Deuterium Oxide Solvent Isotope Effect Research Articles

Reaction of imidazole with toluene-4-sulfonate salts of substituted phenyl N-methylpyridinium-4-carboxylate esters: special base catalysis by imidazole.

The reaction of imidazole in aqueous solution with toluene-4-sulfonate salts of substituted phenyl N-methylpyridinium-4-carboxylate esters obeys the rate law: k(obs) - k(background) = k2[Im] + k3[Im]2 where [Im] is the imidazole concentration present as free base. The parameters k2 and k3 fit Brønsted type free energy correlations against the pKa of the leaving phenol with betaLg values of -0.65 and -0.42 respectively. The imidazolysis is insensitive to catalysis by general bases and yet k3 for the 3-cyanophenyl ester possesses a deuterium oxide solvent isotope effect of 4.43 consistent with rate limiting proton transfer. A special catalytic function is proposed for decomposition of the tetrahedral addition intermediate (T+/-) via k3 whereby the catalytic imidazole interacts electrophilically with the leaving phenolate ion and removes a proton from the nitrogen in the rate limiting step with subsequent non-rate limiting ArO-C bond fission. This is consistent with the change in effective charge on the leaving oxygen in the transition structure of k3 which is more positive (-0.42) than that expected (-0.60) for the equilibrium formation of the zwitterion intermediate. The catalytic function at the leaving oxygen is likely to be an electrophilic role of the NH as a hydrogen bond donor. In the k2 step the deuterium oxide solvent isotope effect of 1.51 for the 3-cyanophenyl ester and the betaLg of -0.65 are consistent with rate limiting expulsion of the phenolate ion from the T+/- intermediate. The absence of general base catalysis of imidazolysis rules out the established mechanism for aminolysis of esters where T+/- is stabilised by a standard rate limiting proton transfer. The kinetically equivalent term for k3 where T- reacts with the imidazolium ion as an acid catalyst would require this step to be rate limiting and involve proton transfer not consistent with departure of the good aryl oxide leaving group.

Carboxyl group participation in sulfate and sulfamate group transfer reactions

The pH dependence for the hydrolysis of N-(2-carboxyphenyl)sulfamic acid exhibits a plateau region corresponding to participation of the carboxyl function. A normal deuterium oxide solvent isotope effect indicates that proton transfer from the carboxylic acid is concerted with sulfamate group transfer to water. Hydrolysis of salicylic sulfate and N-(2-carboxyphenyl)sulfamate in /sup 18/O-enriched water yields salicylic acid and anthranilic acids with no enrichment, excluding catalysis by neighboring nucleophilic attack on sulfur by the carboxylate group. Intermolecular catalysis by carboxylic acids is demonstrated in the hydrolysis of N-(1-naphthyl)sulfamic acid; the mechanism is shown to involve preequilibrium protonation of the nitrogen followed by nucleophilic attack on sulfur by the carboxylate anion. Fast decomposition of the acyl sulfate completes the hydrolysis; this mechanism is considered to be the most efficient but is excluded in the intramolecular case which is constrained by the electronic requirements of displacement at the sulfur atom (6-ENDO-tet).

Direct spectrophotometric observation of an O-acylisourea intermediate: concerted general acid catalysis in the reaction of acetate ion with a water-soluble carbodi-imide

The rate constants for formation and decay of O-acylureas from carbodi-imide and acids have been measured using aqueous media. The O-acetylisourea from acetate and N-ethyl-N′-(3-trimethylammoniopropyl)carbodi-imide (ETC) possesses an acidic group of pK 6.8 and decomposes (k2) in its acid form as the dication by reaction with acetate ion or water. The reaction of the carboxylate anion with ETC is general acid catalysed (k1=ΣkHA[RCO2–][HA]) and the deuterium oxide solvent isotope effect indicates a rate-limiting proton transfer except for the oxonium ion acting as acid. The Brønsted α value for variation of the structure of HA (0.67) is consistent with a proton transfer concerted with nucleophilic attack by the acetate anion. A concerted mechanism is consistent with the weak basicity of the carbodiimide and the weak acidity of the isourea adduct. The third-order term involving acetic acid, acetate ion, and carbodi-imide carries ca. 60% of the total reaction flux at pH 6.80 and 1 M total acetic acid buffer concentration. At this pH ca. 40% of the reaction flux goes through the stepwise ‘Khorana’ mechanism with specific acid catalysis. Intramolecular general acid catalysis is demonstrated to occur in the reaction of 2,2-diethylmalonic acid monoanion with ETC and the effective molarity compared with intermolecular catalysis is 15M. Attack of carboxylate anions on ETC with N-chloroethylmorpholinium ion as the general acid has a Brønsted type βNof 0.46.

Stepwise proton transfer in the acid-catalysed hydrolysis of 3,1-benzoxazin-4-ones: electrostatic or hydrogen-bond stabilisation of the conjugate acid

The hydrolysis of 3,1-benzoxazin-4-ones is catalysed by buffer acids and by intramolecular carboxylic acid groups suitably placed on the heterocyclic nucleus. Small or inverse deuterium oxide solvent isotope effects on the acid catalytic terms are consistent with both inter- and intra-molecular acid catalyses proceeding through a pre-equilibrium protonation mechanism. Proton transfer to the N-1 position concerted with attack at C-2 is not expected because the N-1 protonated 3,1-benzoxazin-4-one is a relatively stable species. The function of the 8-carboxy-anion in the catalysed ring hydrolysis of 8-carboxy-3,1-benzoxazin-4-one is to stabilise the protonated nitrogen (N-1) by electrostatic or hydrogen-bonding interaction.

Pressure effects on aminonaphthalene dye fluorescence in H2O and D2O

The pressure dependence of excited-state proton transfer equilibria has been examined for aqueous solutions of several substituted napthalene dyes, in particular 1-dimethylaminonaphthalene-5-sulfonic acid (DANS). The pressure-induced shift in equilibrium is characterized by volume changes spanning the range ΔV*=−18 cm3 mole−1 to ΔV*=+4 cm3-mole−1. A deuterium oxide solvent isotope effect is evident in the pressure response of DANS, leading to a 35% smaller ⋎ΔV*⋎ in D2O relative to H2O.

Reaction of amines and oxygen nucleophiles with 5-nitrocoumaran-2-one: nucleophilic and general base catalysis of hydrolysis

The reaction of nitrocoumaranone (1) with bases was studied using aqueous solution. Primary and secondary amines react to yield the 2-hydroxy-5-nitrophenylacetamide. A negligible deuterium oxide solvent isotope effect and a large Bronsted βn confirm the nucleophilic pathway and a class II aminolysis. Carboxylic acids, phosphate, and heterocyclic amines yield the acid product, and the low Bronsted β, deuterium oxide solvent isotope effect of 2–3, and comparison with reactivity against 4-nitrophenyl acetate indicate a general-base catalysed path. Tertiary alkylamines (yielding acid) are more efficient than predicted from the general base Bronsted relationship, are less efficient than the primary amines of similar pKa, and have negligible deuterium oxide solvent isotope effect; these data and comparison with 4-nitrophenyl acetate reactivity indicate a nucleophilic mechanism.Consideration of frontier orbitals and stereoelectronic factors indicates that the E1cB mechanism is an ‘allowed’ process which must be suppressed by the efficiency of trapping of the keten intermediate by the neighbouring hydroxy function.

Effects of substituents on the hydrolysis of 4-nitrophenyl acetate catalysed by 2-substituted imidazoles

The hydrolysis of 4-nitrophenyl acetate catalysed by a series of 2-substituted imidazoles has been studied in water at 30°. The substituents used are the alkyl groups Me, Et, Pri, and But, and a few hydroxyalkyl groups. Activation parameters and the deuterium oxide solvent isotope effect have been determined for some of these imidazoles. In creased bulkiness of the 2-substituents results in decreased rates for the nucleophilic catalysis observed for most of the imidazoles studied. The results are analysed in terms of the Bronsted catalysis law assuming a common slope of 0.80 and an equal pKa of 7.80, giving an extrapolated rate value to each imidazole. Based on the analysis, a measure of the steric effect of the individual imidazole relative to the parent compound is estimated. The mechanism by which 2-(1,1-dimethyl-2-hydroxyethyl)imidazole acts for the hydrolysis is judged as a partial general base catalysis.

Cycloamylose-accelerated cleavage of acylimidazoles

Hydrolyses of N-trans-cinnamoylimidazole ( 1) and N-acetylimidazole ( 2) were accelerated by cyclohexaamylose (α-CA) and cycloheptaamylose (β-CA) at 25°C. The cleavage of the amide bond in 1 at pH 9.0 was accelerated by α-CA and β-CA by 28- and 38-fold, respectively, whereas the cleavage of the amide bond in 2 at pH 7.0 was accelerated by α-CA and β-CA by 50- and 28-fold, respectively. The β-CA-accelerated hydrolysis of 1 proceeded via binding, acylation of β-CA, and deacylation of β-CA trans-cinnamate, which is consistent with the pathway used by serine proteases. The deuterium oxide solvent isotope effects for acylation and deacylation steps indicate nucleophilic attack in acylation and general basic attack in deacylation. The present finding of the acceleration by cycloamyloses in the cleavages of amide bonds in 1 and 2 indicates that cycloamyloses are an excellent model for hydrolytic enzymes.

Intramolecular general base-catalyzed ester hydrolyses by the imidazolyl group.

Intramolecular general base catalysis by the imidazolyl group was found in the hydrolyses of endo-5-[4;(5')-imidazolyl]-bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate and endo-5-[4'(5')-imidazolyl]bicyclo[2.2.2]oct-endo-2-yl trans-cinnamate in which the imidazolyl and trans-cinnamoyl groups are bound in close proximity to each other by rigid bicyclic rings. The rate constants for the intramolecular general base-catalyzed hydrolyses at 60 degrees are 6.4 X 10(-7) sec-1 for the former and 1.8 X 10(-7) sec-1 for the latter and the deuterium oxide solvent isotope effects are 3.0 for both. On the other hand, no intramolecular catalytic participation of the imidazolyl group was observed in the hydrolyses of the endo-exo isomers, exo- 5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate and endo-5[4'(5')-imidazolyl]bicyclo[2.2.2]oct-exo-2-yl trans-cinnamate, in which the imidazolyl groups are located far from the trans-cinnamoyl groups. Intramolecular general base-catalyzed hydrolyses by the imidazolyl groups in endo-5[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate and endo-5-[4'(5')-imidazolyl]bicyclo[2.2.2]oct-endo-2-yl trans-cinnamate can serve as models of serine esterase-catalyzed hydrolyses.

Catalysis of ester hydrolysis by N-(2-dimethylaminoethyl)acetohydroxamic acid ( I)

N-(2-dimethylaminoethyl)acetohydroxamic acid was synthesized. This compound, which incorporates a dimethylamino group as a second functionality into the hydroxamic acid molecule, catalyzes the hydrolysis of p-nitrophenyl acetate faster than acetohydroxamic acid itself does. The function of the dimethylamino group is to labilize the intermediate formed in the reaction, thus assisting deacylation intramolecularly. The dimethylamino group carries out this function by intramolecular general base catalysis. Nucleophilic catalysis is ruled out by the sizable deuterium oxide solvent isotope effect ( k H 2O k D 2O = 2.05 ) found. General acid-hydroxide ion catalysis is ruled out by determination of the lack of reaction with azide ion, which does not possess a dissociable proton, with the intermediate in this reaction. The deuterium oxide solvent isotope effect on the azide ion reaction of the intermediate also rules out a general acid-hydroxide ion reaction.

Location of deuterium oxide solvent isotope effects in the glutamate dehydrogenase reaction.

Stopped flow studies of D2O kinetic solvent isotope effects on the reaction catalyzed by L-glutamate dehydrogenase reveal, in addition to several effects apparently attributable simply to pKa shifts, a 2-fold pH-independent effect on the velocity of the steady state oxidative deamination of L-glutamate by enzyme and NADP. Comparable pH-independent D2O kinetic solvent isotope effects are seen both in a transient phase of the reaction in which alpha-ketoglutarate is displaced by L-glutamate from an enzyme-NADPH-alpha-ketoglutarate (product) complex and in an analogous model reaction in which alpha-ketoglutarate is displaced by D-glutamate. These results suggest that alpha-ketoglutarate dissociation from an enzyme-NADPH-alpha-ketoglutarate complex is rate-limiting in the steady state.

Hydrolysis of phosphinic esters: general-base catalysis by imidazole

Imidazole catalyses the hydrolysis of aryl diphenylphosphinates (I). At 25° the Hammett-σ-ρ value for the bimolecular rate constant (kim) is 2·88 and at 55° is 2·64; hydroxide-ion catalysis (kOH) at 25° has a smaller ρ value 1·55. Ratio of phosphate dianion catalysis (kHPO4=) to kim is ca. 5 for 4-nitrophenyl diphenylphosphinate; the deuterium oxide solvent isotope effect on kim is 2·15 and no departure from 1:1 stoicheiometry was observed in the imidazole-catalysed hydrolysis of the 4-nitrophenyl ester. These results indicate that imidazole acts as a general-base catalyst. Nucleophilic catalysis is observed with imidazole-catalysed hydrolysis of 4-nitrophenyl dimethyl-phosphate, diphenylphosphate and di-4-nitrophenylphosphate (kimH/kimD= 1·03, 1·02, 1·53 respectively). Steric crowding of the transition state renders nucleophilic catalysis inefficient for the diphenylphosphinate esters.A diagnostic tool not previously employed to distinguish general-base from nucleophilic catalysis by imidazole is discussed. The good Hammett-σ plot for imidazole catalysis in diphenylphosphinate ester hydrolysis argues for a general-base mechanism and for a stepwise rather than a concerted displacement.

Deuterium oxide solvent isotope effects on nitrogen-hydrogen oxygen, oxygen-hydrogen...nitrogen, and nitrogen-hydrogen...nitrogen intramolecular hydrogen bonds

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDeuterium oxide solvent isotope effects on nitrogen-hydrogen oxygen, oxygen-hydrogen...nitrogen, and nitrogen-hydrogen...nitrogen intramolecular hydrogen bondsJohn L. Haslam and Edward M. EyringCite this: J. Phys. Chem. 1967, 71, 13, 4470–4475Publication Date (Print):December 1, 1967Publication History Published online1 May 2002Published inissue 1 December 1967https://doi.org/10.1021/j100872a049RIGHTS & PERMISSIONSArticle Views129Altmetric-Citations22LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (601 KB) Get e-Alerts