Quinon-hydroquinone inhibitors

In the case of mechanism (6) there are materials available which completely prevent chain growth by reacting preferentially with free radicals formed to produce a stable product. These materials are known as inhibitors and include quinone, hydroquinone and tertiary butylcatechol. These materials are of particular value in preventing the premature polymerisation of monomer whilst in storage, or even during manufacture. 

Polymerization inhibitors stop or slow down polymerization by reacting with the initiator or growing-chain radicals. A wide variety of substances can behave as inhibitors quinones, hydroquinones, aromatic nitro compounds, aromatic amines, and so on. In cases where the inhibitor is a hydrogen donor (symbolized here by InH), then for inhibition to occur, the radical resulting from hydrogen transfer (In-) must be too stable to add to monomer. If it does add to monomer and starts a new chain, chain transfer occurs instead of inhibition. For perfect inhibition, the In- radicals must combine with themselves (or initiator radicals) to give inert products ... 

Figure 6.4 Influence of the charge transfer resistance on the current-potential curve. The current-potential curves were measured in the redox system quinon-hydroquinon on a mercury electrode after adding different inhibitors, triangles, no inhibitor, squares, methylene blue, and rhomboids, lauryl acid (0.5 mol-dm NaF, 0.05 mol dm NaH2P04/Na2HP04, pH 6.55, and 10 mol-dm inhibitor). ...

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... 

Methyl Methacrylate CH2=C(CH3)COOCH3 Impure Methyl-Methacrylate Vap in Air 2.1 to 12.5% > Ambient > 110 Inhibitor-Hydroquinone or Methyl Ether of Hydro-quinone. Shield from light avoid sparks. Store in cool place 13.3-13.8 421 Self-polymerizing initiated by visible light at 20 to 40°... 

Hydroquinone often is used as a monomer stabilizer. In the absence of oxygen it is not an inhibitor, however, and its action in the presence of oxygen is the result of its oxidation to quinone. See Ref. 98. 

Phenols, quinones and aromatic amines reduce the rate of polymerisation by reacting with polymer radical. They lose a hydrogen readily but resultant radicals are not initiators. Inhibitors are added to monomers to prevent polymerisation during storage. Hydroquinone and t-butylcatechol in 0.001 to 0.1 per cent concentration act as inhibitors. 

Each ion-radical reaction involves steps of electron transfer and further conversion of ion-radicals. Ion-radicals may either be consnmed within the solvent cage or pass into the solvent pool. If they pass into the solvent pool, the method of inhibitors will determine whether the ion-radicals are prodnced on the main pathway of the reaction, that is, whether these ion-radicals are necessary to obtain the hnal prodnct. Depending on its nature, the inhibitor may oxidize the anion-radical or reduce the cation-radical. Thns, quinones are such oxidizers whereas hydroquinones are reducers. Because both anion and cation-radicals are often formed at the first steps of many ion-radical reactions, qninohydrones— mixtures of quinones and hydroquinones—turn out to be very effective inhibitors. Linares and Nudehnan (2003) successfully used these inhibitors in studies on the mechanism of reactions between carbon monoxide and lithiated aromatic heterocycles. 

Most monomers can be stored unchanged under nitrogen only for short times (hours or days), even in the dark at low temperature. For long-term storage, a suitable stabilizer is therefore indispensable. Effective stabilizers (inhibitors) of radical polymerization are quinones, phenols, amines, nitro compounds, and some metals or metal compounds. The addition of 0.1 to 1 wt% of hydroquinone or 4-ferf-butylpyrocatechol results in sufficient stabilization of many monomers. 

On the other hand, hydroquinone (3 pmol/L) prevented the staurosporine-induced apoptosis of HL-60 and the IL-3-dependent murine myeloblastic (32D) cell line it also prevented apoptosis of the 32D cells observed in the absence of IL-3. The myeloperoxidase inhibitor indomethacin opposed the effect of hydroquinone on staurosporine-induced apoptosis of HL-60 cells (Hazel et al., 1995, 1996b). Pretreatment of human leukaemia cells ML-1 with buthionine sulfoximine (100 pmol/L for 24 h), in order to decrease their glutathione content, increased the susceptibility of these cells to hydroquinone-induced inhibition of differentiation caused by phorbol acetate pretreatment with l,2-dithiole-3-thione, which induces reduced glutathione synthesis, prevented the differentiation inhibition of hydroquinone. Treatment of DBA/2 mice with 1,2-dithiole-3-thione, which increased the activity of quinone reductase of bone-marrow stromal cells by 50%, decreased the susceptibility of these cells towards hydroquinone (Trush et al., 1996). 

The Q-cycle mechanism requires the presence of two separate quinone binding sites that are in contact with different sides of the membrane the hydroquinone oxidation (Q or Qp) site at the positive P side of the membrane and the quinone reduction (Q or Qn) site at the negative N side of the membrane. These sites have first been characterized by their different inhibitor binding properties [2] (see below) the existence of two distinct quinone binding sites was confirmed by the X-ray structure of the bc complex [3-6]. 

Methyl Acrylate CH2=CHC00CH3 Non-inhibitors such as Biphenyl, Bibenzyl, Tri-phenyl, etc Methyl Acrylate Vap plus air > Ambient > 120 Inhibitor—Hydroquinone or Methyl Ether of Hydro-quinone 10-20ppm. Store Store below 10° no inert atmosphere. No sparks 18.58-18.8 463 Self polymerizing above ambient press temp accelerates polymerization... 

Some reagents react with the initiating radical to give unreactive substances, a process known as inhibition. A common inhibitor for vinyl polymerisations is hydroquinone, which reacts by the transfer of two hydrogen radicals to the initiator radicals (Fig. 2.4). This gives quinone and unreactive initiator and has the net effect of causing a lag time in the polymerisation and a decrease in the initiator concentration. Monomers are often stored in the presence of inhibitor in order to prevent polymerisation. The amount and type of inhibitor may vary depending on the monomer batch and the manufacturer. For inter-laboratory comparisons of materials to be possible, it is therefore important to remove the inhibitor and purify the monomers prior to use [13]. 

The inhibitor radicals formed in the above reactions are stabilized by resonance to such an extent that they do not start chains and initiate polymerization. They disappear partly through disproportionation (forming quinone and hydroquinone) ... 

Hydroquinone and other dihydroxybenzenes such as t-butyl catechol also act as inhibitors, but only in the presence of ojqrgen. The inhibiting effect is due to their oxidation to quinone. A large number of other substances are also active inhibitors. These include oxygen, NO (one of the most effective inhibitors, so much so that some highly reactive monomers can be distilled... 

This concept has been extended. Thus the trione (696) rapidly and irreversibly inactivates human erythrocyte nucleoside phosphorylase (PNPase), which catalyzes the reversible phosphorylation of inosine and guanosine to the respective bases and ribose 1-phosphate. Inhibitors of this enzyme have several potential medical applications, for example, in the prevention of foreign tissue rejection, in the treatment of gout and malaria, and for the potentiation of antineoplastic nucleosides. Mechanistically the 5,8-dione (quinone) (696) enters the enzyme active site. An active-site nucleophilic residue subsequently converts the quinone moiety to a hydroquinone by reductive addition (701). The resulting hydroquinone affords an alkylating quinone methide species by elimination of HCl (702) and then traps a second nucleophilic enzyme residue by a Michael type reaction (703). Cross-linking of the active site rationalizes the observed potency <91B8480>. 

Unwanted radicals in biological systems must be destroyed before they have an opportunity to cause damage to cells. Cell membranes, for example, are susceptible to the same kind of radical reactions that cause butter to become rancid (Section 26.3). Imagine the state of your cell membranes if radical reactions could occur readily. Radical reactions in biological systems also have been implicated in the aging process. Unwanted radical reactions are prevented by radical inhibitors—compounds that destroy reactive radicals by creating unreactive radicals or compounds with only paired electrons. Hydroquinone is an example of a radical inhibitor. When hydroquinone traps a radical, it forms semiquinone, which is stabilized by electron delocalization and is, therefore, less reactive than other radicals. Furthermore, semiquinone can trap another radical and form quinone, a compound whose electrons are all paired. 

In connection with a study of a number of anticancer compounds which, presumably also act as inhibitors of free-radical polymerization, eight classes of compounds were studied as to their inhibitory properties. The classes studied were unsaturated hydrocarbons, phenolic compounds, quinones, amines, stable free-radicals, sulfiir compounds, carbonyl compounds, and metallic salts. The most effective inhibitors, of those evaluated, were cupric acetate and cupric resinate, followed by /runs-1,3,5-hexatriene, hydroquinone, benzoquinone, and diphenylamine as modest inhibitors. Among the low-activity inhibitors were 2,2-diphenyl-1-picrylhydrazyl, benzene thiol, and crotonaldehyde [70]. 

A mixture of inhibitors is commonly employed for the styrene diluent in order to obtain a balance of properties in respect of color, storage stability, and gelation rate of catalyzed resin. Thus, a typical composition of the diluent based on the above polyester formulation would be styrene 172 parts, benzyltrimethylammonium chloride 0.44 part, hydroquinone 0.06 part, and quinone 0.006 part. After cooling to the ambient temperature, the resin is transferred into drums for storage and shipping. 

Some of the materials which have been used to stabilize ethers and inhibit formation of peroxides include the addition of 0.001% of hydroquinone or diphenylamine, polyhydroxyl-phenols, aminophenols, and arylamines. Addition of 0.0001 g of pyrogallol in 100 cc ether was reported to prevent peroxide formation over a period of 2 years. Water will not prevent the formation of peroxides in ethers, and iron, lead, and aluminum will not inhibit the peroxidation of isopropyl ether, although iron does act as an inhibitor in ethyl ether. Dowex- 1 has been reported effective for inhibiting peroxide formation in ethyl ether, 100 parts per million (ppm) of 1-naphthol for isopropyl ether, hydroquinone for tetrahydrofuran, and stannous chloride or ferrous sulfate for dioxane. Substituted stilbene-quinones have been patented as a stabilizer against oxidative deterioration of ethers and other compounds. 

The effect of quinones has already been discussed. In industry, quinones are often added as stabilizors to monomers, that is, they are added to prevent premature polymerizations during storage. Hydroquinone is first oxidized to quinone by oxygen, thus removing oxygen before it can produce hydroperoxides with the monomer. Finally, the benzoquinone formed acts as inhibitor. Hydroquinone itself is neither an inhibitor nor a retarding agent. 

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