Epimerization Kinetics Research Articles

Effects of peripheral substituents on epimerization kinetics of formylated chlorophylls

C132-[Formula: see text]-epimers of chlorophyll (Chl) molecules are important cofactors in the photosystem I reaction centers in oxygenic photosynthetic organisms; however, their production mechanism is still unclear. The reaction properties of Chl epimerization are helpful for a better understanding of the molecular mechanism of the in vivo formation of Chl C132-[Formula: see text]-epimers. We report herein the kinetic properties of the epimerization of formylated Chl molecules, Chl [Formula: see text] and Chl [Formula: see text], by use of triethylamine. Both Chl [Formula: see text] and Chl [Formula: see text] performed faster epimerization kinetics than Chl [Formula: see text], indicating that the electron-withdrawing ability of the formyl groups directly linked to the chlorin macrocycle is responsible for acceleration of the epimerization. Comparing the rate constants of the two mono-formylated Chl molecules indicated that the epimerization of Chl [Formula: see text] was faster than that of Chl [Formula: see text]. This difference is rationalized by invoking a combination of the inductive effects of the C3- and C7-substituents in Chls; the sums of Hammett [Formula: see text] parameters of the C3- and C7-substituents exhibited high correlations with the epimerization rate constants of Chls [Formula: see text], [Formula: see text], and [Formula: see text].

Structural effects on epimerization of bacteriochlorophyll a and chlorophyll a revealed using 3-acetyl chlorophyll a

Chlorophyll (Chl) and bacteriochlorophyll (BChl) pigments, which are crucial cyclic tetrapyrroles in photosynthesis, generally have a chiral center in their exo-cyclic five-membered E-ring. Although [Formula: see text]-epimers (primed-type) of (B)Chl pigments are rarely present in photosynthetic organisms, they play key roles in photosynthetic reaction center complexes. The epimerization mechanism of (B)Chl pigments in vivo has not been unraveled. The structural effects on the physicochemical properties of (B)Chl epimerization reactions provide useful information to tackle this question. We analyzed epimerization of three pigments, BChl [Formula: see text], Chl [Formula: see text], and 3-acetyl Chl [Formula: see text], to elucidate the structural factors that are responsible for epimerization reactions. We compared the epimerization kinetics of the three pigments and concluded that the bacteriochlorin skeleton (7,8,17,18-tetrahydroporphyrin) significantly retarded the epimerization kinetics. Thus, BChl [Formula: see text] exhibited slower epimerization kinetics than Chl [Formula: see text] in spite of the presence of the electron-withdrawing 3-acetyl group that accelerates epimerization. In contrast to the large structural effects of (B)Chl molecules on epimerization kinetics, the thermodynamic properties at equilibrium in the epimerization of the three pigments were barely influenced by their molecular structures. This study also demonstrates that a semi-synthetic pigment, 3-acetyl Chl [Formula: see text], is appropriate for comparative analyses of the structural effects of BChl [Formula: see text] and Chl [Formula: see text] on their physicochemical properties.

Stereochemistry of the Menthyl Grignard Reagent: Generation, Composition, Dynamics, and Reactions with Electrophiles.

Menthyl Grignard reagent 1 from either menthyl chloride (2) or neomenthyl chloride (3) consists of menthylmagnesium chloride (1a), neomenthylmagnesium chloride (1b), trans- p-menthane (4), 2-menthene (8), 3-menthene (9), and Wurtz coupling products including symmetrical bimenthyl 13. The diastereomeric ratio 1a/1b was determined in situ by 13C NMR or after D2O quenching by 2H NMR analysis. Hydrolysis of the C-Mg bond proceeds with retention of configuration at C-1. The kinetic ratio 1a/1b from Grignard reagent generation (dr 59:41 at 50 °C in THF) is close to the thermodynamic ratio (56:44 at 50 °C in THF). Carboxylation of 1 at -78 °C separates diastereomers 1a/b to give the anion of menthanecarboxylic acid (19) from 1a, which combines with unreactive 1b to give neomenthylmagnesium menthanecarboxylate (1bI). The kinetics of epimerization for the menthyl/neomenthylmagnesium system was analyzed (Δ H⧧ = 98.5 kJ/mol, Δ S⧧ = -113 J/mol·K for 1bI → 1aI). Reactions of 1 with phosphorus electrophiles proceed stereoconvergently at C-1 of 1a/b to give predominantly menthyl-configured substitution products: PCl3 and 2 equiv of 1 give Men2PCl (6), which hydrolyzes to dimenthylphosphine P-oxide (7), whereas Ph2PCl with 1 equiv of 1 gave P-menthyldiphenylphosphine oxide (27) after workup in air.

Kinetic and Thermodynamic Control of Nitrile Dissociation in the Complexes (RFe,RC)/(SFe,RC)-[CpFe(Prophos)NCR]X (X = I, PF6) by the Inductive Effect

The chiral-at-metal complexes (RFe,RC)/(SFe,RC)-[CpFe(Prophos)NCR]X (X = I, PF6; R = Et, Ph, p-substituted Ph) were prepared, and the diastereomers were separated by fractional crystallization. Eight diastereomerically pure complexes (SFe,RC)-[CpFe(Prophos)NCR]X could be characterized by X-ray crystallography. The kinetics of epimerization with respect to the labile Fe-configuration in CDCl3 at ambient temperatures was measured for the EtCN, PhCN, and (p-C6H4NMe2) complexes. The half-lives of 162 and 760 min of the first-order reactions of (SFe,RC)-[CpFe(Prophos)NCPh]PF6 and (SFe,RC)-[CpFe(Prophos)NC(p-C6H4NMe2)]PF6 at 293 K demonstrate the importance of the inductive effect in the rate-determining cleavage of the Fe–NCR bond. The diastereomer ratios of 5:95 to 10:90 at equilibrium under thermodynamic control were strongly in favor of the (SFe,RC)-[CpFe(Prophos)NCR]X diastereomers. In ligand exchange reaction reactions, (RFe,RC)/(SFe,RC) diastereomer ratios of up to 35:65 were observed under kinetic control.

Problems and Pitfalls in the Analysis of Amygdalin and Its Epimer.

α-[(6-O-β-d-Glucopyranosyl-β-d-glucopyranosyl)oxy]-(αR)-benzeneacetonitrile, or R-amygdalin, is the most common cyanogenic glycoside found in seeds and kernels of the Rosaceae family and other plant genera such as Passiflora. Many commercially important seeds are analyzed for amygdalin content. In "alternative medicine", amygdalin has been sold as a treatment for cancer for several decades without any rigorous scientific support for its efficacy. We have found that there are some inconsistencies and possible problems in the published analytical chemistry of amygdalin. It is shown that some analytical approaches do not account for the presence of the S-isomer; therefore, a fast reliable method was developed using a chiral stationary phase and HPLC. This approach allows "real-time" monitoring and complete and highly efficient separations. It is found that the S-amygdalin continuously forms in aqueous solutions. A striking result is that the conversion of amygdalin is glassware dependent. "Clean" vials from various vendors can show drastically different reaction rates of the conversion to the isomer (S-amygdalin, also called neo-amygdalin). The epimerization kinetics are dependent on the solvent, temperature, pH, and the nature of the container. For example, epimerization in water was complete in <15 min in a new glass vial taken from the box, whereas it can take >1 h in specially cleaned glassware. Conversely, epimerization can be significantly delayed at high temperature if high-density polyethylene is used as the container. Hence, inert plastic containers are recommended for storage of aqueous amygdalin solutions. Commercial preparations of R-amygdalin actually contain greater quantities of S-amygdalin and ∼ 5% of other degradation products.

Stability of sugar solutions: a novel study of the epimerization kinetics of lactose in water.

This article reports on the stereochemical aspects of the chemical stability of lactose solutions stored between 25 and 60 °C. The lactose used for the preparation of the aqueous solutions was α-lactose monohydrate with an anomer purity of 96% α and 4% β based on the supplied certificate of analysis (using a GC analytical protocol), which was further confirmed here by nuclear magnetic resonance (NMR) analysis. Aliquots of lactose solutions were collected at different time points after the solutions were prepared and freeze-dried to remove water and halt epimerization for subsequent analysis by NMR. Epimerization was also monitored by polarimetry and infrared spectroscopy using a specially adapted Fourier transform infrared attenuated total reflectance (FTIR-ATR) method. Hydrolysis was analyzed by ion chromatography. The three different analytical approaches unambiguously showed that the epimerization of lactose in aqueous solution follows first order reversible kinetics between 25 to 60 °C. The overall rate constant was 4.4 × 10(-4) s(-1) ± 0.9 (± standard deviation (SD)) at 25 °C. The forward rate constant was 1.6 times greater than the reverse rate constant, leading to an equilibrium constant of 1.6 ± 0.1 (±SD) at 25 °C. The rate of epimerization for lactose increased with temperature and an Arrhenius plot yielded an activation energy of +52.3 kJ/mol supporting the hypothesis that the mechanism of lactose epimerization involves the formation of extremely short-lived intermediate structures. The main mechanism affecting lactose stability is epimerization, as no permanent hydrolysis or chemical degradation was observed. When preparing aqueous solutions of lactose, immediate storage in an ice bath at 0 °C will allow approximately 3 min (180 s) of analysis time before the anomeric ratio alters significantly (greater than 1%) from the solid state composition of the starting material. In contrast a controlled anomeric composition (~38% α and ~62% β) will be achieved if an aqueous solution is left to equilibrate for over 4 h at 25 °C, while increasing the temperature up to 60 °C rapidly reduces the required equilibration time.

Capillary electrophoretic study of the degradation pathways and kinetics of the aspartyl model tetrapeptide Gly-Phe-Asp-GlyOH in alkaline solution

The aim of the present study was the investigation of the isomerization and epimerization kinetics of the aspartyl tetrapeptide Gly-Phe-Asp-GlyOH at alkaline conditions. Incubations of the model tetrapeptide in sodium borate buffer, pH 10 and ionic strength 0.2M, at 25°C and 80°C were analyzed by a validated CE–UV assay and fitted according to a pharmacokinetic model. CE–ESI-MS was used for peptide identification. Enantiomerization and isomerization of the aspartyl residue of the model tetrapeptide was observed under all experimental conditions applied. Differences in the velocity and the ratios of the rates of the degradation reactions indicated different effects of temperature on the individual reactions. At 80°C, a rapid formation of β-Asp and d-Asp containing isomers from Gly-l-Phe-α-l-Asp-GlyOH was monitored. Rate constants of the hydrolysis of the succinimide (Asu) intermediate generally exceeded the formation of the intermediate from α/β-Asp peptides. A higher rate constant was observed for the enantiomerization from l-configured Asu compared to d-Asu. At 25°C, epimerization and isomerization equilibrium was not reached within 5208h. Compared to 80°C different ratios of the individual reaction rates were noted. Moreover, inversion of the sequence of the first 2 amino acids was noted as a minor side reaction at 80°C.

Isolation and epimerization kinetics of the first diastereoisomer of an inherently chiral uranyl-salophen complex.

The first diastereoisomeric mixture of an inherently chiral uranyl-salophen complex was prepared using (S)-naproxen as a chiral derivatizing agent. Slow crystallization from diisopropyl ether-chloroform afforded one pure diastereoisomer in 45% yield. Kinetic studies allowed the determination of the epimerization rate. [reaction--see text]

Catalytic propene polymerization: determination of propagation, termination, and epimerization kinetics by direct NMR observation of the (EBI)Zr(MeB(C6F5)3)propenyl catalyst species.

Treatment of (EBI)ZrMe2 with B(C6F5)3 and 100 equiv of 1-hexene in toluene-d8 at -40 degrees C for 1 h, followed by addition of >5 equiv of propene, generates a living polypropene catalyst (3) with a polyhexene "tail". Upon further addition of propene, speciation of the catalyst and propagation kinetics are measured directly by NMR, yielding a propagation rate law that is first order in [propene] and [living catalyst] with a rate constant of 2.6 M-1 s-1 at -40 degrees C and the activation parameters DeltaH = 3.4(0.2) kcal/mol and DeltaS = -42(2) cal/(mol K). In the absence of propene, elimination of vinylidene-terminated polymer is observed with a first-order rate constant of 3.3 (0.5) x 10-5 s-1 at -40 degrees C and DeltaH = 12.9(1.4) kcal/mol and DeltaS = -23(5) cal/(mol K). Use of 1-13C-propene and 1,1-2H-2,3-13C-propene and 1H, 19F, and 13C NMR spectroscopy provide rigorous characterization of the living catalyst and enable the first direct observation of both 1,3-isomerization and chain-end epimerization processes at a metallocene catalyst. Isomerization and epimerization occur with rates that are similar to that of vinylidene termination and are consistent with previous mechanistic hypotheses featuring isomerization via a tertiary alkyl intermediate and switching between enantiofaces of the coordinated alkene.

Aminostratigraphy of Pliocene-Pleistocene high-sea-level deposits, Nome coastal plain and adjacent nearshore area, Alaska

Amino acid epimerization ratios (aIle/Ile) measured in 295 fossil molluscan shells of 3 genera provide a basis to evaluate the number and relative timing of high-sea-level events represented by deposits blanketing the Nome coastal plain and adjacent nearshore area, northwestern Alaska. Frequency-distribution analysis, along with a new approach that relies on the ranked-data distribution, was used to identify clusters (aminozones) in the aIle/Ile data, each of which presumably represents a discrete period of marine inundation of the study area. Six periods of high relative sea level were distinguished; some are recognized only by redeposited shells rather than in situ bio- or lithostratigraphic units. The oldest period is represented by shells recovered from the deepest sections of two offshore boreholes; aIle/Ile ratios in these shells (1.0) are much higher than in any found onshore and probably date to the late Miocene/early Pliocene. The oldest aminozone lies below nonfossiliferous sediments, which, in turn, are overlain by glacigenic and marine deposits containing largely fragmented shells with aIle/Ile ratios ranging from 0.35 to 0.65. This range coincides with aIle/Ile ratios from various onshore deposits previously ascribed to the middle Pliocene (∼3 m.y.) Beringian transgression. Ratios in this range can be subdivided into three evenly spaced aminozones, each of which may represent multiple, short-duration (10 4 yr) high-sea stands separated by a longer-period (>10 5 yr) sea-level oscillation. On the basis of a new empirical model of parabolic epimerization kinetics and an assumed age of 3.2 m.y. for the oldest Beringian aminozone (the approximate age of the initial submergence of Bering Strait), the estimated length of time represented by the three Beringian aminozones is between 0.5 and 1.7 m.y. The youngest Beringian highstand was followed in the late Pliocene or early Pleistocene by a lengthy period of nonmarine deposition during which local valley glaciers advanced onto the coastal plain at least once. Relative sea level apparently did not again surpass that of today until the middle Pleistocene Anvilian transgression, the oldest higher-than-present stand of the Pleistocene, yet considerably younger than previously thought. Glaciers overran the Nome coastal plain at least once following the Anvilian transgression, incorporating abundant shells into their drift. The drift is notched by a shoreline formed during the Pelukian transgression of the last interglaciation. Although well represented onshore, no Pelukian deposits have been found offshore.

Renin inhibitors containing esters at the P2-position. Oral activity in a derivative of methyl aminomalonate

A series of renin inhibitors containing ester side chains at the P2 subsite are potent inhibitors of primate renin. Derivatives containing the diol isostere (ACDMH) at P1-P1' were the most potent inhibitors. Moderate selectivity for renin was observed relative to the closely related aspartic proteinase cathepsin D. The prototype compound, 4 (PD 132002), inhibited pepsin only weakly. In both high-renin normotensive and high-renin renal hypertensive monkeys, 4 produced substantial reductions in blood pressure after oral administration of 30 mg/kg. The maximum drop in blood pressure observed (24 +/- 4 mmHg) in the renal hypertensive monkey model was comparable to the drop produced by an intravenous infusion of saralasin at a maximally effective dose. Both the magnitude and duration of the oral antihypertensive effect of 4 is greater than that produced by enalkiren, CGP-38560, or CP-80794 by direct comparison in the same hypertensive monkey model. The malonate ester derivatives were prepared as ca. 65:35 mixtures of epimers. The kinetics of epimerization of 4 were investigated in detail, and it was shown to equilibrate rapidly at physiological pH (t1/2 less than 2 min). Fractional crystallization was employed to obtain the individual diastereomers in greater than 98% purity, which were indistinguishable in terms of their activity in vitro or in vivo, presumably due to rapid epimerization under the testing conditions.

Epimerization kinetics of moxalactam in frozen urine and plasma samples.

The epimerization of moxalactam (LMOX) in frozen urine and plasma samples was studied during long-term storage. The R/S ratio at equilibrium [(R/S)eq] at -10 degrees C was similar in urine and in rat and human plasma ultrafiltrate but differed from that in water. The (R/S)eq values in human plasma and its ultrafiltrate differed slightly, while they were the same in rat plasma and in its ultrafiltrate. The difference for the human plasma and ultrafiltrate may result from differences in plasma protein binding between R- and S-epimers in the liquid region of the frozen plasma. The change of R/S ratio in frozen human plasma continued below the collapse temperature of LMOX aqueous solution, where the liquid region appeared still to exist as determined by NMR measurement. Consequently, the biological LMOX samples should be preserved at or below -70 degrees C to prevent changes in the R/S ratio.

Epimerization kinetics of moxalactam in frozen solution.

The epimerization rate constants of R- and S-epimers of moxalactam (LMOX) in a frozen aqueous solution decreased as the temperature decreased. The reaction proceeded in the unfrozen region remaining in the frozen solution, without being affected by the ice. The reaction stopped completely below the collapse temperature of the LMOX aqueous solution. The ratio of R- and S-epimers at equilibrium, which was equal to the ratio of the epimerization rate constant, increased as the temperature decreased. This change in the ratio at equilibrium could be ascribed to the difference in the activation energy between the two epimers.

Dehydration and Epimerization of 7-Thiaprostaglandin E1 Analogues

The kinetics of epimerization and dehydration of 7-thiapros-taglandin E1 (7-S-PGE1)analogues in various solvent systems were examined using HPLC. The epimerization at the C-8 position was rapid and resulted in a considerable amount of the 8-epimer (14–35%) at equilibrium. The dehydration was also rapid compared with that of the natural prostaglandin E1 (PGE1). The lability may be attributed to an effect of the sulfur atom substituted for the C-7 methylene.

Epimerization Kinetics of Moxalactam, Its Derivatives, and Carbenicillin in Aqueous Solution

The mechanism of the epimerization of moxalactam was studied by measuring the rate of epimerization after deuteration of the C-7 side-chain chiral carbon, introduction of different substituents on the side chain, and variation of the ring system. Deuteration slowed the epimerization rate considerably. The rate was also influenced by the choice of the ring system and the substituent on the C-7 side-chain chiral carbon. When the penicillin ring system with the 2-carboxy-2-phenyl-acetamide was studied, the epimerization rate decreased indicating that the same ring system needed to be used throughout the epimerization studies. Thus, experiments were conducted with different substituents replacing the phenolic group at the C-7 side-chain chiral carbon of moxalactam. The epimerization rate decreased in the substituent order thienyl, phenyl, 4-hydroxyphenyl, the ionized form of 4-hydroxyphenyl, and ethyl. These results showed that dehydrogenation of the chiral carbon seems to be the rate-determining step and that the stronger the electron-donating effect of the substituent, the slower the epimerization rate becomes.

Degradation and Epimerization Kinetics of Moxalactam in Aqueous Solution

The kinetics of epimerization and degradation of moxalactam in aqueous solution was investigated by HPLC. The pH-rate profiles of the degradation and epimerization were determined separately over the pH range of 1.0–11.5 at 37°C and constant ionic strength 0.5. The degradation and simultaneous epimerization were followed by measuring both of the residual R- and S-epimers of moxalactam and were found to follow pseudo-first-order kinetics. The degradation was subjected to hydrogen ion and hydroxide ion catalyses and influenced by the dissociation of the side chain phenolic group. The epimerization rates were influenced significantly in the acidic region by the dissociation of the side chain carboxylic acid group and in the basic region by hydroxide ion catalysis. The pH-degradation rate profile of moxalactam showed a minimum degradation rate constant between pH 4.0 and 6.0. The pH-epimerization rate profiles of moxalactam showed minimum epimerization rate constants at pH 7.0. The epimerization rate constants of the R- and S-epimers were not very different.

Acid-catalyzed Hydrolyses of Bridged Bi- and Tricyclic Compounds. XXII. Kinetics of Epimerization and Hydration of exo- and endo-5-Acetyl-2-norbornenes and Hydration of 3-Acetylnortricyclane.

Acid-catalyzed Hydrolyses of Bridged Bi- and Tricyclic Compounds. XXII. Kinetics of Epimerization and Hydration of exo- and endo-5-Acetyl-2-norbornenes and Hydration of 3-Acetylnortricyclane.

Kinetics of epimerization of (+)-catechin and its rearrangement to catechinic acid

Kinetics of epimerization of (+)-catechin and its rearrangement to catechinic acid

Hydrolysis and epimerization kinetics of pilocarpine in basic aqueous solution as determined by HPLC

A high-performance liquid chromatographic method is described which allows the simultaneous determination of pilocarpine and the products of its degradation, isopilocarpine, pilocarpic acid and isopilocarpic acid. Using this method the degradation pattern of pilocarpine in basic aqueous solution was determined. The epimerization of pilocarpine to isopilocarpine was found to be a reversible reaction although the equilibrium is strong in favor of isopilocarpine. Isopilocarpine was readily detected during the overall degradation of pilocarpine and was found to possess the same stability as its diastereoisomer. The relative importance of epimerization to hydrolysis of pilocarpine increased with increased temperature, ranging from 12% at 18°C to 20% at 66°C.

Kinetics of epimerization of 15(R)-methylprostaglandin E2 and of 15(S)-methylprostaglandin E2 as a function of pH and temperature in aqueous solution

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetics of epimerization of 15(R)-methylprostaglandin E2 and of 15(S)-methylprostaglandin E2 as a function of pH and temperature in aqueous solutionMargaret V. Merritt and George E. BronsonCite this: J. Am. Chem. Soc. 1978, 100, 6, 1891–1895Publication Date (Print):March 1, 1978Publication History Published online1 May 2002Published inissue 1 March 1978https://doi.org/10.1021/ja00474a040RIGHTS & PERMISSIONSArticle Views62Altmetric-Citations16LEARN 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 (585 KB) Get e-Alerts Get e-Alerts