Imide bond

Carboxylic acids may be covalently modified with adipic acid dihydrazide or carbohydrazide to yield stable imide bonds with extending terminal hydrazide groups. Hydrazide functionalities don t spontaneously react with carboxylate groups the way they do with aldehyde groups (Section 4.5, this chapter). In this case, the carboxylic acid first must be activated with another compound that makes it reactive toward nucleophiles. In organic solutions, this may be accomplished by using a water-insoluble carbodiimide (Chapter 3, Section 1.4) or by creating an intermediate active ester, such as an NHS ester (Chapter 2, Section 1.4). 

Alternatively, the use of dipeptide isosters mimicking the cis- or tram-imide geometry 30 or replacement of the imide bond with Z- or E-alkene units131-36 (see also Section 10.5) have been proposed. 

Imide Bond Formation with Terminal Hydrazide Group (a hydrazide-activated protein)... 

The proteinoids are inactivated by heating in buffer solution or by treatment with alkali at room temperature, and it is proved that the hydrolysis of cyclic imide bonds, in which aspartic acid residues are initially bound, accompanies the inactivation by heat8). 

Syn peptide bonds are primarily found in bends or turns and for syn imide bonds the high correlation suggests a specific role for these bonds in turn struc-... 

Fig. 1.2.5. The helix nucleating properties of AcHel depend on the two conformational states of the N-terminal imide bond.

Peptidyl-propyl cis-trans isomerase Foldase Interconversion of peptidyl-propyl imide bonds cypB FKBP22... 

Malomamide (MAM). The MAM molecule is somewhat different from the other model molecules used in this study. MAM contains two amid bonds, while PIM, BPIM and MPIM contain imide bonds. Therefore, it still is useful to compare the adsorption of MAM and its interaction with the Cu surface with the behaviour of the imide model molecules. 

The enzymes of the nucleic acid metabolism are used for several industrial processes. Related to the nucleobase metabolism is the breakdown of hydantoins. The application of these enzymes on a large scale has recently been reviewed [85]. The first step in the breakdown of hydantoins is the hydrolysis of the imide bond. Most of the hydantoinases that catalyse this step are D-selective and they accept many non-natural substrates [78, 86]. The removal of the carbamoyl group can also be catalysed by an enzyme a carbamoylase. The D-selective carbamoylases show wide substrate specificity [85] and their stereoselectivity helps improving the overall enantioselectivity of the process [34, 78, 85]. Genetic modifications have made them industrially applicable [87]. Fortunately hydantoins racemise readily at pH >8 and additionally several racemases are known that can catalyze this process [85, 88]. This means that the hydrolysis of hydantoins is always a dynamic kinetic resolution with yields of up to 100% (Scheme 6.25). Since most hydantoinases are D-selective the industrial application has so far concentrated on D-amino acids. Since 1995 Kaneka Corporation has produced 2000 tons/year of D-p-hydroxyphenylglycine with a D-hydantoinase, a d-carbamoylase [87] and a base-catalysed racemisation [85, 89]. 

The available data suggest that in aqueous solution and at neutral pH prolyl isomerization proceeds according to a simple, one-step mechanism. Solvent water does not participate in the reaction and there is no accumulation of intermediates. The energy barrier to isomerization is enthalpic and represents the energy of resonance stabilization that is possessed by the C—N imide bond. 

As indicated above, the barrier to prolyl cis—trans isomerization is the resonance stabilization energy that is possessed by the C-N imide bond. The task of a prolyl isomerase is, therefore, to develop an enzymatic-chemical strategy that will result in the lowering of this barrier. When one reflects on the strategies that might be used by an enzyme, one realizes that there are two general mechanisms catalysis by distortion and nucleophilic catalysis (see Scheme V). 

The surface chemical structure of several thin polyimide films formed by curing of polyamic acid resins was studied using X-ray photoelectron spectroscopy (ESCA or XPS). The surface modifications of one of the polymer systems after exposure to KOH, after exposure to temperature and humidity, after exposure to boiling water, and after exposure to O2 and 02/CF plasmas were also evaluated. The results showed imide bond formation for all cured polyimide systems. It was found that (a) K on the surface of the polyamic acid alters the "normal" imidization process, (b) cured polyimide surfaces are not invarient after T H and boiling water exposures, and (c) extensive modifications of cured polyimide surfaces occur after exposures to plasma environments. Very complex surfaces for these polymer films were illustrated by the C Is, 0 Is, N Is and F Is line characteristics. 

Potentiometric titration of simple proline derivatives and of poly-O-acetyl-hydroxyproline in acetic anhydride also demonstrate protonation of the imide linkages with about 0.35 mole proton boiuid per mole imide bond (Steinberg et ah, 1960o). 

Studies on host-guest peptides have shown that incorporation of a proline residue into peptides which have a high tendency to fold into ordered secondary structures disrupts the onset of helical as well as P-sheet conformations and increases solubility and coupling rates.f Based on this observation, serine- and threonine-derived oxazolidine, and cysteine-derived thiazolidine derivatives (pseudoprolines) were proposed as valuable tools for combining protection of their side-chain functions with the simultaneous solubilization of the peptide chain. Due to the induction of kink conformations in the peptide backbone, originating from the preference of these pseudoproline residues to adopt the cis-imide bond configuration, insertion of such derivatives into peptides prevents self-association and P-structure formation. 

A change in conformation must, theoretically, result from the opening of imide linkages. Such changes in structure would be analogous to phenomena involved in denaturation of enzymes. The breaking of covalent imide bonds in proteinoids, however, partly (39) distinguishes the two processes. 

This area of Ti chemistry has advanced rapidly in recent years and has been reviewed.108-110 In addition, theoretical studies have probed in detail the nature of the Ti-imide bond.111-115... 

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