Phosphorylation mechanisms in amide media (original) (raw)
Related papers
Journal of Biological Chemistry, 2013
Background: A cysteine, a glutamic acid, and a lysine are the well known amidase catalytic residues. Results: Mutating the neighboring, structurally conserved Glu-142 inactivates the enzyme, but the active site cysteine still reacts with acrylamide via its double bond. Conclusion: Glu-142 positions the amide for productive nucleophilic attack by the cysteine. Significance: An intact catalytic tetrad is required for amidase activity.
Reactions in the presence of organic phosphites, II: Low‐temperature amidatior in solvent
Journal of Polymer …, 1984
Polyamides and related model compounds were prepared from carboxy acids and primary amines by reacting them with triphenylphosphite in an appropriate solvent at 100°C. The reactions proceeded in the absence of organic base but were accelerated by the addition of bases such as pyridine. Nevertheless, even the powerful combination of '3c and 31P NMR failed to indicate the presence of pyridinium phosphite in the reaction mixture. In the reaction of a primary amine and carboxyl groups a detectable amount of the diphenoxy aminophosphine intermediate was observed. The end products are the amides, phenol, and diphenyl phosphite. When primary amine was not present a slow formation of a phenyl ester of the carboxylic acid was evident. All the intermediate species and the end products were formed with or without added pyridine. A mixed anhydride of carboxylic acid and phosphite was never seen. The results in this article are fundamentally the same as those in the companion article (I) for which the data were obtained at 280°C in the absence of solvent and base. However, because the reaction went quickly to completion at 280"C, the diphenoxy aminophosphine intermediate was not observed. A mechanism for the amidation in which the diphenoxy aminophosphine is an initial reaction intermediate is proposed. This species reacts with the carboxylic acid through an intramolecular substitution to give an amide. This mechanism may be valid for the high-temperature reactions as well. Several minor unclear points are indicated.
International Journal of Pharmaceutics, 1995
The preparation, kinetics and mechanism of degradation of four amidals (1-4), formed from the reaction of benzamide, N-methylbenzamide, nicotinamide, and N-methylnicotinamide with 3,4-dihydro-2H-pyran, are reported. The hydrolyses of the N-methyl amidals 2 and 4 were found to follow first-order kinetics. The degradation of amidal 2 was studied in detail and was catalyzed not only by specific acid catalysis, but also by a general acid catalysis; the second-order rate constant for the involvement of H3PO 4 was about 4 M-1 h-1. Amidal 3 was resistant to acid-catalyzed degradation in 0.05 M phosphate buffer at pH 3.0 and 37 ° C, whereas the phenyl analogue, 1, under similar conditions, exhibited a tl/2 value of 98.4 days. N-methylation of the carboxamide moiety in both the phenyl and pyridyl amidals (i.e., 1 and 3, respectively) had a marked accelerating effect on the rate of hydrolysis, and this was attributed to the inductive effect of the N-methyl group which stabilizes the proposed transition state in the degradation mechanism. In acid media, amidals of 3,4-dihydro-2H-pyran were found to hydrolyze much more slowly than acetals and acylals of 3,4-dihydro-2H-pyran due to the greater stability of the protonated amidal species to unimolecular C-N bond cleavage. Substitution of an N-nicotinoyl group in place of the N-benzoyl moiety in the N-methyl-3,4-tetrahydro-2H-pyran amidal 2 resulted in a much slower rate in the acid-catalyzed hydrolytic cleavage reaction. The results indicated that the amidals formed from carboxamides and 3,4-dihydro-2H-pyran undergo degradation to the parent carboxamide via an acid-catalyzed unimolecular mechanism.
Analyzing Kemp’s amide cleavage: A model for amidase enzymes
Computational and Theoretical Chemistry, 2011
a b s t r a c t DFT calculations at B3LYP/6-31G (d, p) level for the cleavage reactions in Kemp's mono-and di-acid amides 1-9 (an amidase model) under physiological conditions, indicate that the rate limiting step in the acylolysis process is a proton transfer from the carboxyl group onto the amide carbonyl oxygen. It is proposed that accelerations in rate are mainly due to the distance between the two reactive centers (r) and the attack (hydrogen bond) angle (a). In fact, a linear correlation was found between the activation energy (DG à ) and r 2 Â sin (180 À a). On the other hand, in contrast to previous studies the ground-state pseudoallylic strain effect was found to contribute a little if any to the cleavage rate in Kemp's triacid tertiary amides. In addition, the calculation results suggest a change in the mode and the mechanism of the amide cleavage upon changing the pH of the reaction medium. Thus, peptidase enzymes are extremely reactive around neutral pH while their activities vanish under basic medium.
Tetrahedron, 2001
AbstractÐThe rate dependence on both the acidity and the temperature of the hydrolysis of N-(methoxyprop-2-yl)benzanilide (1), assisted by vicinal amide function, was investigated and the thermodynamic activation parameters were calculated. The rate constant of the ®rst step of the overall process increases when the acidity is raised, while the second step is slowed down. The negative value of DS ± (2100.9 J mol 21 K 21 ) measured for the second step suggests the participation of water in the transition state. q
Journal of Polymer Science: Polymer Chemistry Edition, 1984
When reacted for periods of 5-10 min at temperatures of about 280400°C in the presence of certain organic phosphites polymers that contain available carboxy and aliphatic amine groups undergo amidation. This reaction can increase the molecular weight of many aliphatic polyamides by their self-reaction in an extruder. Block or graft copolymers can be formed by reacting polymers that contain aliphatic amines with others that contain carboxyl. Studies of model compounds in the companion article (11) indicate that polymerization proceeds through an diaryloxy or dialkoxy amino phosphine intermediate to produce amide bonds and disubstituted phosphite reaction by-products. In the absence of primary amines in the reaction mixture an ester is slowly formed from the carboxyl end group of the polymer and the oxysubstituent of the phosphite. In no case was a phosphoruscontaining mixed anhydride detected. The mechanistic identity of the low temperature reactions in article I1 and the high temperature reactions in this article has not been proved conclusively, however.
Neighboring amide group participation in ester aminolysis in aprotic solvents
The piperidinolysis of 8-quinolyl-, p-nitrophenyl-, o-, and p-piperidinocarbonylphenyl acetates in acetonitrile and in chlorobenzene was studied at 25°C. The strictly second order kinetic behaviour and the weaks solvent-dependence of the rate of the reaction of o-piperidinocarbonylphenyl acetate indicate anchimeric assistance by the o-amide group, and support the suggestion that amide groups of hydrophobic enzyme active sites may act as general base catalysts.
Amide Activation in Ground and Excited States
Molecules
Not all amide bonds are created equally. The purpose of the present paper is the reinterpretation of the amide group by means of two concepts: amidicity and carbonylicity. These concepts are meant to provide a new viewpoint in defining the stability and reactivity of amides. With the help of simple quantum-chemical calculations, practicing chemists can easily predict the outcome of a desired process. The main benefit of the concepts is their simplicity. They provide intuitive, but quasi-thermodynamic data, making them a practical rule of thumb for routine use. In the current paper we demonstrate the performance of our methods to describe the chemical character of an amide bond strength and the way of its activation methods. Examples include transamidation, acyl transfer and amide reductions. Also, the method is highly capable for simple interpretation of mechanisms for biological processes, such as protein splicing and drug mechanisms. Finally, we demonstrate how these methods can p...
Biotechnology and Applied Biochemistry, 2001
Peptide amidase-catalysed amidations of the Cterminal carboxylic group of peptides were studied using model substrates of a large series of N α -protected di-, tri-, tetra-and penta-peptides in the presence of NH 4 HCO 3 as the ammonium source. The maximal yields of amide syntheses were achieved in a medium consisting of acetonitrile with 20-25 vol % of dimethylformamide and 3 vol % of water. Under these conditions, the substrate specificity of the enzyme was more restricted in the synthetic reaction than was found for the amide hydrolysis. Elongation of the peptide chain had a negative effect on enzymic amidation. Thus the direct amidation of N α -t-butoxycarbonyl-protected Leu-enkephalin resulted in a low yield of protected enkephalin amide.