Initial Ee Research Articles

Deracemization of sodium chlorate by hydrodynamic attrition of Taylor vortex flow

We investigated the deracemization of sodium chlorate in the unique hydrodynamic environment of Taylor vortex flow (TVF) in Couette-Taylor (CT) crystallizer. Our findings revealed a remarkable enhancement in the deracemization due to the effective hydrodynamic attrition of crystals, as compared to conventional mixing tank (MT) crystallizers utilizing the turbulent eddy flow (TEF). So, the deracemization of initial ee = 0 % in the CT crystallizer was significantly enhanced as increasing the rotation speed whereas the deracemization in the MT crystallizer occurred seldom with increase of agitation speed. Using the sparsely soluble solvent, it was demonstrated the TVF was much more effective for the hydrodynamic attrition of the crystals than the TEF. The deracemization depended not only on the flow intensity (viscous energy dissipation) but also the flow pattern. So, the TVF always produced the higher deracemization than the TEF at the same viscous energy dissipation. Also, the flow intensity and flow pattern significantly dictated the crystal agglomeration of homo-chiral (L-form and D-form) and hetero-chiral (L/D-form) forms during the deracemization. Our findings demonstrated the potential of the periodic TVF in the deracemization. The hydrodynamic attrition effect in the CT crystallizer provides a means to enhance enantiomeric purity and offers insights into the design of novel deracemization systems.

High-throughput determination of enantiopurity in atroposelective synthesis of aryl triazoles.

Atropisomeric scaffolds are a common design element found in pharmaceuticals, many deriving from an N-C axis of chirality. The handedness associated with atropisomeric drugs is oftentimes crucial for their efficacy and/or safety. With the increased use of high-throughput screening (HTS) for drug discovery, the need for rapid enantiomeric excess (ee) analysis is needed to keep up with the fast workflow. Here, we describe a circular dichroism (CD) based assay that could be applied to the ee determination of N-C axially chiral triazole derivatives. Analytical samples for CD were prepared from crude mixtures by three sequential steps: liquid-liquid extraction (LLE), a wash-elute, and complexation with Cu(ii) triflate. The initial ee measurement of five samples of atropisomer 2 was conducted by the use of a CD spectropolarimeter with a 6-position cell changer, resulting in errors of less than 1% ee. High-throughput ee determination was performed on a CD plate reader using a 96-well plate. A total of 28 atropisomeric samples (14 for 2 and 14 for 3) were screened for ee. The CD readings were completed in 60 seconds with average absolute errors of ±7.2% and 5.7% ee for 2 and 3, respectively.

Collection and Characterization by Mass Spectrometry of the Neutral Serine Octamer Generated upon Sublimation.

Serine forms neutral octameric clusters during sublimation, as demonstrated by electrostatically deflecting thermally ionized serine species from the sublimate, then gently ionizing the remaining neutrals for examination by mass spectrometry (MS). The MS results demonstrate a strong homochiral preference in the neutral octamer (measured after its gentle ionization), while the smaller serine clusters are achiral. In the initial stages of its sublimation, nonracemic solid serine generates a neutral serine monomer as the principal species in the vapor phase, with a significant enantiomeric enrichment relative to the solid. The serine monomer, when the flux is sufficient, assembles into the octamer, which displays a much higher chiral purity than the monomer. The serine octamer is separated from other neutral clusters in the sublimate by a new method based on the different distances that the clusters travel in an inert gas stream before they condense in a cooled collector. The deposited octamer is subsequently dissolved, and the solution is investigated by MS. The spectrum confirms that the collected serine octamer has undergone chiral enrichment relative to the starting solid used in the sublimation. The chiral enrichment observed in going from the serine monomer to octamer can be accommodated using a chemical model, grounded on the homochiral preference of the neutral serine octamer. Using the enantiomeric excess (ee %) of the vapor-phase monomer as the input, the model output matches the experimental octamer ee % when subliming solid serine with various initial ee % values.

Kinetic relationship in parallel autocatalytic amplifications of pyridyl alkanol and chiral trigger pyrimidyl alkanol.

Experimental and kinetic analysis of a chemical system combines autocatalytic amplification of 2-alkynyl-5-pyrimidyl alkanol 2 and 6-alkynyl-3-pyridyl akanol 4 in which 2 acts as a chiral trigger and 4 being the subsequent autocatalyst. Starting from a very low initial ee, both alkanols are produced with high enantiopurity in one single cycle. This provides insight into a dual nonlinear amplification of chirality observed with amplifying trigger 2 and accelerated amplification of autocatalyst 4. These kinetic studies reveal a five-fold magnitude superior amplification rates of 4 associated with trigger's enantiopurity at the outset.

Asymmetric Autocatalysis as a Relay for Remote Amplification of Chirality of Target Molecules Used as Triggers.

Nearly racemic target molecules are enantiomerically enriched through an asymmetric autocatalytic relay for a remote amplification of chirality. Target alkynols with very low initial ee act as chiral triggers for asymmetric amplification of the Soai autocatalyst, which in turn enables the formation of the same alkynols with greater enantiomeric purity. Additionally, the stereochemical correlation between the trigger/target and autocatalyst molecules is discussed.

The effects of lyophilization on the physico-chemical stability of sirolimus liposomes.

The major limitation in the widespread use of liposome drug delivery system is its instability. Lyophilization is a promising approach to ensure the long-term stability of liposomes. The aim of this study was to prepare sirolimus-loaded liposomes, study their stability and investigate the effect of lyophilization either in the presence or in the absence of lyoprotectant on liposome properties. Two types of multi-lamellar liposomes, conventional and fusogenic, containing sirolimus were prepared by modified thin film hydration method with different ratio of dipalmitoylphosphatidylcholine (DPPC), cholesterol and dioleoylphosphoethanolamine (DOPE), and were lyophilized with or without dextrose as lyoprotectant. Chemical stability investigation was performed at 4°C and 25°C until 6 months using a validated HPLC method. Physical stability was studied with determination of particle size (PS) and encapsulation efficiency (EE %) of formulations through 6 months. Chemical stability test at 4°C and 25°C until 6 months showed that drug content of liposomes decreased 8.4% and 20.2% respectively. Initial mean EE % and PS were 72.8 % and 582 nm respectively. After 6 months mean EE % for suspended form, lyophilized without lyoprotectant and lyophilized with lyoprotectant were 54.8 %, 62.3% and 67.1 % at 4°C and 48.2%, 60.4 % and 66.8 % at 25°C respectively. Corresponding data for mean PS were 8229 nm, 2397 nm and 688nm at 4°C and 9362 nm, 1944 nm and 737 nm at 25°C respectively. It is concluded that lyophilization with and without dextrose could increase shelf life of liposome and dextrose has lyoprotectant effect that stabilized liposomes in the lyophilization process.

Enantioselective resolution of chiral drugs using BSA functionalized magnetic nanoparticles

Bovine serum albumin (BSA) anchored on the surface of magnetic Fe3O4 nanoparticles (MNPs) were prepared using electrostatic adsorption and studied as a new magnetically chiral selector for the separation of chiral drug enantiomers. It is indicated that the immobilized BSA molecules on the magnetic nanoparticles using electrostatic adsorption retain their stereoselective recognition with site II-binding drug ibuprofen at pH 7.0 and site I-binding drug ofloxacin at pH 9.0, with a optimal loading of 467mg BSA per gram of MNPs. For racemic ibuprofen and ofloxacin, single-stage adsorption gives an enantiomeric excess of 13% and 14%, and the multi-stage operation enhances the chiral performance providing the ee value of 54% and 39% respectively. As increasing the initial ee of enantiomeric mixtures, Δee levels of 50%, 35% and 16% for stronger binder ibuprofen, as well as 31%, 17% and 13% for weaker binder ofloxacin are achieved under the same operational conditions. Depending upon the eutectic point of racemic compound, a hybrid process involving the enrichment of one enantiomer using BSA–PDDA–MNPs followed by subsequent crystallization is proposed to obtain the enantiomer with higher optical purity.

Asymmetric Synthesis of (S)-3-Amino-4-methoxy-butan-1-ol by Way of Reductive Amination

A new synthesis of (S)-3-amino-4-methoxy-butan-1-ol is reported. The synthesis is based on the preparation of the primary, nonprotected enamine of the commercially available β-keto ester methyl 4-methoxy-3-oxo-butanoate and asymmetric catalytic enamine hydrogenation using a Ru-MeOBIPHEP catalyst. Alternatively, the process is performed by asymmetric catalytic reductive amination of the β-keto ester with ammonium acetate and hydrogen using a similar Ru catalyst. Both process versions provided initial ee values of 97−98% which were upgraded to ≥99% by product crystallization. Ester to alcohol conversion was best accomplished by LiBH4 reduction after transitory Boc protection of the amino group.

Kinetic degradation model and estrogenicity changes of EE 2 (17α-ethinylestradiol) in aqueous solution by UV and UV/H 2O 2 technology

The photochemical degradation and estrogenicity removal of 17α-ethinylestradiol in aqueous solutions was investigated via ultraviolet (UV) photolysis and UV/H 2O 2 process with a low-pressure UV lamp. The results indicated that the kinetics of both oxidation processes well fitted the pseudo-first-order kinetics. EE 2 can be partially removed by UV radiation alone with kinetic constants increasing from 0.0054 to 0.2753 min −1 with the UV intensity increase. The EE 2 degradation rate enhanced from 0.0364 to 0.0684 min −1 when H 2O 2 was combined with the photolysis process (UV/H 2O 2), even though EE 2 was not oxidized when same amounts of H 2O 2 existed in the aqueous solutions. The kinetic parameters of pseudo-first-order kinetics showed positive correlation to UV intensity and also H 2O 2 concentration, however negative to the initial EE 2 concentration. A regression model was developed for pseudo-first-order rate constant as a function of the UV intensity, H 2O 2 concentration and initial EE 2 concentration, which could be used to estimate the EE 2 degradation rate at various operational conditions. The yeast estrogen screen (YES) was employed to evaluate the estrogenicity of photolytic water samples. Results showed that more than 95% of the estrogenicity was removed after 40 min irradiation and the parent compound EE 2 was mainly responsible for the observed estrogenicity.

Adsorption behavior of EE2 (17α-ethinylestradiol) onto the inactivated sewage sludge: Kinetics, thermodynamics and influence factors

The adsorption behavior of 17 alpha-ethinylestradiol (EE(2)) onto inactivated sludge was investigated to assess the function of adsorption on EE(2) removal in activated sludge system. The adsorption equilibrium of EE(2) can be achieved in 5.0 h at the research temperature and the adsorption process could be well described by pseudo-second-order model. The equilibrium data at different temperatures were fitted by a linear regression. The thermodynamics analysis revealed that EE(2) adsorption onto inactivated sludge was spontaneous (Delta G=-15.18 to -16.35 kJ/mol), enthalpy-driven (Delta H=-27.2 kJ/mol), entropy-retarded (DeltaS=-39.18 J/(mol K)), and mainly physical adsorption. Effects of pH, ionic strength and coexisting organic matters (methanol and bisphenol A) on EE(2) adsorption onto inactivated sludge were also examined. The amounts of EE(2) equilibrium adsorption ability were unchanged as the pH values increasing from 2.0 to 6.0, but decreased from 2.14 to 1.43 mg/g MLSS when the initial EE(2) concentration was 5.0mg/L as pH above 6.0. The adsorption capacities were first increased from 2.19 to 2.50mg/g MLSS, then sharply decreased and stabilized at 1.12 mg/g MLSS during the ionic strength was adjusted from 0 to 1 mol/L. Methanol (0.4-5%, v/v) and bisphenol A (0-200mg/L) in the mixed liquor can decrease the adsorption capacity of EE(2) from 2.19 to 1.39 and 0.75 mg/g MLSS, respectively.

Equilibrium of Homochiral Oligomerization of a Mixture of Enantiomers. Its Relevance to Nonlinear Effects in Asymmetric Catalysis

The origin of nonlinear effects (no proportionality between enantiomeric excess (ee) of chiral auxiliary and ee of product) is first summarized in general terms, underlining the importance of the presence of molecular species bearing several moieties deriving from the chiral auxiliary. The presence of a heterochiral species, produced from enantioimpure chiral auxiliaries, usually explains well the deviation to linearity, especially asymmetric amplification. In this article it is shown that the absence of a heterochiral species is not incompatible with an asymmetric amplification. The demonstration has been done on a simple model, the equilibrium of homochiral dimerization. The monomers R and S being in equilibrium with the dimers R(2) and S(2), it was possible to calculate ee(monomer) and ee(dimer) as a function of the initial concentration and the initial ee of the monomer. The asymmetric amplification can be quite substantial for the dimer, while asymmetric depletion characterizes the residual monomers. Similar conclusions apply to homochiral tri- and tetramerizations. The extension to irreversible reactions was briefly analyzed as well as the use of these results.

Degradation of 17α-ethinylestradiol in aqueous solution by ozonation

This study investigates the ozonation of 17α-ethinylestradiol (EE 2) in aqueous solution. The affecting factors on the degradation of EE 2 were studied and described in details, such as initial EE 2 concentration, initial pH value and ozone concentration. In addition, some parameters such as pH, electrical conductivity, mineralization efficiency and degradation products were monitored during the process. The mineralization efficiency of EE 2 could reach 53.9%. During the ozonation process the rapid decrease of pH and the sharp increase of electrical conductivity indicated the formation of acidic by-products, small fragments and ions which were confirmed by high performance liquid chromatography (HPLC) and gas chromatography–mass spectrometry (GC/MS) analysis. Results showed that there were intermediate products of smaller molecule with higher polarity produced during the course of EE 2 degradation. Then a possible reaction pathway for EE 2 degradation involving all intermediates detected is proposed. During the ozonation process EE 2 was first oxidized into hydroxyl-semiquinone isomers which were subsequently degraded into low molecular weight compounds such as oxalic acid, malonate, glutarate, and so on. Furthermore, these organic acids are easily oxidized by ozone into carbon dioxide (CO 2). This work shows that ozonation process is promising for the removal of EE 2. The results can provide some useful information for the potential treatment of EE 2 by ozonation in aqueous solution.

Potential and Limitations of Palladium–Cinchona Catalyst for the Enantioselective Hydrogenation of a Hydroxymethylpyrone

The palladium-catalyzed enantioselective hydrogenation of 4-hydroxy-6-methyl-2-pyrone afforded up to 85% excess to the (S)-enantiomer of the corresponding 5,6-dihydropyrone, under very mild conditions (1 bar, room temperature). This is the highest enantioselectivity achieved so far with chirally modified Pd, demonstrating the potential of this catalyst in the enantioselective hydrogenation of unsaturated compounds. A complicating feature of the reaction is the limited stability of cinchonidine under reaction conditions, which results in a decline of the initial enantiomeric excess (ee) with reaction time. Continuous feeding of a minute amount of cinchonidine during reaction allows maintenance of the high initial ee with an overall substrate/modifier molar ratio of ca. 20.

An Efficient Asymmetric Route to 2,3-Diaminobutanoic Acids

An Efficient Asymmetric Route to 2,3-Diaminobutanoic Acids

Nature of Initial Transient Period during Enantioselective Hydrogenation on Pt and Pd

The enantioselective hydrogenation of ethyl pyruvate, trifluoroacetophenone, and tiglic acid has been studied over cinchonidine-modified Pt/alumina or Pd/alumina catalysts.In situmeasurement of the catalyst potential during reaction, cyclic voltammetric, and FTIR studies were used to elucidate the nature of the initial transient period. The studies demonstrate that the recently reported surprising change of enantiomeric excess (ee) with the conversion of ethyl pyruvate cannot be considered as an intrinsic feature of the catalyst system, because it is mainly caused by impurities in ethyl pyruvate (0.6–1.9% racemic ethyl lactate even after distillation) and irreversible (destructive) adsorption of ethanol or propanol used as solvents. The initial adsorption of ethyl pyruvate on Pt was also found to be irreversible, producing considerable contamination of the Pt surface by linearly bonded CO and CxHyOztype organic residues. Astonishingly, this side reaction suppressed the initial ee only by a few percent in the presence of hydrogen and acetic acid as solvent. These findings provide a plausible explanation for the positive influence of high surface hydrogen concentration (high pressure, efficient mixing) on the initial and final ee in ethyl pyruvate hydrogenation and for the outstanding enantioselectivity obtained in acetic acid solvent. The observed contamination renders the value of any kinetic or mechanistic analysis of enantioselective hydrogenation reactions over Pt inalcoholic solventsquestionable. The hydrogenation of the carbonyl group of trifluoroacetophenone with cinchonidine-modified Pt/alumina and that of the C=C double bond of tiglic acid with cinchonidine-modified Pd/alumina provide further examples on the increase of ee during the initial transient period and on the strong influence of impurities.

Effects of drying as a preservation technique on nutrient contents of beef

Effects of different drying methods (sun drying, oven drying & rural cooker smoking) and meat size (block, flat & mince) on the nutrient content of beef was investigated with cooked cured (CC) or non-cooked cured (NC) beef. Both physical and chemical assessment were done to assess the quality of meat. Organoleptically all the samples were in acceptable condition upto 120 days of storage time. The initial (30 days) DM, CP, EE and ash content, of the samples (g/100 g DM) were ranged from 81.32-90.00, 69.00-80.16, 2.90-5.23 and 15.00-18.01, respectively. The DM, CP and EE decreased and ash content increased with increasing storage time. At the end of 120 days of storage the DM, CP, EE and ash content of the samples (g/100 g DM) ranged from 79.00-87.36, 67.24-77.92, 1.90 - 4.00 and 19.00 - 24.70, respectively. DM and CP content in cooked meat was higher than non-cooked meat. However, cooked meat contains less EE and ash value than non-cooked meat. At the end of storing time rural smoked cooked block contain highest protein (77.92%) and oven dried non-cooked mince meat (67.24%) contain lowest protein percent. Statistical analysis revealed that there was a significant (P<0.5 to 0.01) effect of drying methods and meat size on cooked or non-cooked meat. The nutrient contents of meat sample degraded significantly (P<0.05 to 0.01) with the elapse of storage time. The quality decreasing trend was lower in smoked, cooked, flat size meat sample. From this study it was observed that rural cooker smoking method of meat drying could be a useful technique of meat preservation. Keywords: Drying methods; Meat sizes; Beef preservation; Nutrient content DOI: 10.3329/jbau.v7i1.4800 J. Bangladesh Agril. Univ. 7(1): 63-68, 2009