Neutral Hydrolysis Research Articles

Simultaneous glycolysis and hydrolysis of polyethylene terephthalate and characterization of products by differential scanning calorimetry

Simultaneous glycolysis and neutral hydrolysis of waste polyethylene terephthalate (PET) has been carried out at 170 and 190 °C with constant amount of ethylene glycol (EG) and increasing amounts of water, in the presence of xylene. The organic solvent made it possible to employ very low amounts of reactants as well as application of lower temperatures and pressures in contrast with previous methods, yielding intermediates suitable for PET or other polymeric materials. These intermediates were characterized by acid value (AV), hydroxyl value (HV) determinations as well as by differential scanning calorimetry (DSC). A water soluble crystallizable fraction with high purity, consisting of mono 2-hydroxy ethyl ester of terephthalic acid (monohydroxyethyl terephthalate, MHT) monomer has been obtained with significant yield and its polymerization tendency has been compared with that of bis(2-hydroxy ethyl) terephthalate (BHET) by application of multiple heating/cooling cycles in DSC.

35S]-Labeling of the Salmonella typhimurium glutathione pool to assess glutathione-mediated DNA binding by 1,2-dibromoethane

Biotransformation of drugs and environmental chemicals to reactive intermediates is often studied with the use of radiolabeled compounds that are synthesized by expensive and technically difficult procedures. In general, glutathione (GSH) conjugation serves as a detoxification mechanism, and conjugation of reactive intermediates with GSH is often a surrogate marker of reactive species formation. However, several halogenated alkanes can be bioactivated by GSH to yield highly reactive GSH conjugates, some of which are DNA-reactive (e.g. conjugates of 1,2-dibromoethane). The purpose of this study was to metabolically radiolabel the in vivo GSH pool of Salmonella typhimurium with a [ 35S]-label and to examine the GSH-mediated bioactivation of a model haloalkane, 1,2-dibromoethane, by measuring the binding of [ 35S]-label to DNA. The strain of Salmonella used in this study had been transformed previously with the gene that codes for rat glutathione transferase theta 1-1 (GSTT1-1), an enzyme that can catalyze formation of genotoxic GSH conjugates. Bacteria were grown to mid-log phase and then incubated with [ 35S]- l-cysteine in minimal medium (thio-free) until stationary phase of growth was reached. At this stage, the specific activity of Salmonella GSH was estimated to be 7.1 mCi/mmol by derivatization and subsequent HPLC analysis, and GSTT1-1 enzyme activity was still demonstrable in Salmonella cytosol following growth in a minimal medium. The [ 35S]-labeled bacteria were then exposed to 1,2-dibromoethane (1 mM), and the Salmonella DNA was subsequently purified to quantify [ 35S]-binding to DNA. The amount of [ 35S]-label that was covalently bound to DNA in the GSTT1-1-expressing Salmonella strain (33.2 nmol/mg DNA) was sevenfold greater than that of the control strain that does not express GSTT1-1. Neutral thermal hydrolysis of the DNA yielded a single [ 35S]-labeled adduct with a similar t R as S-[2-( N 7-guanyl)ethyl]GSH, following HPLC analysis of the hydrolysate. This adduct accounted for 95% of the total [ 35S]-label bound to DNA. Thus, this [ 35S]-radiolabeling protocol may prove useful for studying the DNA reactivity of GSH conjugates of other halogenated alkanes in a cellular context that maintains GSH at normal physiological levels. This is also, to our knowledge, the first demonstration of de novo incorporation of [ 35S]- l-cysteine into the bacterial GSH pool.

Hydrolysis of waste polyethylene terephthalate and characterization of products by differential scanning calorimetry

Neutral hydrolysis of waste polyethylene terephthalate (PET) has been carried out with different amounts of water and different catalysts, in the presence of xylene. The organic solvent made it possible to employ very little amounts of water, lower temperatures and pressures and providing concentrated ethylene glycol (EG) solutions in contrast with previous methods, yielding intermediates suitable for PET preparation. These intermediates were characterized by FTIR spectroscopy, acid value (AV), hydroxyl value (HV), viscosity average molecular weight ( M v ) determinations as well as by DSC. Multiple heating/cooling runs in DSC apparatus were carried out and a deconvolution procedure was applied using Haarhoff–Van der Linde (HVL) function to verify the presence of the same components and also to compare polymerization tendency of these various hydrolysis products.

Aldehydic DNA lesions induced by catechol estrogens in calf thymus DNA.

The primary purpose of this research is to examine the hypothesis that reactive oxygen species generated by estrogen quinonoids are the main source for the formation of aldehydic DNA lesions (ADL) in genomic DNA. ADL induced by quinonoid metabolites of 17beta-estradiol (E2), e.g. 4-hydroxyestradiol (4-OH-E2), 2-hydroxyestradiol (2-OH-E2), estrogen-3,4-quinones (E2-3,4-Q) and estrogen- 2,3-quinone (E2-2,3-Q), were investigated in calf thymus DNA (CT-DNA) under physiological conditions. The abasic sites resulting from the spontaneous depurination-depyrimidination of the modified bases and the aldehydic base and sugar lesions resulting from the oxidative damage to deoxyribose moieties in the DNA molecules were measured by an aldehyde reactive probe and were estimated as the number of ADL per 106 nucleotides. With the addition of NADPH (100 micro M) and Cu(II) (20 micro M), nanomolar levels (100 nM) of 4-OH-E2 and 2-OH-E2 induced approximately 10-fold increases in the number of ADL over control (P<0.001). In parallel, increases in 8-oxoguanine were detected in DNA exposed to 4-OH-E2 and 2-OH-E2 (100 nM) plus Cu(II) and NADPH. Further investigation indicated that the ADL induced by estrogen catechols plus Cu(II) and NADPH were causally involved in the formation of hydrogen peroxide and Cu(I). Both E2-2,3-Q and E2-3,4-Q alone induced a 2-fold increase in the number of ADL over control (P<0.05) in CT-DNA at high concentrations (1 mM). Neither neutral thermal hydrolysis nor lower ionic strength of the reaction medium induced further increases in the number of ADL in E2-3,4-Q-modified CT-DNA. Conversely, with the inclusion of Cu(II) and NADPH, both E2-3,4-Q and E2-2,3-Q (1 micro M) induced parallel formation of DNA single strand breaks and approximately 20-fold increases in the number of ADL over control (P < 0.001). The data also demonstrated that the ADL induced by estrogen quinones with and without the presence of Cu(II) and NADPH contain 69 and 78% putrescine-excisable ADL in CT-DNA, respectively. Additionally, results of the ADL cleavage assay indicate that the ADL induced by estrogen quinones plus Cu(II) and NADPH in CT-DNA were predominantly T7 exonuclease-excisable (50%) and exonuclease III- excisable (20%) ADL, whereas the intact ADL, and other ADL accounted for 5 and 25%, respectively. These results suggest that the ADL induced by estrogen quinones in CT-DNA are derived from oxidative events rather than depurination/depyrimidination of labile estrogen quinone-DNA adducts. Overall, our results are at variance with the idea that depurination of estrogen quinone-DNA adducts is the major source for the formation of ADL in genomic DNA. We hypothesize that in addition to DNA adducts and oxidized bases, the ADL induced by estrogen quinonoid-mediated oxidative stress may play a role in estrogen-induced carcinogenicity.

Identification of adducts formed by pyridyloxobutylation of deoxyguanosine and DNA by 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone, a chemically activated form of tobacco specific carcinogens.

The tobacco specific carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are metabolically activated to 4-oxo-4-(3-pyridyl)-1-butanediazohydroxide (7), which is known to pyridyloxobutylate DNA. A substantial proportion of the adducts in this DNA releases 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB, 11) under various hydrolysis conditions, including neutral thermal hydrolysis. These HPB-releasing DNA adducts have been detected in target tissues of animals treated with NNK and NNN as well as in lung tissue from smokers. Although their presence in pyridyloxobutylated DNA was conclusively demonstrated 15 years ago, their structures have not been previously determined. We investigated this question in the present study by determining the structures of products formed in reactions with dGuo and DNA of 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKCH(2)OAc, 3), a stable precursor to 7. Reaction mixtures from NNKCH(2)OAc and dGuo were analyzed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) with selected ion monitoring at m/z 415. A major peak was detected and identified as 7-[4-oxo-4-(3-pyridyl)but-1-yl]dGuo (37) by its ESI-MS fragmentation pattern and by neutral thermal hydrolysis, which converted it to 11 and 7-[4-oxo-4-(3-pyridyl)but-1-yl]Gua (26). The latter was identified by comparison to synthetic 26 using LC-ESI-MS with selected ion monitoring at m/z 299, M + 1 of 26. Further evidence was obtained by NaBH(4) reduction of 26 to 7-[4-hydroxy-4-(3-pyridyl)but-1-yl]Gua, which was also matched with a standard. Adduct 37 was similarly identified in enzyme hydrolysates of DNA reacted with NNKCH(2)OAc, accounting for 30-35% of the HPB-releasing adducts in this DNA. Several other adducts resulting from pyridyloxobutylation of the N(2)- and O(6)-positions of Gua were also identified as products in the dGuo or DNA reactions by comparison to standards; their concentrations were considerably less than that of 37. These adducts were N(2)-[4-oxo-4-(3-pyridyl)but-1-yl]dGuo (23), N(2)-[4-oxo-4-(3-pyridyl)but-2-yl]dGuo (25), N(2)-[2-(3-pyridyl)tetrahydrofuran-2-yl]dGuo (31a) (or its open chain tautomer 31b), and O(6)-[4-oxo-4-(3-pyridyl)but-1-yl]dGuo (10). Adducts 23, 25, and 10 did not release HPB upon neutral thermal hydrolysis. The results of this study provide the first structural identification of an HPB-releasing DNA adduct of the tobacco specific nitrosamines NNK and NNN.

Effect of hydrolysis pretreatment on fat degradation during anaerobic digestion of slaughterhouse wastewater

Slaughterhouse wastewater containing pork fat particles with initial average particle sizes ( D in) ranging from 60 to 450 μm was pretreated at 25 °C for 5.5 h with 250 mg/l of Pancreatic Lipase 250 (PL-250). Approximately 35% of substrate neutral fat was hydrolysed during pretreatment. Enzyme pretreated and control substrates were fed to anaerobic sequencing batch reactors (ASBRs) operated at 25 °C. During anaerobic treatment, the first-order neutral fat hydrolysis rate averaged 0.50±0.13 and 0.63±0.07/d for pretreated and control substrates, respectively. There was no significant particle size or pretreatment effect on pork fat hydrolysis rate in the ASBRs. Higher free long-chain fatty acid (LCFA) concentrations in the pretreated than control substrates resulted in slightly increased LCFA removal rate at the onset of anaerobic digestion with pretreated substrate. However, pretreatment had only a small overall effect on fat particle digestion at 25 °C, marked by a decrease of about 5% in digestion time to achieve 80% reduction in neutral fat and LCFA concentration.

The kinetics of the homogeneous benzylation of potato starch in aqueous solutions

The reaction rates in the base-catalysed benzylation of gelatinized aqueous starch (4 wt%), by benzylchloride (BzCl), were investigated in a semibatch reactor at temperatures ranging from 50 to 80 °C. The desired starch benzylation reaction is accompanied by an undesired parallel base-catalysed hydrolysis reaction of benzylchloride. The rate equations are: Starch benzylation : −R BzCl =k 2c RO −c BzCl Benzylchloride hydrolysis : −R BzCl =k 3c OH −c BzCl Neutral benzylcholoride hydrolysis : −R BzCl =k 4c H 2 O c BzCl where c BzCl is the benzylchloride concentration, c RO − is the concentration of the dissociated starch hydroxyl group and c OH − is the sodium hydroxide concentration; k is the reaction rate constant. The temperature dependency of the rate constants was measured as: k 2=4.21×10 11 e (−86.2×10 3/RT) k 3=2.62×10 8 e (−85.5×10 3/RT) k 4=9.72×10 9 e (−76.9×10 3/RT) where R=8.31441 J/(mol K).

Theoretical Study on the Alkaline and Neutral Hydrolysis of Succinimide Derivatives in Deamidation Reactions

The hydrolysis of a succinimide derivative in alkali and neutral media has been studied at the B3LYP/6-31+G* level. Stepwise and concerted mechanisms have been considered in a vacuum. Both mechanisms have been also studied in solution by means of integral equation formalism-polarizable continuum model with a single point calculation. In basic medium, the stepwise mechanism consists of a bond cleavage and a subsequent rotation of the hydroxyl group that require 8.6 and 3.0 kcal/mol, respectively. For the concerted hydrolysis in the same medium, the barrier is 9.8 kcal/mol. In neutral medium, the hydrolysis is facilitated by the presence of a polar continuum, whereas in basic medium, the polar environment hinders hydrolysis of succinimide.

Perfluoropolyether alkyl diesters: Structure effects of the alkyl group on the kinetics of the hydrolysis reactions

AbstractA series of perfluoropolyether bis‐carboxylic esters was synthesized and their hydrolytic stability investigated. Their formula is ROOCCF2O(CF2CF2O)p(CF2O)qCF2COOR, where p/q = 1.07 and p + q = 2.94. The alkyl group, R, varied both in terms of steric hindrance and electron‐withdrawing ability. Kinetic and thermodynamic data were obtained under homogeneous conditions and compared to a fully hydrogenated ester having a closely related structure CH3(CH2)3OOCCH2O(CH2CH2O)nCH2COO(CH2)3CH3, where n̄ = 10.6. Neutral ester hydrolysis (NEH) conditions were selected with methyl ethyl ketone as a solvent and a 3–4:1 water/ester ratio. The course of the reaction was monitored by 19F NMR or 1H NMR (when R = CH3CH2). Results indicated that the hydrolysis of fluorinated esters, with alkyl aliphatic substituents, is governed by steric hindrance of the substituents. Two distinctive kinetic regimes were observed. The first one, at low conversion, was characterized by lower kinetic constants and related to true NEH conditions. The second regime appeared at higher conversion when acidic autocatalysis dictated the reaction behavior. This is the only observed mechanism when esters more sensitive to the hydrolysis are considered. In these cases, polar factors prevail over steric considerations. Finally, all fluorinated esters of the class (I) showed a much higher reactivity than the hydrogenated ester whose hydrolysis took place only in the presence of a strong acidic catalyst. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 4266–4280, 2002

Association of Hydrotropes in Aqueous Solution Studied by Reaction Kinetics

The effect of added hydrotropes on the rates of neutral hydrolysis for 1-benzoyl-3-phenyl-1,2,4-triazole 1 has been studied, together with the concentration dependence of the 1H NMR spectra of the hydrotropes in aqueous solution. Hydrotropes include sodium 4-alkylbenzenesulfonates 2a - e, sodium 4-methoxybenzenesulfonate 2f, sodium 4-hydroxybenzenesulfonate 2g, cesium benzenesulfonate 3, benzamidinium chloride 4, phenyltrimethylammonium bromide 5a, and benzyltrimethylammonium bromide 5b. All hydrotropes, except 2g, induce strong rate-retarding effects, indicative of strong interactions with 1 and of remarkably strong hydrophobic interactions between aromatic moieties. Most hydrotropes show neither spectroscopic nor kinetic evidence for cooperative aggregation in the concentration range studied, i.e., from 0 to 1.4 mol kg-1. Cooperative aggregation is absent because the hydrophobic moieties are too small for hydrophobic interactions to overcome electrostatic repulsion. Lack of aggregation results in high availability of hydrophobic binding sites, thereby accounting for the high solubilizing power characteristic for hydrotropes. However, sodium 4-n-propylbenzenesulfonate 2d and sodium 4-nbutylbenzenesulfonate 2e show cooperative self-association forming highly dynamic loose micellar-type structures.

Effect of coordinated water on the mechanism of neutral hydrolysis of silicon dioxide in gas phase: a first principles study

Ab initio quantum chemical studies are reported at the B3LYP/6-311++G(d,p), MP2/6-311++G(d,p), and MP2/cc-pVTZ levels for the neutral hydrolysis of silicon dioxide in gaseous phase. These mechanistic studies predict that hydrolysis of silicon dioxide to orthosilicic acid is significantly controlled by the coordinated water molecule at the silicon. The catalytic activity of second water molecule coordinated to silicon lowers the reaction barrier by more than 50% than the first water molecule. The overall reaction is a low barrier process with barrier heights <2 kcal/mol at the MP2/cc-pVTZ level. This is in contrast to the hydration of carbon dioxide, where the second coordination at the carbon is less feasible. At all the three levels of calculations, the reaction follows similar trend.

Neutral fat hydrolysis and long‐chain fatty acid oxidation during anaerobic digestion of slaughterhouse wastewater

Neutral fat hydrolysis and long-chain fatty acid (LCFA) oxidation rates were determined during the digestion of slaughterhouse wastewater in anaerobic sequencing batch reactors operated at 25 degrees C. The experimental substrate consisted of filtered slaughterhouse wastewater supplemented with pork fat particles at various average initial sizes (D(in)) ranging from 60 to 450 microm. At the D(in) tested, there was no significant particle size effect on the first-order hydrolysis rate. The neutral fat hydrolysis rate averaged 0.63 +/- 0.07 d(-1). LCFA oxidation rate was modelled using a Monod-type equation. The maximum substrate utilization rate (kmax) and the half-saturation concentration (Ks) averaged 164 +/- 37 mg LCFA/L/d and 35 +/- 31 mg LCFA/L, respectively. Pork fat particle degradation was mainly controlled by LCFA oxidation rate and, to a lesser extent, by neutral fat hydrolysis rate. Hydrolysis pretreatment of fat-containing wastewaters and sludges should not substantially accelerate their anaerobic treatment. At a D(in) of 450 microm, fat particles were found to inhibit methane production during the initial 20 h of digestion. Inhibition of methane production in the early phase of digestion was the only significant effect of fat particle size on anaerobic digestion of pork slaughterhouse wastewater. Soluble COD could not be used to determine the rate of lipid hydrolysis due to LCFA adsorption on the biomass.

A mechanistic study of a topochemical dihydrogen to covalent bonding transformation

Solid-state decomposition of the dihydrogen-bonded complex LiBH 4 ·TEA (TEA: triethanolamine) into a covalent material was probed via 11B MAS NMR and FT-IR spectroscopies, as well as single-crystal and powder X-ray diffraction and optical microscopy. Based on variable-temperature kinetic analysis and H/D exchange experiments, H 2 loss appears to occur via rate-limiting proton transfer from the TEA’s OH groups to the BH 4 – anions at the reactant/product interface. The activation parameters ΔH ‡=84±10 kJ/mol and ΔS ‡=−70±26 J/(mol K) are comparable to those found for neutral aqueous hydrolysis of BH 4 −, suggesting similar mechanisms for the solid and solution decompositions.

Kinetic evidence for hydrophobically stabilized encounter complexes formed by hydrophobic esters in aqueous solutions containing monohydric alcohols.

The pH-independent hydrolysis of four esters, p-methoxyphenyl 2,2-dichloroethanoate (1a), p-methoxyphenyl 2,2-dichloropropanoate (1b), p-methoxyphenyl 2,2-dichlorobutanoate (1c), and p-methoxyphenyl 2,2-dichloropentanoate (1d), in dilute aqueous solution has been studied as a function of the molality of added cosolutes ethanol, 1-propanol, and 1-butanol. The rate constants for the neutral hydrolysis decrease with increasing cosolute concentration. These kinetic medium effects respond to both the hydrophobicity of the ester and of the monohydric alcohol. The observed rate effects were analyzed using both a thermodynamic and a kinetic model. The kinetic model suggests a molecular picture of a hydrophobically stabilized encounter complex, with equilibrium constants K(ec) often smaller than unity, in which the cosolute blocks the reaction center of the hydrolytic ester for attack by water. The formation of these encounter complexes leads to a dominant initial-state stabilization as follows from the thermodynamic model. Decreases in both apparent enthalpies and entropies of activation for these hydrolysis reactions correspond to unfavorable enthalpies and favorable entropies of complexation, which confirms that the encounter complexes are stabilized by hydrophobic interactions.

Effect of Operating Parameters and Screw Geometry on Micromixing in a Co-Rotating Twin-Screw Extruder

Aproduct distribution of a system of two parallel chemical reactions, consisting of acid-base neutralization and ester hydrolysis, was used to characterize mixing in a corotating twin-screw extruder. The experimental system was supplied through different feeding ports with the acid-ester premixture and the base solution respectively. A model of laminar micromixing was applied to correlate the screw speed and the extruder throughput with the average rate of viscous deformation for three screw geometries.

Hydrolysis of terbufos using simulated environmental conditions: rates, mechanisms, and product analysis.

This study focuses on the hydrolysis of terbufos, an organophosphorus pesticide. Combining GC-MS and wet chemistry methods, di-tert-butyl disulfide and formaldehyde were identified and quantified as major degradation products. Diethyl dithiophosphate was also indirectly identified as a degradation product under alkaline conditions. Hydrolysis rate constants of terbufos under homogeneous conditions were comparable to those of phorate and show relative insensitivity to pH under slightly acidic to neutral pH conditions, as the observed rate constants varied only in the range of (4.5-5.0) x 10(-6) s(-1) between pH 5.7 and 9.4; neutral hydrolysis is thus the most dominant hydrolysis pathway of terbufos in ambient waters. The mechanisms for terbufos hydrolysis and the formation of the major products and their temporal profiles are discussed. To assess the environmental impact of degradation products of this widely used pesticide, Microtox was used to analyze the toxicity of terbufos and two of its degradation products: diethyl dithiophosphate and di-tert-butyl disulfide; the EC(50) of terbufos was found to be >17 microM, whereas the EC(50) of di-tert-butyl disulfide was 1.3 microM.

Reactions of alpha-acetoxy-N-nitrosopyrrolidine with deoxyguanosine and DNA.

We investigated the reactions of alpha-acetoxy-N-nitrosopyrrolidine (alpha-acetoxyNPYR) with dGuo and DNA. Alpha-acetoxyNPYR is a stable precursor to the major proximate carcinogen of NPYR, alpha-hydroxyNPYR (3). Our goal was to develop appropriate conditions for the analysis of DNA adducts of NPYR formed in vivo. Products of the alpha-acetoxyNPYR-dGuo reactions were analyzed directly by HPLC or after treatment of the reaction mixtures with NaBH3CN. Products of the alpha-acetoxyNPYR-DNA reactions were released by enzymatic or neutral thermal hydrolysis of the DNA, then analyzed by HPLC. Alternatively, the DNA was treated with NaBH3CN prior to hydrolysis and HPLC analysis. The reactions of alpha-acetoxyNPYR with dGuo and DNA were complex. We have identified 13 products of the dGuo reaction-6 of these were characterized in this reaction for the first time. They were four diastereomers of N2-(3-hydroxybutylidene)dGuo (20, 21), 7-(N-nitrosopyrrolidin-2-yl)Gua (2), and 2-(2-hydroxypyrrolidin-1-yl)deoxyinosine (12). Adducts 20 and 21 were identified by comparison to standards produced in the reaction of 3-hydroxybutanal with dGuo. Adduct 2 was identified by its spectral properties while adduct 12 was characterized by comparison to an independently synthesized standard. With the exception of adduct 2, all products of the dGuo reactions were also observed in the DNA reactions. The major product in both the dGuo and DNA reactions was N2-(tetrahydrofuran-2-yl)dGuo (10), consistent with previous studies. Several other previously identified adducts were also observed in this study. HPLC analysis of reaction mixtures treated with NaBH3CN provided improved conditions for adduct identification, which should be useful for in vivo studies of DNA adduct formation by NPYR.

Role of Hexacoordinated Silicon Intermediates in the Hydrolysis and Racemization Reactions of Silyl Halides

Potential energy surfaces for systems consisting of SiH3F and SiH3Cl molecules with addition of two water molecules (as a model for neutral hydrolysis), with one water and one ammonia molecule (base-catalyzed hydrolysis), and with two ammonia molecules (racemization) were investigated by the B3LYP and MP2 methods with 6-31G(d,p) and 6-311+G(d,p) basis sets. It was shown that in addition to global energy minima corresponding to loosely bound complexes with SiO and SiN separations exceeding 2.5 Å, there exist the stationary points for tightly bound, low-entropy complexes with SiO and SiN bonds of length ca. 2.0 Å. Such complexes were predicted earlier by the analysis of experimental data on nucleophile-assisted hydrolysis and racemization. For SiH3F structures of these complexes are close to octahedral with NH3 or H2O in axial positions, while those for silyl chloride are closer to trigonal bipyramidal zwitterions formed by the SiH3 cation with two nucleophiles and the Cl anion separated from Si by ca. 3 Å. The barriers separating these local minima from collapsing into the global minima (with inversion of configuration) are ca. 10 kcal/mol in systems with two ammonia molecules, However, with substitution of ammonia by water molecules these barriers tend to disappear, and shallow minima at the top of the barrier for inversion of configuration develop into transition states. This tendency is more pronounced for silyl chloride. The barrier for this channel providing inversion of configuration for the SiH3Cl + 2H2O system becomes lower than the competing channel leading to the hydrolysis products. This is in keeping with the observed preference of the inversion channel for the neutral hydrolysis of chlorosilanes.

Kinetic Investigation on the Hydrolysis of Aryl(fluoro)(phenyl)-λ6-sulfanenitriles

Abstract A kinetic investigation on the hydrolysis of aryl(fluoro)(phenyl)-λ6-sulfanenitriles was carried out in some aqueous and mixed aqueous-organic solutions. The pH-rate profiles showed that the hydrolysis consists of pH-independent, acid-catalyzed and base-catalyzed reactions. The neutral hydrolysis of fluoro-λ6-sulfanenitriles was found to proceed via an SN1 or an S-nitrilosulfonium cation-like transition state, which is characterized by a large negative Hammett ρ-value (ρ = −1.76 in water; −1.85 in CH3CN/H2O(1/4, v/v); −2.35 in TFE/H2O (1/1, v/v)), relatively large m-values (ca. 0.83 for fluoro(diphenyl)-λ6-sulfanenitrile; ca. 0.82 for fluoro(p-nitrophenyl)(phenyl)-λ6-sulfanenitrile against the solvent ionizing power YOTs-values in acetonitrile–water), a common ion effect in TFE/H2O, and a small salt effect. The large negative activation entropies (−60 – −101 J K−1 mol−1) were presumed to be due to strong solvation of F− with H2O in the reaction systems. The ease of ion dissociation of the S–F bond was examined by a theoretical calculation in a DFT method, to show that the SN1-like transition state is caused by a facile tendency of dissociation of the S–F bond of fluoro-λ6-sulfanenitriles. The acid-catalyzed hydrolysis was found to proceed via a more cation-like transition state involving a concerted proton transfer to the fluorine atom and breaking of the sulfur-fluorine bond in the λ6-sulfanenitrile. The alkaline hydrolysis probably takes place via an SN2 mechanism.

Short- and long-term effects of atorvastatin, lovastatin and simvastatin on the cellular metabolism of cholesteryl esters and VLDL secretion in rat hepatocytes

The short- and long-term in vitro effects of the hydroxymethylglutaryl-CoA reductase inhibitor atorvastatin, compared with lovastatin and simvastatin on VLDL secretion, and on the formation and the neutral and acid lysosomal hydrolysis of cholesteryl esters was investigated in rat liver hepatocytes maintained in suspension (2 or 4 h) or cultured in monolayers (24 h). All statins time-dependently reduced [ 14C]oleate incorporation into cholesteryl esters, but when exogenous cholesterol was added only atorvastatin caused an immediate transient decrease in hepatocyte ACAT activity. Activity of the lysosomal, microsomal and cytosolic CEH isoforms was unaffected by the hepatocyte treatments. Statins reduced free and esterified cholesterol mass in hepatocyte microsomes after 2 h, and this was followed by a modest decline in VLDL cholesteryl esters, whilst secretion of VLDL apoB and triglycerides was unaltered. However, after 24 h of treatment, statins caused generalized 20–40% decreases in the secretion of VLDL apoB, cholesterol and triglycerides, with the reduction in apoB48 secretion being significantly superior to that caused in apoB100. The mean diameter of secreted VLDL was not modified by either duration or drug treatment. Additional studies with subcellular fractions demonstrated that statins have a direct selective effect on the enzymes governing the cholesterol-cholesteryl ester cycle, with the exception of the microsomal CEH. Atorvastatin, lovastatin and simvastatin inhibited ACAT activity in microsomes by 50% at doses of 250, 100 and 50 μM, respectively. The cytosolic CEH elicited a biphasic profile of activity with activations up to 100 μM statin and inhibitions above 250 μM, and the lysosomal CEH was only inhibited by atorvastatin at a dose of 100 μM or more. We conclude that a prolonged, but not a short, limited availability of hepatocyte cholesterol derived from the endogenous synthesis reduces VLDL secretion, and that reactivity of statins at the cellular level are more similar than reactivity at the subcellular level as regards the cholesterol-cholesteryl ester cycle.