Abiotic Hydrolysis of Poly[(R)-3-hydroxybutyrate] in Acidic and Alkaline Media

Poly[(R)-3-hydroxybutyrate)], P(3HB), is the most common member of polyhydroxyalkanoates, the natural biopolyesters of intrinsic biodegradability and biocompatibility. Abiotic hydrolysis of P(3HB) was investigated in acid and base media by monitoring the formation of two monomer products, 3-hydroxybutyric acid (3HB) and crotonic acid (CA), from three types of P(3HB) samples, amorphous granules, irregular precipitates and solvent cast films. The soluble monomeric products were not detected in acid solutions (0.1 to 4 N H⁺), but measured as the major hydrolytic products in base solutions (0.1 to 4 N OH⁻). Unlike the protons as catalyst in both hydrolysis and esterification, hydroxyl anions were consumed during formation of carboxylate anions. The amorphous granules of P(3HB) were decomposed 80- to 100-fold faster than the precipitates and solvent cast films. The latter two had around 71% crystallinity. The hydrolysis of amorphous grannules exhibited a quasi 0^th-order reaction rate and the activation energy of saponification was 82.2 kJ/mol, silimar to those of the biotic hydrolysis of P(3HB) by enzymes and living cells.     

Kinetics of Alkaline Hydrolysis of Quaternary Phosphonium Salts. The Influence of Protic and Aprotic Solvents on the Hydrolysis of Alkyl Phenylphosphonium Salts

Abstract

Third order rate constants have been determined for the alkaline hydrolysis of four series of alkylphenylphosphonium salts and alkylphenylbenzylphosphonium salts at various temperatures in 50%–70% ^v/_v aqueous tetrahydrofuran and 70% ^v/_v aqueous methanol. Thermodynamic activation parameters have been calculated for the reactions of each substrate and the effects of varying the ratio of alkyl to phenyl groups have been compared, as well as the effects of changes in the nature of the alkyl group. Solvation, as revealed by trends in entropy of activation, plays a largely counter-balancing role with respect to enthalpy and energy of activation. The role of the isokinetic effect is discussed. In aqueous tetrahydrofuran, solvation effects on the hydrolyses of phosphonium salts change as the mole fraction of water changes, and for aqueous methanol the trends in the thermodynamic activation parameters actually reverse.     

A Comparison of Semi-Empirical and AB Initio Methods on the Hydrolysis of Phosphinates,Phosphonates, and Phosphates

The hydrolysis of phosphorus fluoridates was studied by semiempirical and ab initio methods. The reaction proceeds through a metastable intermediate separated from the reactants and products by transition structures. Both methods gave similar qualitative results; however, the first transition (formation of the trigonal bipyrimid intermediate) occurred earlier and the second (loss of F-) later with semiempirical methods. Including solvation in the calculations is critical. The AMSOL program generated reasonable energies especially when the limitations of the semiempirical Hamiltonian are considered. The Onsanger model was not a significant improvement over calculations on isolated molecules.     

Associative Versus Dissociative Mechanisms of Phosphate Monoester Hydrolysis: On the Interpretation of Activation Entropies

Phosphate monoester and anhydride hydrolysis is ubiquitous in biology, being involved in, amongst other things, signal transduction, energy production, and the regulation of protein function. Therefore, this reaction has understandably been the focus of intensive research. Nevertheless, the precise mechanism by which phosphate monoester hydrolysis proceeds remains controversial. Traditionally, it has been assumed and frequently implied that a near‐zero activation entropy is indicative of a dissociative pathway. Herein, we examine free‐energy surfaces for the hydrolysis of the methyl phosphate dianion and the methyl pyrophosphate trianion in aqueous solution. In both cases, the reaction can proceed through either compact or expansive concerted (A_ND_N) transition states, with fairly similar barriers. We have evaluated the activation entropies for each transition state and demonstrate that both associative and dissociative transition states have near‐zero entropies of activation that are in good agreement with experimental values. Therefore, we believe that the activation entropy alone is not a useful diagnostic tool, as it depends not only on bond orders at the transition state, but also on other issues that include (but are not limited to) steric factors determining the configurational volumes available to reactants during the reaction, solvation and desolvation effects that may be associated with charge redistribution upon approaching the transition state and entropy changes associated with intramolecular degrees of freedom as the transition state is approached.     

The Ortho Effect on the Acidic and Alkaline Hydrolysis of Substituted Formanilides

The kinetics of formanilides hydrolysis were determined under first‐order conditions in hydrochloric acid (0.01–8 M, 20–60°C) and in hydroxide solutions (0.01–3 M, 25 and 40°C). Under acidic conditions, second‐order specific acid catalytic constants were used to construct Hammett plots. The ortho effect was analyzed using the Fujita–Nishioka method. In alkaline solutions, hydrolysis displayed both first‐ and second‐order dependence in the hydroxide concentration. The specific base catalytic constants were used to construct Hammett plots. Ortho effects were evaluated for the first‐order dependence on the hydroxide concentration. Formanilide hydrolyzes in acidic solutions by specific acid catalysis, and the kinetic study results were consistent with the A_AC2 mechanism. Ortho substitution led to a decrease in the rates of reaction due to steric inhibition of resonance, retardation due to steric bulk, and through space interactions. The primary hydrolytic pathway in alkaline solutions was consistent with a modified B_AC2 mechanism. The Hammett plots for hydrolysis of meta‐ and para‐substituted formanilides in 0.10 M sodium hydroxide solutions did not show substituent effects; however, ortho substitution led to a decrease in rate constants proportional to the steric bulk of the substituent.     

Phosphine and Thiophene Cyclopalladated Complexes: Hydrolysis Reactions in Strong Acidic Media

The mechanisms for the hydrolysis of organopalladium complexes [Pd(CNN)R]BF₄ (R=P(OPh)₃, PPh₃, and SC₄H₈) were investigated at 25 °C by using UV/Vis absorbance measurements in 10 % v/v ethanol/water mixtures containing different sulphuric acid concentrations in the 1.3–11.7 M range. In all cases, a biphasic behavior was observed with rate constants k_1obs, which corresponds to the initial step of the hydrolysis reaction, and k_2obs, where k_1obs>k_2obs. The plots of k_1obs and k_2obs versus sulfuric acid concentration suggest a change in the reaction mechanism. The change with respect to the k_1obs value corresponds to 35 %, 2 %, and 99 % of the protonated complexes for R=PPh₃, P(OPh)₃, and SC₄H₈, respectively. Regarding k_2obs, the change occurred in all cases at about 6.5 M H₂SO₄ and matched up with the results reported for the hydrolysis of the 2‐acetylpyridinephenylhydrazone (CNN) ligand. By using the excess acidity method, the mechanisms were elucidated by carefully looking at the variation of k_i,_obs (i=1,2) versus ${c_{{\rm{H}}^ + } }$ . The rate‐determining constants, k_0,A‐1, k_0,A‐2, and k_0,A‐SE2 were evaluated in all cases. The R=P(OPh)₃ complex was most reactive due to its π‐acid character, which favors the rupture of the trans nitrogen–palladium bond in the A‐2 mechanism and also that of the pyridine nitrogen–palladium bond in the A‐1 mechanism. The organometallic bond exerts no effect on the relative basicity of the complexes, which are strongly reliant on the substituent.     

Selective Alkaline Protease Catalyzed Hydrolysis of Peptide Esters

Procedures for preparing C-terminal free peptides from hydrolysis of its corresponding methyl or benzyl esters catalyzed by alkaline protease has been developed. N-protected peptides having side-chain ester protecting groups or successive hydrophobic amino acid residues in its sequence are hydrolyzed selectively at C-terminal only and leave other bonds (β and γ- ester or peptide bonds) intact. Compounds which cause a side reaction in base mediated saponification could be hydrolyzed safely by this procedure. Products of this hydrolysis are useful intermediates for fragments coupling in the solid phase peptide synthesis.     

溶菌酶降解壳聚糖条件的研究

研究了溶茵酶对壳聚糖的降解条件,结果表明：脱乙酰度约70％的壳聚糖较易被溶菌酶水解;水解反应的最适温度为55℃、pH值为4．0,低速摇床振荡对水解有利;在壳聚糖水解初期,溶液中还原糖浓度迅速增加,0．5h后水解速率逐渐减慢,至8h后还原糖浓度的增加已很缓慢;酶解液中还原糖的生成量瞳壳聚糖及溶茵酶浓度的增加而增大,当壳聚糖溶液浓度为20mg／mL、溶茵酶浓度为2．48mg／mL时,水解6h后,还原糖的含量可达6．758mmol／L。水解6h后酶解液中还原糖浓度与壳聚糖的浓度呈线性关系。     

Mechanism of Alkaline Hydrolysis of Diazepam

Diazepam (1) is a frequently prescribed hypnotic/anxiolytic drug in worldwide use. Compound 1 is hydrolyzed in alkaline medium to form 2-methylamino-5-chlorobenzophenone imine (2) and 2-methylamino-5-chlorobenzophenone (3) ; the ratio of 2:3 increases with increasing NaOH concentration (J. Pharm. Sci. 85, 745–748, 1996). The mechanism in the conversion of 1 to 2 and 3 via various intermediates is the subject of this report. Results of hydrolysis kinetics and structural identification of some intermediate products indicated an initial hydroxide attack at the C2-carbonyl carbon of 1 , resulting in the formation of a dioxide ( 7 , 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2,2-dioxide). Compound 7 was characterized by proton NMR spectroscopy and via its monomethyl ether ( 8 , 7-chloro-1,3-dihydro-2-hydroxy-2-methoxy-l-methyl-5-pheny]-2H-1,4-benzodiazepine). The seven-member diazepine ring of 7 opened at the N1-C2 bond to form a glycinate [ 5 , 2-methylamino-5-chloro-α-(phenylhenzylidene)glycinate]. Compound 7 (and/or 5 ) underwent an additional hydroxide attack at the C5-N4 imine bond to form a tetrahedral intermediate, which decomposed to form 2 and 3 .     

Probing the Catalytically Active Species in POM-Catalysed DNA-Model Hydrolysis**

Phosphoester hydrolysis is an important chemical step in DNA repair. One archetypal molecular model of phosphoesters is para-nitrophenylphosphate (pNPP). It has been shown previously that the presence of molecular metal oxide [Mo₇O₂₄]⁶⁻ may catalyse the hydrolysis of pNPP through the partial decomposition of polyoxomolybdate framework resulting in a [(PO₄)₂Mo₅O₁₅]⁶⁻ product. Real-time monitoring of the catalytic system using electrospray ionisation mass spectrometry (ESI-MS) provided a glance into the species present in the reaction mixture and identification of potential catalytic candidates. Following up on the obtained spectrometric data, Density Functional Theory (DFT) calculations were carried out to characterise the hypothetical intermediate [Mo₅O₁₅(pNPP)₂(H₂O)₆]⁶⁻ that would be required to form under the hypothesised transformation. Surprisingly, our results point to the dimeric [Mo₂O₈]⁴⁻ anion resulting from the decomposition of [Mo₇O₂₄]⁶⁻ as the active catalytic species involved in the hydrolysis of pNPP rather than the originally assumed {Mo₅O₁₅} species. A similar study was carried out involving the same species but substituting Mo by W. The mechanism involving W species showed a higher barrier and less stable products in agreement with the non-catalytic effect found in experimental results.     

Lactone enol cation-radicals: gas-phase generation,structure, energetics,and reactivity of the ionized enol of butane-4-lactone

The cation-radical of 2-hydroxyoxol-2-ene (1(+*)) represents the first lactone enol ion whose structure and gas-phase ion chemistry have been studied by experiment and theory. Ion 1(+*) was generated by the McLafferty rearrangement in ionized 2-acetylbutane-4-lactone and characterized by accurate mass measurements, isotope labeling, metastable ion and collisionally activated dissociation (CAD) spectra. Metastable 1(+*) undergoes competitive losses of H-4 and CO that show interesting deuterium and (13)C isotope effects. The elimination of CO from metastable 1(+*) shows a bimodal distribution of kinetic energy release and produces (*)CH(2)CH(2)CHdbond;OH(+) (14(+*)) and CH(3)CHdbond;CHOH(+*) (15(+*)) in ratios which are subject to deuterium isotope effects. Ab initio calculations at the G2(MP2) level of theory show that 1(+*) is 105 kJ mol(-1) more stable than its oxo form, [butane-4-lactone](+*)(2(+*)). The elimination of CO from 1(+*) involves multiple isomerizations by hydrogen migrations and proceeds through ion-molecule complexes of CO with 14(+*) and 15(+*). In addition, CO is calculated to catalyze an exothermic isomerization 14(+*) --> 15(+*) in the ion-molecule complexes. Multiple consecutive hydrogen migrations in metastable 1(+*), as modeled by RRKM calculations on the G2(MP2) potential energy surface, explain the unusual deuterium kinetic isotope effects on the CO elimination.     

Synthesis and Crystal Structure of a Novel Lactone Derived from Dehydroabietic Acid

A novel lactone derived from dehydroabietic acid,C20H21BrO4,has been charac-terized by IR,1H NMR,13C NMR and single-crystal X-ray diffraction method.It crystallizes in orthorhombic,space group P212121 with a = 6.4195(15),b = 11.535(3),c = 24.654(6) ,V = 1825.5(7) 3,Z = 4,Mr = 405.28,Dc = 1.475 g/cm3,λ = 0.71075 ,μ(MoKα) = 2.27 mm-1,F(000) = 832,the final R = 0.024 and wR = 0.045 for 2152 observed reflections with I 2σ(I).The molecules of lactone are mainly linked through intermolecular hydrogen bonds.     

Nucleophilic Substitution at Tricoordinate Sulfur—Alkaline Hydrolysis of Optically Active Dialkoxysulfonium Salts: Stereochemistry,Mechanism and Reaction Energetics

Optically active dialkoxyisopropylsulfonium salts were obtained by methylation (ethylation) of optically active alkyl isopropanesulfinates using methyl (ethyl) trifluoromethanesulfonate. Alkaline hydrolysis of a series of methoxy(alkoxy)sulfonium salts afforded the two sulfinate products methyl isopropanesulfinate and alkyl isopropanesulfinate, both formed with a slightly prevailing inversion of configuration at the sulfur atom. DFT calculations revealed that this substitution reaction proceeded stepwise according to an addition-elimination (A–E) mechanism involving the formation of high tetracoordinate S^IV sulfurane intermediates. In addition, the DFT calculations showed that recombination of the hydroxy anion with the methoxy(alkoxy)sulfonium cation—leading to the parallel formation of the two most stable primary sulfuranes, with the hydroxy and alkoxy groups in apical positions and their direct decomposition—is the most energetically favorable pathway.     

Efficient Syntheses of Traumatic Lactone and Rhizobialide

Herein, we report the total synthesis of traumatic lactone and rhizobialide by utilizing allenoic acid to construct the lactone ring. The key starting materials, allenoic acids, could be prepared by the ATA (allenation of terminal alkynes) of a terminal alkyne with an aldehyde that contained a protected hydroxyl group followed by hydrolysis. Importantly, the asymmetric synthesis could be realized just by replacing racemic diphenylprinol with (R)- or (S)-diphenylprinol to deliver the optically active allenoate.     

Enzymatic Synthesis of Phosphoric Monoesters with Alkaline Phosphatase in Reverse Hydrolysis Conditions

Abstract

Title compounds were synthesized on a preparative scale using alkaline phosphatase, orthophosphoric monoester phosphohydrolase E.C. 3.1.3.1, in reverse hydrolysis conditions. Optimization for one of the 25 Fhosphoryl acceptors hvestfgated (glycerol) shovs that up to 55% synthesis yield can be obtained using a large excess of substrate, conditions in which the enzymatic activity remains high. From the results obtained with different phosphoryl group donors, phosphate, pyrophosphate and polyphosphates and with enzymes of different sources, it comes up that the best results are obtained with pyrophosphate and with the weakly purified calf intestine alkaline phosphatase. The extent of enzymatic hydrolysis of the donor can be reduced owing to the existence of two different pH optima for the two reactions, phosphorylation and hydrolysis. The synthesis can be also performed using inert co-solvents which allow to reduce the amount of acceptor used, as long as Zn⁺⁺ is added to the reaction medium. The results are discussed in terms of the catalytic mechanism of alkaline phosphatase.     

表面活性剂复配混合胶束对酯碱性水解反应的影响

应用紫外分光光度法和热动力学法研究了芳香酸酯和正脂肪酸乙酯在表面活性剂复配事胶束（ＳＤＳ－Ｂ３５，ＤＴＡＢ－Ｂｒｉｊ－３５，ＴＴａｂ－Ｂｒｉｊ３５，ＣＴＡＢ－Ｂｒｉｊ３５，ＣＢＡＢ－Ｔｒｉｔｏｎ Ｘ－１００，ＳＤＳ－Ｔｒｉｔｏｎ Ｘ－１００）中的碱性水解反应，复配胶束对酯的碱性水解反应起禁阻作用，其禁阻作用比单一胶束的禁阻作用强，并讨论了复配胶束对酯碱解起禁阻作用的原因。     

Voltammetric Sensing of Amino Acids in the Presence of Cu(II) in Acidic and Alkaline Solutions

A number of amino acids have been determined at carbon film electrodes in the presence of copper. Strongly acidic, 0.1 M HCl, in the presence of 0.1 mM Cu(II), as well as alkaline, 0.1 M NaOH, solution permit successful measurement of individual amino acids, clearer separation between oxidation of Cu and Cu‐complexes occurring in alkaline solution. Electrochemical impedance showed that Cu(II) facilitates charge transfer, particularly in alkaline medium. Square wave voltammetry with preconcentration increased the response compared to linear sweep voltammetry. Protein hydrolysis rates were monitored through determination of amino acids produced by decomposition, injecting samples into alkaline electrolyte solution.     

Acceleration by Double Activation Catalysis and its Negation with Rising Temperature in Hydrolysis of Cellobiose with Phthalic and Hydrochloric Acids

Double activation catalysis was experimentally observed in hydrolysis of cellobiose catalyzed simultaneously with phthalic and hydrochloric acids, confirming earlier theoretical prediction known from literature. Both acids can catalyze the reaction individually, and contribution of the double-activation pathway to the total reaction rate declines as temperature increases. In fact, above a certain temperature, the hydrolysis rate in presence of both acids becomes lower than the sum of the rates for the two acids acting individually. A kinetic model is proposed to explain this transition between double-activated catalysis and inhibition. The trend of declining contribution of cooperative catalytic pathway with rising temperature is theorized to be generally applicable for any reaction with a pathway involving simultaneous action of two catalysts when either of them can individually catalyze the reaction.     

The Mechanisms of Acid-Catalyzed Hydrolysis of N-(4-Substituted Arylthio) Phthalimides

Abstract

The acid-catalyzed hydrolysis of N-(4-substitutedarylthio)phthalimides was studied in aqueous solutions of sulfuric, perchloric, and hydrochloric acids at 40.0 ± 0.1 °C. Analysis of the data by the excess acidity method, activation parameters, and substituent effects indicates hydrolysis by an A-2 mechanism at low acidity. At higher acidities, a changeover to an A-1 mechanism is observed.

GRAPHICAL ABSTRACT