Mechanisms of synergistic action

Table 2 Mechanisms of synergistic action towards currently used antibiotics hypothesized for catechins and proanthocyanidins...

The combined addition of two phenols, one of which is sterically hindered, for example, 2,6-bis(l,l-dimethylethyl)phenol, and another is sterically nonhindered also leads to a synergistic effect [35-38]. As found by Mahoney [35], 2,4,6-tris(l,l-dimethylethyl)phenol with a concentration of 10 4 L mol 1 does not virtually inhibit the initiated oxidation of 9,10-dihydroan-thracene (333 K), but /)-methoxyphenol, taken in the same concentration, does inhibit oxidation. The induction period doubles if two phenols are added together in equal concentrations, which indicates that both phenols are involved in chain termination. The mechanism of synergistic action can be explained by the following kinetic scheme [35] ... 

It is seen that the substitution of the part of amine or phenol by quinone prolongs the induction period by two or three times. The mechanism of synergistic action of quinone is the same as in the case of nitroxyl radicals. Quinone reacts with InH with production of semiquinone radicals. The latter rapidly reacts with peroxyl radicals and provokes the additional rapid chain termination [47],... 

Most of today s practices are based on empirical data. Further investigation into the mechanism of herbicidal action is of fundamental importance in establishing the use of herbicides on a sound basis. More study into the synergistic effects of combining various chemicals is needed, as well as studies on methods of formulation, optimum quantities, times of application, and the influence of environmental conditions on the herbicidal action. Secondary effects, such as the reported tainting of coffee from 2,4-D deserve further inquiry. 

If the mechanism of cellulase action can be explained simply in terms of sequential action of endo- and exoglucanases, it is logical to expect that Ci from one cellulase preparation should act synergistically with Cx from another, at least in those enzyme systems from which both Cx and Ci have been isolated. Synergism between Ci of P. funiculosum and Cx of T. viride has already been demonstrated (22), and the results in Table V show that "cross-synergism of this type is shown by many different mixtures of the Ci and Cx components of F. solani, T, koningii, and P. funiculosum cellulases. In each case, a marked potentiation in activity is observed. 

In this section, the present view will be outlined of the action of insulin in stimulating the cellular uptake of glucose, and the interference of vanadate in the absence of insulin (diabetes I), insulin tolerance (diabetes II) or as a synergistically insulin-enhancing agent. This will be done on a somewhat simplified basis, amenable to those (including the author) who are less familiar with biochemical depths. For a more detailed discussion, see, e.g., refs 2 and 38a (on the mechanism of the action of insulin) and refs 15, 17 and 18 (include the targeting points of vanadium compounds). Many of the details of... 

Figure 11. Possible mechanism for synergistic action of Ct and Cx on cellulose microfibril...

Loscalzo, 1992). The mechanism of nitrate action on platelets is apparently related to the metabolic production of NO, but some synergistic effect of nitroglycerin with prostacyclin may also exist (Stamler etai, 1989). 

The double whammy—additive detrimental effects and novel adverse reactions Combination therapy takes advantage of synergistic mechanisms of antihypertensive action, but this can also be detrimental, particularly if patients are over-treated, leading to dizziness and orthostatic hypotension. Additive effects of certain combinations can also exacerbate adverse reactions that are common with individual agents. For example, calcium channel blockers and alpha-adrenoceptor antagonists both cause peripheral edema, which can be severe if these agents are used together. 

The inhibitors of oxidation reaction of fats are substances which reduce the oxidation rate, regardless of the mechanism of their action. These compounds include antioxidants, synergists, chelating agents and compounds decomposing hydroperoxides by nonradical reactions. Also agents stabiHsing hydroperoxides may reduce the reaction rate because they inhibit the formation of free radicals. 

Localised attack or fracture due to the synergistic action of a mechanical factor and corrosion... 

The four mechanisms discussed above, of the action of inhibitors remain essentially unchanged. Further work on acetylenic alcohols has indicated that barrier films can form owing to crosslinking by hydrogen bonding and synergistic interactions . Theoretical treatments of the electrochemical... 

These high levels were sporadic and transitory. However, some of them were high enough to have caused phytotoxicity, and more work needs to be done to establish whether herbicides are having adverse effects upon populations of aquatic plants in areas highlighted in this study. It should also be borne in mind that there may have been additive or synergistic effects caused by the combinations of herbicides found in these samples. For example, urea herbicides such as diuron and chlortoluron act upon photosynthesis by a common mechanism, so it seems likely that any effects upon aquatic plants will be additive. Similarly, simazine and atrazine share a common mechanism of action. 

A number of studies have been made of combinations of individual toxic gases. Most of these studies show that the effects of these combinations of toxic gases are simply additive. This has been found empirically for CO and HC1 [52] and for CO and HCN [44], although the mechanisms of action are different. These results can be interpreted as each toxicant taking its toll and acting on a weakened system. The CO-carbon dioxide combination has been claimed to be synergistic [53]. 

Sulfur compounds in combination with peroxyl radical acceptors are often used for the efficient break of hydroperoxide [14]. The mechanism of action of these inhibitory mixtures can, however, be more complex, as demonstrated with reference to a pair of 2,6-diphenylphenol and distearyl dithiopropionate [15]. The combined addition of these compounds with concentrations of 0.05% and 0.3%, respectively, results in an extended inhibitory period during the oxidation of PP (up to 3000 h at 413 K). Sulfide (for instance, (3,(3 -diphenylethyl sulfide) or its products not only break down ROOH, but also reduce the phenoxyl radical. Sulfoxide formed in the reaction of the sulfide with ROOH can react with ArO. Thus, the ability of sulfides and their products to reduce phenoxyl radicals can contribute to their synergistic effect. 

One more mechanism responsible for the synergistic action of two phenols has recently been discovered during the study of disproportionation of phenoxyl radicals [42,43], This reaction is possible only for phenoxyls possessing C—H groups in the ortho- or para-position [43], For instance, 2,4,6-tris(l,l-dimethylethyl)phenoxyl is unable to disproportionate, whereas ionol radicals disproportionate. It was found that the cross-disproportionation of ionol and a-tocopherol radicals occurs much more rapidly than homodisproportionation (323 K [42]) ... 

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