Glycinamide hydrolysis

The amide and peptide linkages are much more difficult to hydrolyze than the ester grouping. Both free and metal bound groups hydrolyze with second-order rate constants approximately 10 -10 less than for the corresponding esters. There are two potential sites for coordination in the -CONHR residue, namely at the carbonyl O in 13 and at the amide N in 14 where ionization of the amide proton is induced (Sec. 6.4.3). Cu + promotes hydrolysis of glycinamide at low pH where it is present as 13. However it inhibits hydrolysis at high pH, where it is 14, to such a degree that hydrolysis cannot be observed. ... 

Copper(JI) has been found to inhibit the hydrolysis of glycylglycine in basic solution (pH> 11).127 Conley and Martin128 have also found that, at pH values in excess of 11, copper(II) inhibits the hydrolysis of glycinamide due to amide hydrogen ionization. Similar results were obtained with picolinamide, and a bis-picolinamide complex of nickel(II) containing deprotonated amide groups was isolated.128... 

In the case of amino acid ester and amide complexes, the intramolecular hydrolysis reaction was not observed directly, but was deduced from the results of lsO tracer studies. However, recently the cis-hydroxo and cis-aqua complexes derived from the bis(ethylenediamine)cobalt(III) system, containing glycinamide, glycylglycine and isopropylglycylglycinate, have been isolated and their subsequent cyclization studied over the pH range 0-14.160,161... 

Recent work150 also clarifies a previous report on the hydrolysis of cis-[Co(en)2Br(GlyNH2)]2+. In the initial study157 it was concluded that the hydroxo glycinamide ion reacted rapidly under the conditions of base hydrolysis and the subsequent process observed spectrophotometrically... 

Early work" established that Cu", Ni" and Co" promote the hydrolysis of glycinamide in the pH range 9.35 to 10.35 at temperatures of 6.5 to 75 °C. Bamann and his collaborators carried out an extensive series of studies on the metal ion-promoted hydrolysis of peptides and related compounds" and a review of this early work is available." Highly charged ions such as thorium(IV) were found to promote the hydrolysis of leucylglycylglycine at pH values as low as 5. The thorium(IV) species is very extensively hydrolyzed at this pH and the reaction is presumably heterogeneous. Gel hydrolysis is effective at relatively low temperatures (37 °C), whereas observable effects were only obtained with such ions as copper(II) at temperatures of ca. 70 °C. 

Dioeotide Formation. Figure 2 presents the time course of the dipeptide formation reaction. The limiting reactant, Z-Tyr-OMe, is depleted rapidly, being converted via nucleophilic attack of the glycinamide to the desired dipeptide product, Z-Tyr-Gly-NH2 via trans-esterification to a transient intermediate, Z-Tyr-OHx and via hydrolysis to the undesired side product Z-Tyr-OH. Dipeptide yield, based on the more expensive amino acid substrate, Z-Tyr-OMe, is 75% after 30 minutes using an enzyme concentration of 1 /iM, Both the... 

The hydrolysis of glycinamide is catalyzed by [Co(ethylenediamine)2]. Propose a mechanism for this reaction. 

The hydrolysis of glycinamide complexes of cobalt(m), viz. cis-[Co(en)2Br(glyNR R )] to give [Co(en)2(gly)] +, has been studied in alkaline solution by kinetic, stereochemical, and 0-labelling methods. The bromide ion is displaced first, and then comes cobalt-promoted hydrolysis... 

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