Glutaraldehyde reaction mechanism

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... 

Amino groups on proteins may be reacted with the bis-aldehyde compound glutaraldehyde to form activated derivatives able to cross-link with other proteins. The reaction mechanism for this modification proceeds by one of several possible routes. In the first option, one of the aldehyde ends can form a Schiff base linkage with e-amines... 

The kinetics of the catalytic oxidation of cyclopentene to glutaraldehyde by aqueous hydrogen peroxide and tungstic acid have been studied and a compatible mechanism was proposed, which proceeds via cyclopentene oxide and /3-hydroxycyclopentenyl hydroperoxide. " Monosubstituted heteropolytungstate-catalysed oxidation of alkenes by t-butyl hydroperoxide, iodosobenzene, and dioxygen have been studied a radical mechanism was proved for the reaction of alkenes with t-BuOOH and O2, but alkene epoxidation by iodosobenzene proceeds via oxidant coordination to the catalyst and has a heterolytic mechanism. ... 

Four nurses who were sterilizing endoscopes with glutaraldehyde developed symptoms of asthma and rhinitis temporally related to exposures to glutaraldehyde. Three of the four nurses, however, had a prior history of mild seasonal asthma." On specific provocation testing, one patient had an increase in nasal airway resistance, with a dual immediate and late response pattern. Another patient had a delayed 22% decline in FEVi 80 minutes after the final exposure to glutaraldehyde. The occurrence of late reactions suggested that the underlying mechanism involved sensitization rather than an irritant effect." ... 

Glutaraldehyde is a homobifunctional cross-linker containing an aldehyde residue at both ends of a 5 carbon chain. Its primary reactivity is toward amine groups, but the reaction may occur by more than one mechanism. As discussed in Chapter 4, Section... 

A major disadvantage of the gel entrapment route to immobilization is the potential for physical loss of the enzyme as time elapses. To circumvent this problem, cross-linking agents, such as A,A -methylene-bis-acrylamide or glutaraldehyde, may be used to more firmly immobilize the enzyme or to provide mechanical stability. However, the more rigid the matrix the greater is the possibility that diffusional resistance to transport of reactants (substrates) to the site of the enzyme and of products out of the gel will limit the reaction rate. 

It seems that the pharmacological activities showed by different iridoids are due to their genine, like aucubin. The structural similarity between the aglycone and glutaraldehyde suggests a similar mechanism of enzyme inhibition through protein cross-linking by Schiff reactions. 

The glutaraldehyde and hydrazine reactions are used for matrices having amide groups such as polyacrylamide. Glutaraldehyde and hydrazine react with the polymer, and the enzyme or protein is readily bound to the treated polymer. The mechanism of the reactions involved in the activation and coupling are not well understood. In general, insoluble supports such as polyacrylamide, which tend to swell in water, form immobilized proteins or enzymes when mixed with a solution and treated with... 

Cheung, D.T. and Nimni, M.E. (1982). Mechanism of crosslinking of proteins by glutaraldehyde I Reaction with model compounds. Connective Tissue Research, 10, 187-199. 

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