Schiff-base adduct

FIGURE 18.27 Pyridoxal-5-phosphate forms stable Schiff base adducts with amino acids and acts as an effective electron sink to stabilize a variety of reaction intermediates. 

Formaldehyde reacts with proteins to form adducts and cross-links.31516 Metz et al.3 have identified three types of chemical modifications after treatment of proteins with formaldehyde (a) methylol (hydroxymethyl) adducts, (b) Schiff bases, and (c) methylene bridges. The reaction of formaldehyde with proteins is summarized in Figure 19.1, but briefly, formaldehyde reacts primarily with lysine and cysteine to form methylol adducts. The methylol adduct can subsequently undergo a dehydration reaction to form a Schiff base. Adducted primary amine and thiol groups can undergo a second reaction with arginine,... 

The transfer hydrogenation of aldimines has not been reported. In our own studies we have tested the simple Schiff base adduct between benzylamine and benzaldehyde and shown this to be reduced in straightforward manner. 

Gamovskii, A. D. Nivorozhkin, A. L. Minkin, V. 1. Ligand environment and the structure of schiff base adducts and tetracoordinated metal-chelates. Coord. Chem. Rev. 1993,126, 1-69. 

Protein 4-HNE-Modifed Lysine Schiff Base Adduct... 

Weissleder et al. [84] first showed that the human transferrin receptor (hTfR) can be used to internalize MRI contrast agents. The hTfR regulates cellular uptake of iron from transferrin, a plasmatic iron transport protein [85], via a receptor mediated endocytosis mechanism. Thus, MION particles (dextran coated iron oxide) were oxidized with sodium periodate. Holotransferrin was added and the resulting Schiff base adduct was reduced with sodium cyanoborohydride to give transferrin labeled MIONs, Tf-MION (Scheme 3). 

Acetaldehyde may bind to lipids and proteins, principally through the epsilon amino group of lysine, to form unstable acetaldehyde-Schiff base adducts ( adduct , in chemistry a chemical compound that forms from the addition of two or more substances). Although such adducts are unstable and the reaction is readily reversed, further reduction produces a stable Schiff base that is not easily reversed (Figure 7.1). 

Lysyl oxidases catalyze the oxidation of the e-amino group in the side chain of lysine residues in proteins, producing a reactive aldehyde functional group, which can form Schiff-base adducts with unmodified lysine residues or undergo aldol addition, creating covalent cross-links between polypeptide chains. " Lysyl oxidases are widespread in nature, and have been isolated from organisms ranging from yeast to man. 

Cobalt Complexes. A fair number of complexes of cobalt have been studied theoretically. Veillard and co-workers have studied the Schiff base adduct Co(acacen)L02 (L = none, H2O, CO, CN", imidazole) and the porphyrin complex Co(porph)(NH3)02 using ab initio LCAO SCF methods. The calculations show the structure to be more stable than the if a linear structure is also found to be unstable. The most important interaction is that between the cobalt d a orbital and the in- plane rg orbital. The interactions of the in-plane jig orbital with the dyz orbital and TTg (i) with dxz, although present, are much less than in the analogous iron complexes as a result of the tighter binding of the d-orbitals in cobalt. The unpaired electron is localised essentially in the Tig (1) orbital of dioxygen. 

The formation of adducts through a Schiff base mechanism was the basis to assess the reactivity of the seven model compounds with this new technique. The reactivity index generated with our method was consistent with those reported by Benet et al. [26] and Bolze et al. [27] (Table 10.3), which validated this technique to evaluate AG reactivity. Schiff base adducts of AGs and proteins were obtained from the literature for TOL, ZOM, and DCL... 

Glucose is reactive because of the presence of an aldehyde group in its open-chain form. The aldehyde group slowly condenses with amino groups to form Schiff-base adducts. 

Glycation is a posttranslational modification that occurs in vivo by direct chemical reaction between glucose and the primary amino groups of proteins. The initial product is a labile Schiff base adduct, which undergoes a slow Amadori rearrangement to a stable ketoamine derivative of the protein (Fig. 2). 

Fig. 2.3 Reaction of IsoK/LG with primary amines to form stable adducts. Primary amines including lysine react with IsoK/LGs to form a hemiaminal adduct. Unlike most aldehydes which can only form the highly reversible Schiff base adduct, the hemiaminal adduct of y-ketoaldehydes can undergo a second nucleophilic attack to form a pyrrolidine adduct which dehydrates to form an irreversible pyrrole adduct. In the presence of oxygen, the pyrrole is converted to lactam and hydroxylactam adducts. Oxidation of the pyrrole leads to formation of stable crosslinked species...

The reductive half-reaction of methylamine dehydrogenase is shown in Scheme 10. The methylamine substrate initiates a nucleophilic attack on the quinone carbon at the C6 position of the TTQ cofactor displacing the oxygen to form a substrate-TTQ Schiff base adduct (29). The reactivity of the C6 position was demonstrated by covalent adduct formation at this position by hydrazines which are inactivators of methylamine dehydrogenase. Deprotonation of the substrate-derived carbon of 29 by an active-site amino acid residue results in reduction of the cofactor and yields an intermediate in which the Schiff base is now between the nitrogen and substrate-derived carbon (30). Hydrolysis of 30 releases the formaldehyde product and yields the aminoquinol form of the cofactor with the substrate-derived amino group still covalently bound (31). 

---