Glutaraldehyde

Glutaraldehyde is the most popular b/s-aldchydc homobifunctional crosslinker in use today. Flowever, a glance at glutaraldehyde s structure is not indicative of the complexity of its possible reaction mechanisms. Reactions with proteins and other amine-containing molecules would be expected to proceed through the formation of Schiff bases. Subsequent reduction with sodium cyanoborohydride or another suitable reductant would yield stable secondary amine 

Reductive Amination to Secondary Amine Linkage with Terminal Formyl Group 

Hydrazone Linkage with Terminal Formyl Group 

If a small molecule is involved, however, reduction of the hydrazone with sodium cyanoboro-hydride is recommended to produce a leak-resistant bond. 

Bis-epoxy compounds that have been used for crosslinking purposes vary mainly in their chain length, ranging from the 4-carbon bridge of l,2 3,4-diepoxybutane (Skold, 1983 Kohn et al., 1966), the 6-carbon spacer of l,2 5,6-diepoxyhexane (Fearnley and Speakman, 1950), 

Synonyms Cidex (2% alkaline glutaraldehyde aqueous solution) 1,5-pentanedial glutaric dialdehyde glutaral 

Physical Form. Colorless crystalline solid, soluble in water and organic solvents 

As broad-spectrum antimicrobial cold sterilant/disinfectant for hospital equipment as tanning agent for leather as tissue fixative as cross-linking agent for proteins as preservative in cosmetics as therapeutic agent for warts, hyperhidrosis, and dermal mycotic infections in X ray processing solutions and film emulsion as a disinfectant in the beauty industry 

Toxicology. Glutaraldehyde is an irritant of the upper respiratory tract and may be capable of inducing asthma in some individuals it is a skin irritant and can cause an allergic contact dermatitis. 

Glutaraldehyde has caused an allergic contact dermatitis in hospital workers using it as a cold sterilant or in handling recently processed X ray film. It appears to be a strong sensitizer. In general, reactions present as a vesicular dermatitis of the hands and forearms. Rubber gloves do not appear to afford complete protection. In unsensitized individuals it acts as a mild skin irritant. 

General information. Aqueous solutions of formaldehyde are generally used both as biocides and as hydrogen sulfide scavengers in the oilfield. It is very common for formaldehyde to be used in combination with quaternary ammonium compounds, glutaraldehyde and THPS (see 5.4.7.). Solutions of formaldehyde tend to be inexpensive (relative to the other commonly used biocides), so it continues to be widely used. 

Mechanism of action. Formaldehyde mode of action has been extensively studied and is due to its ability to react with several different amino acids. It will react with those amino acids containing sulfhydryl (cysteine), hydroxyl (serine), and amine (lysine, arginine) groups. It is also unique in that it may also react with the purine and pyrimidine groups of both DNA and RNA. The varied nature of formaldehyde s mode of reactivity with all of these functional groups distinguishes it from other aldehydes such as acrolein and glutaraldehyde. 

Compatibility concerns. Formaldehyde will react with and become deactivated by the bisulfite based oxygen scavengers (March, 1992). It will also react with hydrogen sulfide and so systems with microbial contamination and souring will place a high demand on the formaldehyde. In systems where formaldehyde is used in souring control, precipitation problems can occur Walker, 1975). 

General information. Glutaraldehyde is a 5-carbon dialdehyde that has seen extensive use in industrial water treatment applications. In addition to its use as a biocide in oil and gas operations, it is also used in cooling water, paper making, and preservative applications, medical instrument sterilization, and as a non-biocidal crosslinker for leather. X-ray films, and enzyme immobilization. It is often used in oilfield applications in combination with other non-oxidizing biocides such as QAC s and formaldehyde and is compatible with the oxidizing biocides typically used in cooling water applications. 

Mechanism of action. Chemically, glutaraldehyde is 1,5-pentanedial. As an aldehyde, it is a reactive molecule that undergoes those chemical reactions that are typical of any aldehyde. Its applications as a microbicide rely on the fact that it reacts with the free amine (non-protonated) form of primary and secondary amines in an irreversible manner. The pH of the surrounding medium, along with the pKa of the amine, will determine whether an amine is in its protonated or non-protonated (free) form. In acidic solutions, amines are generally protonated and their reaction with glutaraldehyde are slower than in alkaline systems where the amine is not protonated. For this reason, glutaraldehyde works faster in alkaline systems than acidic systems. 

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Vinyl ethers and a,P unsaturated carbonyl compounds cyclize in a hetero-Diels-Alder reaction when heated together in an autoclave with small amounts of hydroquinone added to inhibit polymerisation. Acrolein gives 3,4-dihydro-2-methoxy-2JT-pyran (234,235), which can easily be hydrolysed to glutaraldehyde (236) or hydrogenated to 1,5-pentanediol (237). With 2-meth5lene-l,3-dicarbonyl compounds the reaction is nearly quantitative (238). 

Uses. Union Carbide consumes its vinyl ether production in the manufacture of glutaraldehyde [111-30-8J. BASF and GAF consume most of their production as monomers (see Vinyl polymers). In addition to the homopolymers, the copolymer of methyl vinyl ether with maleic anhydride is of particular interest. 

Acrolein as Diene. An industrially useful reaction in which acrolein participates as the diene is that with methyl vinyl ether. The product, methoxydihydropyran, is an intermediate in the synthesis of glutaraldehyde [111 -30-8]. 

OHCCHjCHjCHjCHO CHO 1 OHCCH2CHCH2CHO glutaraldehyde or pentandial 1,2,3,-propanetricarbaldehyde or formylpentandial [111-30-8] [61703-13-7]... 

Many procedures have been studied for detoxification of aflatoxkis, including heat and treatment with ammonia, methylamine, or sodium hydroxide coupled with extraction from an acetone—hexane—water solvent system. Because ki detoxification it is important to free the toxki from cellular constituents to which it is bound, a stabifi2ation of protekis uskig a tanning compound such as acetaldehyde (qv) or glutaraldehyde may be a solution to the problem (98). 

Immobilization. The fixing property of PEIs has previously been discussed. Another appHcation of this property is enzyme immobilization (419). Enzymes can be bound by reactive compounds, eg, isothiocyanate (420) to the PEI skeleton, or immobilized on soHd supports, eg, cotton by adhesion with the aid of PEIs. In every case, fixing considerably simplifies the performance of enzyme-catalyzed reactions, thus faciHtating preparative work. This technique has been appHed to glutaraldehyde-sensitive enzymes (421), a-glucose transferase (422), and pectin lyase, pectin esterase, and endopolygalacturonase (423). 

Table 1 Hsts representative examples of capsule shell materials used to produce commercial microcapsules along with preferred appHcations. The gelatin—gum arabic complex coacervate treated with glutaraldehyde is specified as nonedible for the intended appHcation, ie, carbonless copy paper, but it has been approved for limited consumption as a shell material for the encapsulation of selected food flavors. Shell material costs vary greatly. The cheapest acceptable shell materials capable of providing desired performance are favored, however, defining the optimal shell material for a given appHcation is not an easy task.

Complex Coacervation. This process occurs ia aqueous media and is used primarily to encapsulate water-iminiscible Hquids or water-iasoluble soHds (7). In the complex coacervation of gelatin with gum arabic (Eig. 2), a water-iasoluble core material is dispersed to a desired drop size ia a warm gelatin solution. After gum arabic and water are added to this emulsion, pH of the aqueous phase is typically adjusted to pH 4.0—4.5. This causes a Hquid complex coacervate of gelatin, gum arabic, and water to form. When the coacervate adsorbs on the surface of the core material, a Hquid complex coacervate film surrounds the dispersed core material thereby forming embryo microcapsules. The system is cooled, often below 10°C, ia order to gel the Hquid coacervate sheU. Glutaraldehyde is added and allowed to chemically cross-link the capsule sheU. After treatment with glutaraldehyde, the capsules are either coated onto a substrate or dried to a free-flow powder. 

Starch is subject to fermentation by many microorganisms and, unless the mud is saturated with salt or the pH is >11.5, a preservative or biocide must be added if the mud is to be used for an extended period of time. The most common biocide until the mid-1980s was paraformaldehyde [9002-81-7]. This material has been largely replaced by isothia2olones (at 5—10 ppm cone) (74), carbamates, and glutaraldehyde [111-30-8]. Alternatively, the biocide may be incorporated during the processing of the starch and is present in the commercial product. 

Disinfection destroys pathogenic organisms. This procedure can render an object safe for use. Disinfectants include solutions of hypochlorites, tinctures of iodine or iodophores, phenoHc derivatives, quaternary ammonium salts, ethyl alcohol, formaldehyde, glutaraldehyde, and hydrogen peroxide (see Disinfectants AND antiseptics). Effective use of disinfected materials must be judged by properly trained personnel. 

The diffusion process has not been designed to ensure sterility, although temperatures above 65°C significantly retard microbial activity. Sulfur dioxide, thiocarbamates, glutaraldehyde, sodium bisulfite, and chlorine dioxide are all used, occasionally disregarding their redox incompatibilities, to knock down or control infections. The most common addition point is to the water from the pulp presses as it is returned to the diffuser. Surfactants ate almost... 

Two types of immobilization are used for immobilizing glucose isomerase. The intracellular enzyme is either immobilized within the bacterial cells to produce a whole-ceU product, or the enzyme is released from the cells, recovered, and immobilized onto an inert carrier. An example of the whole-ceU process is one in which cells are dismpted by homogenization, cross-linked with glutaraldehyde, flocculated using a cationic flocculent, and extmded (42). 

In a second example, a cell—gelatin mixture is cross-linked with glutaraldehyde (43). When soluble enzyme is used for binding, the enzyme is first released from the cell, then recovered and concentrated. Examples of this type of immobilization include binding enzyme to a DEAE-ceUulose—titanium dioxide—polystyrene carrier (44) or absorbing enzyme onto alumina followed by cross-linking with glutaraldehyde (45,46). 

Poly(vinyl alcohol) is readily cross-linked with low molecular weight dialdehydes such as glutaraldehyde or glyoxal (163). Alkanol sulfonic acid and poly(vinyl alcohol) yield a sulfonic acid-modified product (164). 

Two aldehydes (qv) have made their mark in the field of disinfection, namely formaldehyde [50-00-0] and glutaraldehyde [111-30-8]. Other aldehydes do not match these compounds in activity (111,112). 

Caution should be taken when using glutaraldehyde. Gloves and aprons should be worn and adequate ventilation provided. It has been reported to produce contact dermatitis, eye irritation, nausea, headache, rashes, and asthmatic reaction (125). 

Because enzymes can be intraceUularly associated with cell membranes, whole microbial cells, viable or nonviable, can be used to exploit the activity of one or more types of enzyme and cofactor regeneration, eg, alcohol production from sugar with yeast cells. Viable cells may be further stabilized by entrapment in aqueous gel beads or attached to the surface of spherical particles. Otherwise cells are usually homogenized and cross-linked with glutaraldehyde [111-30-8] to form an insoluble yet penetrable matrix. This is the method upon which the principal industrial appHcations of immobilized enzymes is based. 

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