow-transfer mechanism. No complete explanation of the Tetralin kinetics has been found, but the cumene kinetics can be explained in terms of additional reactions involving radical-initiated oxidation of the zinc salt and a chain-transfer step. Proposed mechanisms by which zinc dialkyl dithiophosphates act as peroxide-decomposing antioxidants are discussed. 

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 conclusion that chain-breaking inhibition by zinc dialkyl dithiophosphates involves electron transfer was reached independently by Burn (6) following a more detailed qualitative study of the inhibition of the azonitrile-initiated oxidation of squalane and cumene and the noninitiated oxidation of indene by metal dialkyl dithiophosphates and related compounds (I to IV) ... 

The radical (RO)2PS2 in indene would thus effectively act as a chaincarrying radical and is therefore not considered to be an intermediate in chain-breaking inhibition by dithiophosphates. A two-stage mechanism was therefore proposed, involving a stabilized zinc salt-peroxy complex, either a radical or an ion pair as illustrated in structures V and VI. 

The present paper reports the results of a kinetic study of the inhibition of the azobisisobutyronitrile-initiated autoxidation of cumene at 60 °C. and of Tetralin at 70 °C. by zinc diisopropyl dithiophosphate, undertaken to test the validity of the chain-breaking inhibition mechanism proposed above. In addition, the effectiveness of several metal dialkyl dithiophosphates as antioxidants in the autoxidation of squalane... 

Chain-Breaking Inhibition Mechanism. According to the mechanism proposed earlier (6), the inhibition of the autoxidation of a hydrocarbon... 

Biological antioxidants such as a-tocopherol (65, vitamin E) serve to inhibit free radical chain oxidation, and the mechanisms of their reactions have attracted close attention. The chain-breaking reaction of such phenols with peroxyl radicals is by hydrogen transfer (equation 101). 

The inhibition of lipid (LH) oxidation may be considered as one of the most important chemical reaction mechanisms that could explain the antioxidant function of flavonoids. In general terms, chain-breaking antioxidants (AH) inhibit or retard lipid oxidation (reactions 1-7) by interfering with initiation [generically represented by reaction 1] or with chain propagating reactions (reactions 2 and 3) by readily donating hydrogen atoms to lipid peroxyl radicals (LOO ) or lipid radicals (L ) (reactions 4 and 5) [Frankel, 1998] ... 

We will not go in depth into the subject of antioxidants (12), which is more a part of preformulation than a stress test, but the autoxidation mechanism does suggest that oxidation can be inhibited by peroxy radical scavengers (chain-breaking antioxidants) like phenol antioxidants, by heavy metal chelating agents, and by peroxide inactivating substances (preventive antioxidants). 

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