Mechanisms of aldehydes

Mechanisms of aldehyde oxidation are not firmly established, but there seem to be at least two main types—a free-radical mechanism and an ionic one. In the free-radical process, the aldehydic hydrogen is abstracted to leave an acyl radical, which obtains OH from the oxidizing agent. In the ionic process, the first step is addition of a species OZ to the carbonyl bond to give 16 in alkaline solution and 17 in acid or neutral solution. The aldehydic hydrogen of 16 or 17 is then lost as a proton to a base, while Z leaves with its electron pair. 

FIGURE 4.30 Mechanism of aldehyde dehydrogenase-mediated oxidation of aldehydes. 

Heck H Mechanisms of aldehyde toxicity Structure activity studies. CUT Activities 5(10) 106, 1985... 

Scheme 2 Racemization Mechanism of Aldehydes through Keto-Enol Tautomerism1"1...

The Mechanism of Aldehyde-Induced ATPase Activities of Kinases... 

On the basis of studies of the reactions of formaldehyde, acetaldehyde and butyraldehyde with ethylzinc diphenylamide as a model catalyst of moderate effectiveness, Van der Kerk [279] revealed the mechanism of aldehyde coordination polymerisation by means of organozinc catalysts ... 

Mechanisms of Aldehyde Oxidation. There must be at least two paths for oxidation of aldehyde to acid, and at least one of these must be temperature dependent. One pathway is the ozone-oxygen oxidation of aldehydes to peracids (14). However, peracid can also serve as an oxidizing agent for aldehyde. In the oxidation of acetaldehyde, Reaction 3 is thought to occur (14). 

The exceptions are chloramines of valine, leucine, and isoleucine, which form semistable chloramines that remain in the reaction medium for several hours (Z4). The mechanism of aldehyde formation from the intermediary amino acid a-chloramines produced either by HOC1 treatment or by the MP0-H202-C1- system was recently verified with use of NMR spectra. The study made possible the identification of short-lived products of the reaction, and confirmed the role of the unstable monochloramine of the a-amino group as the intermediate (H12). 

Biotransformations of nitroglycerin, (a) Normal mechanism of aldehyde reductase (b) production of nitrite by mitochondrial aldehyde dehydrogenase. 

The mechanism of aldehyde formation proceeds in steps that involve cob(II)alamin and cob(III)alamin in significant ways. The initial reaction of the 5 -deoxyadenosyl radical with molecular oxygen leads directly to the 5 -peroxyadenosyl radical (Figure 5), which accepts an electron from cob(II)alamin to form cob(III)alamin and 5 -peroxyadenosine. Ligation of cob(III)alamin by 5 -peroxyadenosine leads to 5 -peroxyadenosylcobal-min, which decomposes to adenosine-5-aldehyde and aquocob(III)alamin. Thus, cob(III)alamin efficiently catalyzes the transformation of 5 -peroxyadenosine into adenosine-5 -aldehyde. In the absence of cob(III)alamin, 5 -peroxyadenosine undergoes spontaneous transformation into adenosine-5-aldehyde at a very slow rate, but the presence of aquocob(III)alamin increases the rate by more than 200-fold. ... 

Two advantages of CA[Mn] are a broader substrate range and the lack of aldehyde side products. CA[Mn] catalyzed epoxidation of fran.y-P-niethyl styrene (46% ee), but this substrate was not oxidized by CPO [57], We did not detect any aldehyde side products in the CA[Mn] catalyzed epoxidations. In contrast, the CPO and CiP-catalyzed epoxidation of styrene formed 24% [57] and 52% [55] benzaldehyde side product. These aldehyde side products form simultaneously with epoxide during styrene epoxidation catalyzed by heme peroxidases [55]. Althongh the mechanism of aldehyde formation is nnknown, this simultaneous formation of aldehyde suggests that it forms from a reaction intermediate of epoxidation. Since the mechanism of epoxidation for the CA[Mn] percarbonate reaction differs from that for the heme peroxidases, this different mechanism may account for the lack of aldehyde side products. 

SCHEME 11.5 Proposed mechanism of aldehyde or ketone elimination following Meisenheimer rearrangement of fert-amine A-oxides. 

The mechanism of aldehyde decarbonylation is thought to follow the established mechanism for acyl halide decarbonylation discussed in the previous section (Equation 7, where A = H). Several observations support this idea, even though intermediates are much more labile than those of the acid chloride system. 

Dunn MF, Biellmann J, Branlant G (1975) Roles of zinc ion and reduced coenzyme in horse liver alcohol dehydrogenase catalysis. The mechanism of aldehyde activation. Biochemistry 14 3176-3182 Dworschak RT, Plapp BV (1977) pH, isotope, and substituent effect on the interconversion of aromatic substrates catalyzed by hydroxy-butylimidylated liver alcohol dehydrogenase. Biochemistry 16 2716-2725... 

Mechanism of Aldehyde Oxidation by Triose Phosphate Dehj drogenase 179... 

Fig. 11.11. Enzymatic formation mechanism of aldehydes and Ce alcohols, responsible for grassy flavors (Crouzet, 1986). (1) [Acyl]hydrolase (2) lipoxygenase in the presence of oxygen (3) peroxide cleavage enz3me (4) alcohol dehydrogenase...

The second type of reaction, recently reviewed by Cheftel (1977), is the carbonyl-amino reaction of the Maillard type with the aldehydes and ketones being formed by breakdown of the peroxides. Malonaldehyde is one such aldehyde formed from the peroxides of linoleic, arachidonic and other oxidised fatty acids such a bifunctional aldehyde can also produce crosslinkages in the protein. The exact reaction mechanism of aldehydes is little understood but they tend to react primarily with the -amino groups of lysine. Cystine... 

Some enzymes require nonprotein cofactor molecules for catalysis, as with NAD mentioned above. A cofactor may be covalently bound to the enzyme, such as FAD in the case of GOx, but others are diffusing freely in solution. Figure 9.3 shows the mechanism of aldehyde dehydrogenase (ALDH), in which an aldehyde is oxidized to a carboxylic acid in conjunction with an NAD cofactor [28]. The NAD cofactor simultaneously binds in the enzyme active site and is released as the reduced form NADH. In this case, NAD acts as the oxidizing substrate of the enzyme and is regenerated back to NAD elsewhere in the system, independently of ALDH. Thus, NAD and other freely diffusing redox cofactors may be thought of as natural mediators. Pyrroloquinohne quinone (PQQ) is another frequently encountered redox cofactor. 

Lei, B., Cho, K.W., and Tu, S.-C., Mechanism of aldehyde inhibition of Vibrio harveyi luciferase. Identification of two aldehyde sites and relationship between aldehyde and flavin binding, /. Biol Chem., 269, 5612, 1994. 

Hardwick JA, Baines KM (2010) Probing the mechanism of aldehyde additimi to a disilene and two silenes solvent effects. Organometallics 29 1305... 

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