A mechanism for efficient proton-transfer catalysis. Intramolecular general acid catalysis of the hydrolysis of 1-arylethyl ethers of salicylic acid

1999 ◽  
Vol 77 (5-6) ◽  
pp. 792-801 ◽  
Author(s):  
Sarah E Barber ◽  
Kathryn ES Dean ◽  
Anthony J Kirby
Keyword(s):  
Hydrogen Bond ◽  
Salicylic Acid ◽  
Proton Transfer ◽  
Acid Catalysis ◽  
Enzyme Mechanism ◽  
Base Catalysis ◽  
Strong Hydrogen Bond ◽  
Cooh Group ◽  
Tert Butyl ◽  
General Acid

The tert-butyl (1) and 1-arylethyl ethers (2) of salicylic acid are hydrolyzed with efficient general acid catalysis by the ortho-COOH group. The half-life of the neutral COOH form of the tert-butyl ether is 15.2 min at 39°, and the estimated acceleration by the COOH group of 2, X = Me, Y = H is 2.13 × 105. The salicylate leaving group from 2 (X = Me, Y = H) has an effective pKa of 2.9, compared with a nominal pKa of 8.52. Analysis of substituent effects in both arylethyl and leaving groups provides the most detailed available mechanistic insight into a reaction involving efficient intramolecular proton-transfer catalysis. The mechanism is very different from classical general acid-base catalysis. Proton transfer takes place very rapidly within a developing strong hydrogen bond, and though an integral part of the C—O cleavage process is practically uncoupled from it. "Strategic delay" of the proton-transfer step, relative to C—O cleavage, makes a significant contribution to efficiency by setting up the conditions for the formation of the strong, intramolecular hydrogen bond.Key words: catalysis, carboxyl, hydrogen bond, proton transfer, enzyme mechanism.

Deuterium exchange of C-methyl protons in lumazine derivatives

1970 ◽  
Vol 48 (2) ◽  
pp. 263-270 ◽  
Author(s):  
J. M. McAndless ◽  
Ross Stewart
Keyword(s):  
Proton Magnetic Resonance ◽  
Proton Magnetic Resonance Spectroscopy ◽  
Acid Catalysis ◽  
Deuterium Exchange ◽  
Base Catalysis ◽  
Resonance Spectroscopy ◽  
Methyl Group ◽  
General Base ◽  
General Acid ◽  
Acid Catalyzed

Proton magnetic resonance spectroscopy has been used to examine the deuterium exchange of the methyl protons in two lumazine derivatives. The exchange occurs at the C-7 methyl group in 6,7,8-trimethyllumazine (2) and at the C-6 methyl group in 1,7-dihydro-6,7,8-trimethyllumazine (3). The former reaction is subject to both general acid- and general base-catalysis but the latter only to general acid-catalysis. Plausible mechanisms for the reactions of both compounds are advanced, involving in the case of 3, acid-catalyzed addition of water across the C6—N5 double bond.

Complexes of N-methylxanthines with carboxylic acids

1968 ◽  
Vol 46 (19) ◽  
pp. 3055-3059 ◽  
Author(s):  
Denys Cook ◽  
Zephyr R. Regnier
Keyword(s):  
Hydrogen Bond ◽  
Acetic Acid ◽  
Salicylic Acid ◽  
Infrared Spectroscopy ◽  
Nitrogen Atom ◽  
Imidazole Ring ◽  
Intermolecular Forces ◽  
Strong Hydrogen Bond ◽  
Lipid Solubility ◽  
Aromatic Acids

Complexes of caffeine and theobromine, with acetic and salicylic acid, have been studied by means of infrared spectroscopy. In the complexes with aromatic acids a fairly strong hydrogen bond exists between the carboxylic OH group and the nitrogen atom N-9 in the imidazole ring. The acetic acid complexes involve no strong intermolecular forces and are probably weak lattice complexes.The complexes with aromatic acids are discussed in relation to theories of lipid solubility and gastrointestinal absorption.

scholarly journals pH-dependence and structure–activity relationships in the papain-catalysed hydrolysis of anilides

1971 ◽  
Vol 124 (1) ◽  
pp. 117-122 ◽  
Author(s):  
G. Lowe ◽  
Y. Yuthavong
Keyword(s):  
Acid Catalysis ◽  
Ph Dependence ◽  
Base Catalysis ◽  
General Base ◽  
Structure Activity ◽  
Equilibrium Binding ◽  
General Acid ◽  
Leaving Group ◽  
Hydrolysis Of ◽  
Equilibrium Binding Constant

The pH-dependence of the Michaelis–Menten parameters for the papain-catalysed hydrolysis of N-acetyl-l-phenylalanylglycine p-nitroanilide was determined. The equilibrium binding constant, Ks, is independent of pH between 3.7 and 9.3, whereas the acylation constant, k+2, shows bell-shaped pH-dependence with apparent pKa values of 4.2 and 8.2. The effect of substituents in the leaving group on the acylation constant of the papain-catalysed hydrolysis of hippuryl anilides and N-acetyl-l-phenylalanylglycine anilides gives rise in both series to a Hammett ρ value of -1.04. This indicates that the enzyme provides electrophilic, probably general-acid, catalysis, as well as the nucleophilic or general-base catalysis previously found. A mechanism involving a tetrahedral intermediate whose formation is general-base-catalysed and whose breakdown is general-acid-catalysed seems most likely. The similarity of the Hammett ρ values appears to exclude facilitated proton transfer as a means through which the specificity of papain is expressed.

Kinetics and mechanism of solvolysis of N-aryl sulfuric diamides

1990 ◽  
Vol 55 (1) ◽  
pp. 202-222 ◽  
Author(s):  
Jaromír Kaválek ◽  
Ulrika Králíková ◽  
Vladimír Macháček ◽  
Miloš Sedlák ◽  
Vojeslav Štěrba
Keyword(s):  
Acid Catalysis ◽  
Catalytic Effect ◽  
Kinetics And Mechanism ◽  
Base Catalysis ◽  
Reactive Intermediate ◽  
Hydrolysis Kinetics ◽  
General Acid ◽  
Acid And Base ◽  
Elimination Mechanism ◽  
Acid And Base Catalysis

The methanolysis and hydrolysis kinetics have been studied with the following sulfuric diamide derivatives: N-methyl-N-phenyl- (IIIa), N-methyl-N-(4-methoxycarbonylphenyl)- (IIIb), N-(4-methoxycarbonylphenyl)- (IIIc), N-methyl-N-(2-methoxycarbonylphenyl)- (IIId), N-(2-methoxycarbonylphenyl)- (IIIe), and N-methyl-N-(2,4-dibromophenyl)- (IIIf). The solvolyses of the neutral substrates IIIa and IIIb proceed by the addition-elimination mechanism. In the presence of the solvent lyate ions the solvolyses go by the E1cb mechanism. The solvolyses of the conjugated bases of compounds IIIa and IIIb are subject to general acid catalysis, the effects of the ring substituents being opposite to those in the addition-elimination mechanism. The solvolyses of compounds IIId and IIIf exhibit a distinct catalytic effect of neighbouring group; the reaction goes via a reactive intermediate, the transformation of the intermediate into the solvolysis product being subject to general acid and base catalysis.

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