Attack Of Hydroxyl Ion Research Articles

A kinetic study of the basic hydrolysis of 2-phenylethyl nitrite in the presence of borate buffer and β-cyclodextrin

The kinetics of the hydrolysis of 2-phenylethyl nitrite have been studied in basic aqueous solutions (borate buffer) in the absence and presence of β-cyclodextrin. The observed kinetic trends show that the hydrolysis reaction consists of at least three subsequent processes. The first is a fast acid-base reaction between the boron atom of boric acid and oxygen atom of the alkyl nitrite. The second one should be the nucleophilic attack of hydroxyl ion on the alkyl nitrite. The last process could be referred to as a combination of transfer of hydrogen acid to a water molecule followed by ruptures of nitrogen-oxygen and boron-oxygen bonds. The effect of β- cyclodextrin on each process is also discussed.

Anaerobic chlorophyll isocyclic ring formation in Rhodobacter capsulatus requires a cobalamin cofactor.

The isocyclic ring of bacteriochlorophyll (BChl) is formed by the conversion of Mg-protoporphyrin monomethyl ester (MPE) to protochlorophyllide (PChlide). Similarities revealed by blast searches with the putative anaerobic MPE-cyclase BchE suggested to us that this protein also uses a cobalamin cofactor. We found that vitamin B(12) (B(12))-requiring mutants of the bluE and bluB genes of Rhodobacter capsulatus, grown without B(12), accumulated Mg-porphyrins. Laser desorption/ionization time-of-flight (LDI-TOF) MS and NMR spectroscopy identified them as MPE and its 3-vinyl-8-ethyl (mvMPE) derivative. An in vivo assay was devised for the cyclase converting MPE to PChlide. Cyclase activity in the B(12)-dependent mutants required B(12) but not protein synthesis. The following reaction mechanism is proposed for this MPE-cyclase reaction. Adenosylcobalamin forms the adenosyl radical, which leads to withdrawal of a hydrogen atom and formation of the benzylic-type 13(1)-radical of MPE. Withdrawal of an electron gives the 13(1)-cation of MPE. Hydroxyl ion attack on the cation gives 13(1)-hydroxy-MPE. Withdrawal of three hydrogen atoms leads successively to 13(1)-keto-MPE, its 13(2)-radical, and cyclization to PChlide.

Factors Governing the Enhanced Reactivity of Five-Membered Cyclic Phosphate Esters

Ab initio calculations and continuum dielectric methods have been employed to map out the lowest activation free-energy profiles for the alkaline hydrolysis of a five-membered cyclic phosphate, methyl ethylene phosphate (MEP), its acyclic analog, trimethyl phosphate (TMP), and its six-membered ring counterpart, methyl propylene phosphate (MPP). The rate-limiting step for the three reactions was found to be hydroxyl ion attack at the phosphorus atom of the triester. By performing constrained optimization along the reaction coordinate, defined as the phosphorus to incoming hydroxyl oxygen distance, and computing the solvation free energies of the resulting stationary points, the rate-limiting transition states have been relocated in solution. Dihedral ring constraints in the five-membered ring leading to a more solvent-exposed hydroxyl group and, thus, better solvation of the cyclic transition state compared to its acyclic counter-part was found to be the dominant factor governing the rate enhancement of cyclic MEP relative to acyclic TMP alkaline hydrolysis. However, both ground-state destabilization of MEP relative to MPP, due to ring strain, and transition-state stabilization of the five-membered cyclic phosphate transition state relative to its six-membered ring analog, due to the differential location of the transition states in solution, were found to contribute to the enhanced rates of alkaline hydrolysis of five-membered ring MEP compared to six-membered ring MPP.

Alkaline hydrolysis of cephaloridine: An 1HNMR study. Temperature dependence of the rate constants

AbstractA kinetic study on the basic hydrolysis of cephaloridine at pD= 10.5 was carried out by using the 1HNMR technique. Epimerization at H7, a nucleophilic attack of hydroxyl ion on the β‐lactam carbonyl group followed by the release of the pyridine molecule, and isomerization of the double bond at position 3 in the dihydrothiazine ring were the major reactions observed.Based on the results obtained, it should be emphasized that the presence of a pyridine group at 3′ results in a slightly increased formation constant for the exo methylene compound relative to other cephalosporins with different substituents at that position.The activation energy for the epimerization constant and the cleavage of the β‐lactam ring at pD 10.5 was 21.2 kcal/mol. © 1993 John Wiley & Sons, Inc.

Concerted hydroxyl ion attack and pseudorotation in the base-catalyzed hydrolysis of methyl ethylene phosphate

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConcerted hydroxyl ion attack and pseudorotation in the base-catalyzed hydrolysis of methyl ethylene phosphateCarmay Lim and Philip ToleCite this: J. Phys. Chem. 1992, 96, 13, 5217–5219Publication Date (Print):June 1, 1992Publication History Published online1 May 2002Published inissue 1 June 1992https://doi.org/10.1021/j100192a007RIGHTS & PERMISSIONSArticle Views102Altmetric-Citations29LEARN 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 (357 KB) Get e-Alerts

Evidence for leukotriene A 4 as an intermediate in the conversion of 5-HPETE to leukotriene B 4 catalyzed by cytochrome P-450

Hydrolysis of 5-hydroperoxyeicosatetraenoic acid catalyzed by cytochrome P-450 in the absence of NADPH formed a product with spectral and HPLC characteristics identical with those of leukotriene B4, 5(S),12(R)-dihydroxy-6-cis,8,10-trans,14-cis-eicosatetraenoic acid (LTB4). The product mixture suggests that trans-5,6-oxido-7,9-trans,11,14-cis-eicosatetraenoic acid, leukotriene A4 (LTA4) is an intermediate in the reaction. We suggest that the formation of LTB4 with the essential 6-cis stereochemistry is due to tight binding of the 5-HPETE to the cytochrome P-450 at a site that does not allow it to isomerize to the kinetically favored 6,8,10-trans configuration during attack of hydroxyl ion at C-12.

Prediction of Stability in Pharmaceutical Preparations XX: Stability Evaluation and Bioanalysis of Cocaine and Benzoylecgonine by High-Performance Liquid Chromatography

□ Specific, sensitive, reverse-phase high-performance liquid chromatographic (HPLC) assays of cocaine (I) and its hydrolysis products, benzoylecgonine (II) and benzoic acid (ΙII), have been devised with analytical sensitivities as low as 15ng/ml of plasma for I using spectrophotometric detection at 232nm. Cocaine can be separated from its hydrolysis products by extraction at pH7.5 with haloalkanes. Benzoylecgonine and benzoic acid can be extracted at pH3.0 with 1-butanol. The evaporated residues were reconstituted in acetonitrile-water for HPLC assay. The assay was used to determine the stabilities of I and II in aqueous solutions, to establish log k–pH profiles at various temperatures, and to evaluate Arrhenius’ parameters. Hydrolyses were by specific acid–base catalysis. Cocaine showed hydrogen and hydroxyl ion attack on protonated I with 40 and 90% proceeding through the benzoylecgonine route, respectively, as well as hydroxyl ion attack on neutral cocaine, with only 6% proceeding through the benzoylecgonine route. Cocaine is relatively unstable in the neutral pH range with a half-life of 5hr in buffer at pH7.25 and 40°. Similar half-lives were observed in fresh dog plasma at 300 and 30μg/ml, although one study at 0.5μg/ml indicated a doubling of the rate.

Characterisation of the imidazole ring-opened forms of trans-8,9-dihydro-8,9-dihydro-8-(7-guanyl)9-hydroxy aflatoxin B1.

Hydroxyl ion attack on aflatoxin B 1 (AFB 1 )-adducted DNA followed by acid hydrolysis releases two AFB 1 derivatives, 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl formamido) 9-hydroxy AFB 1 (major compound) and 8, 9-dihydro-8-(2-ammino-6-formamido-4-oxo-3,4dihydropyrimid-5-yl amino)9-hydroxy AFB 1 . The minor compound converts into the major isomer in aqueous dimethylsulphoxide.

Kinetics of Solvolyses of Various N, N'-Dialkyl-N-nitrosoureas in Neutral and Alkaline Solutions

a) The neutral and alkaline solvolyses of N-methyl-N'-p-fluorophenyl-N-nitrosourea, 1, 6-dimethyl-1, 6-dinitrosobiurea, N-methyl-N'-phenethyl-N-nitrosourea, trimethylenebis-N-methyl-N-nitrosourea and N, N'-dimethyl-N-nitrosourea are subject to spontaneous and specific hydroxide ion catalysis, i.e. kapp(sec-1=k0+kOH[OH-]. The decreasing order of reactivity is in the order given and is consistent with the fact that electron-with-drawing substituents abet hydroxyl ion attack by inducing a more positive center. The fact that substitution of an alkyl for a hydrogen on the N'-nitrogen inhibits hydrolysis favors the adjacent carbonyl carbon as the primary focus of hydroxide ion attack. b) The log k-pH profiles of N, N'-dimethyl-N-nitrosourea and 1, 6-dimethyl-1, 6-dinitrosobiurea show a deviation in the linearity of the alkaline branch which can be attributed to a kinetic pKa' where these compounds may exist as anions at higher pH values and thus be more resistant to hydroxide ion attack. c) The gas chromatographically analyzed alcohol products of alkaline degradation of N-alkyl-N'-nitrosourease are various in several cases and thus clearly implicate a potentiallu rearranging carbonium ion intermediate in the alkaline solvolyses of these compounds. The N-n-butyl compound gives a mixture of n-butyl-alcohol in 45% yield, and secondary butyl alcohol in 24% yield for pH values greater than 7.0. The fact that the N-isobutyl compound yields t-butyl alcohol (76%), sec-butyl alcohol (22%)and isobutyl alcohol (18%) also implicates a methyl shift. The N-alkyl-and N-benzyl-compounds yield only the corresponding alcohols.

Investigations of Hydrolytic Products of Butalbital

Two pathways of cleavage of butalbital (5-allyl-5-isobutylbarbituric acid) were elucidated. Depending upon the reaction conditions, one or both routes might be operative. These proceed initially: (a) through 1,6-ring opening to the malonuric acid, and (b) via 1,2-cleavage of the barbiturate producing the diamide. Several intermediates were isolated and identified or characterized. At pH values around neutrality and a few units above, the hydrolysis takes place solely by means of the 1,6-solvolysis; at higher alkalinities (pH about 9.5), the 1,2-ring opening plays a role. Kinetics of acylureide breakdown at several hydrogen-ion concentrations and temperatures were studied. Data for the diamide and malonuric acid are reported. Ionic strength effects on the alkaline solvolysis of butalbital were examined. A positive relationship of the rate constant to the ionic strength was found, indicative of hydroxyl-ion attack on barbiturate monoanion as a mechanism of degradation.

Effect of Copper (II)-Glycine Chelates on Degradation of Penicillin in Mildly Acid Solution

This study was undertaken to elucidate by in vitro kinetic analysis the role that Cu (II) ions, through complexation with an amino acid, may have in the degradation of the penicillins and the formation of the penicilloyl determinant. The data obtained indicated that in the presence of the Cu (II)-glycine chelates, penicillin is quantitatively hydrolyzed to penicilloic acid. This finding is in direct contrast to the much slower reaction between penicillin and glycine in the absence of Cu (II), in which the major degradation product is the penicilloamide. The overall observed rate constant can be represented by: k0 = Km[M][OH−] + Kmg [MG][OH−] in which Km and Kmg are the catalytic coefficients for Cu (II) and the 1:1 Cu (II)-glycine chelate, respectively, and [M] and [MG] represent the concentrations of free Cu (II) and the 1:1 chelate, respectively. The postulated mechanism involves the rapid formation of a ternary penicillin-Cu (II)-glycine complex, followed by a rate-limiting hydroxyl-ion attack.

Kinetics of Hydrolysis of Barbituric Acid Derivatives

The neutral and alkaline hydrolyses of barbituric acid and some of its substituted derivatives were followed spectrophotometrically. The rate‐pH profiles for all of the 5,5‐disubstituted barbiturates were similar. A different profile was observed for barbituric acid because of its comparatively low pKa1'. The rate‐pH profile of metharbital showed no curvature at high pH values, since the 1‐methyl substituent prevents the second possible proton dissociation. All profiles could be explained by hydroxyl‐ion attack on the undissociated and monoanion forms of the barbiturate, whereas the dianions are unreactive. The reactivity of the barbiturates was correlated with the Newman rule of six as a measure of steric influence on hydrolysis. A previously unmentioned, reversible system between the barbiturate and its ring‐opened malonuric acid derivative was observed and may be used to postulate that the fraction decomposing via1,6 ring opening is a function of pH rather than a direct consequence of a unique degradation pathway for the ionic form of the barbiturate. Ionic strength effects in the alkaline hydrolyses of amobarbital and phenobarbital increase the rate of barbiturate degradation by the attack of hydroxyl ion on the monoanion and/or its kinetic equivalent. The Arrhenius parameters for all compounds were determined.

Hydrolytic and Associative Behavior of Aromatic Amides in Aqueous Solution

Rate constants for alkaline hydrolysis (in 0.1N NaOH) of aromatic amides such as nicotinamide, benzamide, phenylacetamide, cinnamamide, and their corresponding N-alkyl substituted analogs were determined at 25°and 90°in order to investigate the effect of molecular structure on the stability of these amides against hydroxyl ion attack. Stability constants of these aromatic amide complexes with theophylline and 8-methoxycaffeine at 25°were also computed from phase-solubility data. The results have shown that cinnamamides are most stable against hydroxyl ion attack and formed the most stable complexes with the alkylxanthines while phenylacetamides are least stable in alkaline hydrolysis and least associative with alkylxanthines among benzene derivatives. Both hydrolytic behavior and associative tendency of these amides are discussed in relation to the extent of conjugation of the amide group with the rest of the molecule.

Acid and alkaline hydrolysis of glycopyranosyl fluorides

Hydrolyses of α- and β- D-glucopyranosyl, α- D-galactopyranosyl, α- D-xylopyranosyl, and β- L-arabinopyranosyl fluorides with perchloric acid and sodium hydroxide have been investigated over a range of temperatures and concentrations. All acid hydrolyses show pseudo-first-order kinetics and, except for β- D-glucopyranosyl fluoride, a dependence of log 10(rate) on H O with slopes of -0.76 to -0.85, and have positive entropies of activation, suggesting an Al mechanism. The relative rates of hydrolysis are similar to those of the corresponding methyl glycopyranosides and suggest the same cyclic carbonium-ion intermediate. β- D-Glucopyranosyl fluoride, in which the hydroxyl at C-2 is trans to the fluorine, has a negative entropy of activation, and hydrolysis may involve an intramolecular A2 mechanism. The alkaline hydrolyses present three different cases. α- D-Xylopyranosyl and β- L-arabinopyranosyl fluorides react initially with pseudo-first-order kinetics to give the free sugar as the only primary product. A plot of log 10(rate) against pH gave a slope close to 1.0, and the fluorides appear to react with nucleophilic attack of hydroxyl ion. α- D-Glucopyranosyl and α- D-galactopyranosyl fluorides also give pseudo-first-order kinetics initially, and show a fair dependence of log 10(rate) on H_with slope 1.0 over the range 1.0 to 5.0 N. These fluorides give a mixture of free sugar and 1,6-anhydro-β- D sugar as the products, and two simultaneous reactions probably occur, one involving direct nucleophilic attack by hydroxyl ion at C-1, and the other involving equilibrium ionization of the hydroxyl group at C-6 followed by intramolecular attack. β- D-Glucopyranosyl fluoride reacts 5000 times faster than the α-anomer, necessitating the use of second-order kinetics. The product is 1,6-anhydro-β- D-glucose, and the reaction must proceed through a 1,2-epoxide. All of the alkaline hydrolyses studied showed a negative entropy of activation.

Solvolysis of 5-Halouridines and Related Nucleosides

The neutral and alkaline solvolyses of uridine (UD) derivatives substituted in the 5 position with I (IUD), Br (BUD), Cl (CUD), and CH3 (MUD) were followed spectrophotometrically. The order of reactivity was IUD > BUD > CUD > UD ⋙ MUD (essentially stable). Ribosylbarbituric acid (RBA) was identified as a product of solvolysis of IUD and BUD in strong alkali and is itself unstable. The halouridines also degrade to nonchromophoric compounds. The rate-pH profiles for all the halouridines are similar and can be explained by hydroxyl ion attack on both the undissociated and dissociated halouridine. Hydroxyl ion attack on the undissociated species leads to the formation of nonchromophoric products. Hydroxyl ion attack on the dissociated species forms RBA. 5-Hydroxyuridine (OHUD) and dihydropyrimidines are postulated as intermediates. The lability of the halogen substituent enhances the ease of solvolysis. The rate of alkaline solvolysis of BUD is the same as the rate of bromide ion production and shows that the reaction intermediates are highly unstable. The arabino and lyxo derivatives of 5-fluorouracil are solvolyzed faster than all of the halouridines. The Arrhenius parameters for all compounds were determined.

Prediction of Stability in Pharmaceutical Preparations XV: Kinetics of Hydrolysis of 5-Trifluoromethyl-2′-deoxyuridine

The antiviral 5-trifluoromethyl-2′-deoxyuridine, F 3 TdR, is hydrolyzed by hydrogen ions and solvent to 5-trifluoromethyluracil, F 3 T, and deoxyribose. The F 3 T is readily hydrolyzed to 5-carboxyuracil by hydroxyl ion attack on the undissociated and anionic species. At elevated temperatures, 5-carboxyuracil is decarboxylated by hydroxyl ion catalysis to uracil. The F 3 TdR is readily hydrolyzed to 5-carboxy-2′-deoxyuridine by hydroxyl ion attack on the undissociated and anion species through an observable kinetic intermediate at high alkalinity, probably 5-hydroxydifluoromethyl-2′-deoxyuridine. The optimum pH range for stabilization is 1–4 where the half-life at 30° is 280 days. The material is readily degraded at pH 7.4 where 1.5 days is the half-life at 30°.

Solvolysis of 3, 4-dialkyl sydnones

The kinetics of solvolysis of various dialkyl sydnones: 3- tert -butyl-4-methyl, 3- n -propyl-4-ethyl, 3-ethyl-4-methyl, 3-isopropyl-4-ethyl, 3- n -propyl-4-methyl, and 3- n -propyl-4- n -butyl sydnone, have been studied spectrophotometrically as a function of HCl and NaOH concentrations, pH, and temperature. The reactivity on acid-catalyzed solvolysis decreased in the order cited with only the first compound exhibiting pH-independent solvolysis and high reactivity, about 600 times that of the others. The reactivities of the remainder were only over a threefold range. The order of reactivity tended to reverse on alkaline solvolysis within a similar range, where 3-ethyl-4-methylsydnone was 1.7 times more reactive than the equally reactive 3- n -propyl-4-ethyl, 3- n -propyl-4-methyl, and 3-isopropyl-4-ethyl sydnones. The 3- n -propyl-4- n -butylsydnone was half as reactive as this group, whereas the 3- tert -butyl-4-methylsydnone was one quarter as reactive. The presence of a-hydrogens on the alkyl substituted sydnones tends to stabilize such structures against hydrogen ion and water attack. This can be explained by postulating extended equilibria among tautomeric structures which decrease the effective concentration of the reactive intermediate. The 3-benzylsydnone demonstrates a reactivity to hydroxyl ion attack equivalent to the more reactive furfuryl sydnone where the electron-attracting powers of the rings are not completely inhibited by the intervening methylene groups. The acid-catalyzed solvolysis of 3-benzylsydnone is of the order of magnitude of other 3-alkyl sydnones with α-hydrogens. The observed second-order dependency of reactivity on hydrogen ion concentration may be assigned to the de-localization of the charge of the singly protonated species, due to the probability of many mesomeric forms with the benzyl substituent.

Kinetics of Solvolyses of Various N-Alkyl-N-nitrosoureas in Neutral and Alkaline Solutions

The N- alkyl- N -nitrosoureas possess antitumor activity but readily decompose at the pH of biological fluids with half-lives about 20 minutes at pH 7 and 37.5°. The effect of substituents, R, on the kinetics of solvolysis of synthesized R─N─(NO)─CO─NH 2 was determined in the phosphate buffer region, pH 6–7.8, as a basis for the proper design of biologically effective compounds. Spectrophotometric techniques were used over a range of several temperatures. The solvolytic rates were first order in substrate and hydroxyl ions and the log k -pH profile was linear with a slope of + 1.0. No solvent or general acid-base catalysis was observed, and salt effects were negligible. No significant differences in reactivities, entropies, or heats of activation were observed for R = methyl, ethyl, and butyl. The 2-methylpropyl was slightly more reactive. When R = allyl, phenethyl, and benzyl, a significant increase in reactivities was observed. The unsaturated substituents favored hydroxyl ion attack as expected. However, the cyclohexyl compound also had high reactivity to hydroxyl ion attack.