QSAR study of the enantiomeric excess in asymmetric catalytic reactions with topological indices and an artificial neural network

The relationships between the enantiomer excess of product in catalytic asymmetric reactions and the structures of the catalysts or reagents in several asymmetric reactions were studied using a backpropagation (BP) neural network with topological indices and their chiral expansions. The trained network can be used to screen new asymmetric catalysts, estimate catalytic effects, design reaction environments, and prove or improve the proposed reaction mechanism.     

Pinus halepensis,Pinus pinaster,Pinus pinea and Pinus sylvestris Essential Oils Chemotypes and Monoterpene Hydrocarbon Enantiomers,before and after Inoculation with the Pinewood Nematode Bursaphelenchus xylophilus

Pinewood nematode (PWN), Bursaphelenchus xylophilus, is the causal agent of pine wilt disease, a serious threat to global forest populations of conifers, especially Pinus spp. A time‐course study of the essential oils (EOs) of 2‐year‐old Pinus halepensis, Pinus pinaster, Pinus pinea and Pinus sylvestris following inoculation with the PWN was performed. The constitutive and nematode inoculation induced EOs components were analyzed at both the wounding or inoculation areas and at the whole plant level. The enantiomeric ratio of optically active main EOs components was also evaluated. External symptoms of infection were observed only in P. pinaster and P. sylvestris 21 and 15 days after inoculation, respectively. The EO composition analysis of uninoculated and unwounded plants revealed the occurrence of chemotypes for P. pinaster, P. halepensis and P. sylvestris, whereas P. pinea showed a homogenous EO composition. When whole plants were evaluated for EO and monoterpene hydrocarbon enantiomeric chemical composition, no relevant qualitative and quantitative differences were found. Instead, EO analysis of inoculated and uninoculated wounded areas revealed an increase of sesquiterpenes and diterpenic compounds, especially in P. pinea and P. halepensis, comparatively to healthy whole plants EOs.     

Biochemical properties and potential applications of an organic solvent-tolerant lipase isolated from Serratia marcescens ECU1010

An extracellular lipase was purified to homogeneity with a purification factor of 5.5-fold from a bacterial strain Serratia marcescens ECU1010. The purified lipase is a dimer with two homologous subunits, of which the molecular mass is 65 kDa, and the pI is 4.2. The pH and temperature optima were shown to be pH 8.0 and 45 °C, respectively. Among p-nitrophenyl esters of fatty acids with varied chain length, the lipase showed the maximum activity on p-nitrophenyl myristate (C₁₄). The lipase was activated by some surfactants such as Gum Arabic, polyvinyl alcohol (PVA) and Pg350me, but not by Ca²⁺. The enzyme displayed pretty high stability in many water miscible and immiscible solvents. This is a unique property of the enzyme which makes it extremely suitable for chemo-enzymatic applications in non-aqueous phase organic synthesis including enantiomeric resolution. Several typical chiral compounds were tested for kinetic resolution with this lipase, consequently giving excellent enantioselectivities (E = 83 >100) for glycidyl butyrate (GB), 4-hydroxy-3-methyl-2-(2-propenyl)-2-cyclopenten-1-one acetate (HMPCA), naproxen methyl ester (NME) and trans-3-(4′-methoxyphenyl) glycidic acid methyl ester (MPGM).     

Enzymatic Resolution of Racemates Contaminated by Racemic Product

Enzyme-catalyzed kinetic resolution is sometimes performed starting with substrate already containing small amounts of the racemic product. Then the determination of the enantiomeric ratio may be seriously disturbed when this parameter is calculated from the degree of conversion and the enantiomeric excess of either the substrate or the product (Chen et al., 1982, 1987) or when it is calculated directly from the enantiomeric excess of substrate and product (Rakels et al., 1993).

This paper presents modifications of these methods in order to correctly determine the enantiomeric ratio as well as the amount of racemic product in the substrate. The theoretical predictions were verified for the hydrolysis of racemic ethyl 2-chloropropionate, catalyzed by carboxylesterase NP. Despite the presence of racemic product in the substrate, accurate and reliable values for the enantiomeric ratio were obtained by using the modified methods.     

Electrochromatographic separation of hydrophobic amino acid enantiomers by molecularly imprinted capillary columns

In the present study, the enantiomeric forms of hydrophobic amino acids (l-tryptophan, l-tyrosine, and l-phenylalanine) were separated by molecularly imprinted capillary columns (MICC) via Capillary Electrochromatography (CEC) for the first time. The monomer ratio, crosslinker ratio, template molecule ratio, the porogen ratio and type, polymerization time, and also the effect of temperature were examined to increase the permeability properties of MICC. FTIR, SEM and BET analyses were realized for the characterization of MICC. The effect of the electric field, organic solvent ratio, and pressure were carried out experimentally to determine the optimum conditions. The separation performances of MICC and the non-imprinted capillary columns (NICC) were compared electrochromatographically.     

Fluorescence determination of enantiomeric composition of pharmaceuticals via use of ionic liquid that serves as both solvent and chiral selector

A new method has been developed for the sensitive and accurate determination of enantiomeric compositions of a variety of drugs, including propranolol, naproxen, and warfarin. The method is based on the use of the fluorescence technique to measure diastereomeric interactions between both enantiomeric forms of a drug with an optically active room temperature ionic liquid (RTIL) followed by partial least squares analysis of the data. The chiral RTIL used in this study, S-[(3-chloro-2-hydroxypropyl) trimethylammonium] [bis((trifluoromethyl)sulfonyl)amide] (S-[CHTA](+) [Tf(2)N](-)), is a novel chiral RTIL that has been synthesized successfully recently in our laboratory in optically pure form using a simple one-step reaction with commercially available reagents. The high solubility power and strong enantiomeric recognition ability make it possible to use this chiral RTIL to solubilize a drug and to induce diastereomeric interactions for the determination of enantiomeric purity, that is, to use it as both solvent and chiral selector. Enantiomeric compositions of a variety of pharmaceutical products with different shapes, sizes, and functional groups can be determined sensitively (microgram concentration) and accurately (enantiomeric excess as low as 0.30% and enantiomeric impurity as low as 0.08%) by use of this method.     

Identification of L-3-hydroxybutyrate as an original ketone body in rat serum by column-switching high-performance liquid chromatography and fluorescence derivatization

L-3-Hydroxybutyrate (L-3HB), the enantiomer of D-3-hydroxybutyrate (D-3HB), has traditionally been regarded the "unnatural" ketone body in mammals, although there is suspicion that it is a more-favorable energy fuel for mammalian tissues than D-3HB. In this study, we demonstrated that L-3HB is an original substance in rat serum by applying fluorescence derivatization and a column-switching high-performance liquid chromatography system as the analysis technique. Racemic 3HB in rat serum derivatized using 4-nitro-7-piperazino-2,1,3-benzoxadiazole was first separated by an ODS column and was further confirmed by verifying the disappearance of the racemic 3HB peak after pretreating rat serum with D-3-hydroxybutyryl dehydrogenase. A switching valve was used to simultaneously introduce isolated racemic 3HB to the enantiomeric separation by two CHIRALCEL OD-RH columns connected in tandem. An L isomer was found to accompany the D isomer, which were quantified to be 3.98 microM (3.61%) and 106.20 microM (96.39%), respectively. Using the present analytical method, the dubious interpretation of the existence of L-3HB was clarified.     

Enantioseparation using cyclosophoraoses as a novel chiral additive in capillary electrophoresis

Cyclosophoraoses, cyclic beta-(1-->2)-D-glucans produced by Rhizobium meliloti 2011, were used as a novel chiral additive for the separation of terbutaline, amethopterin, thyroxine and N-acetylphenylalanine enantiomers in aqueous capillary electrophoresis (CE). Enantioseparation took place in the normal- or reversed-polarity mode when a high concentration of neutral (60 mM) or anionic (40 mM) cyclosophoraoses was added to the background electrolyte (BGE).     

Cyclomaltooligosaccharide (cyclodextrin)-assisted enantiomeric recognition of benzo[lmn][3,8]phenanthroline-derived amino acids

Formation of self-assembly molecular aggregates and cyclomaltooligosaccharide (cyclodextrin) molecular aggregates with benzo[lmn][3,8]phenanthroline-derived amino acids is presented. The nature of the molecular aggregates was studied by negative-ion electrospray-ionization mass spectrometry (ESIMS). The enantiomeric recognition was demonstrated by NMR enantiomeric discrimination of the amino acid derivatives in aqueous solutions of cyclodextrins.     

Enzymatic kinetic resolution of racemic ibuprofen: past,present and future

This review is a journey concerning the investigations of the kinetic resolution of racemic ibuprofen for the last 20 years. The relevancy of the pharmacological uses of the S(?+?) enantiomer along with its higher cost compared with racemic profen are the driving forces of a variety of scientific research studies addressing the enzymatic resolution of ibuprofen through enantiomeric esterification using lipases as biocatalysts. Lipases of fungal sources such as Candida rugosa, Rhizomucor miehei and the lipase B of Candida antarctica have been extensively studied both in homogeneous and heterogeneous (immobilized on solid supports) processes. In this context, the various alcohols and organic co-solvents frequently used in the esterification of racemic ibuprofen are summarized and discussed in this review. Moreover, recent investigations using membranes as reactors coupled with the separation of the desired product and microfluidic devices are presented. Finally, some guidelines about future perspectives regarding the technology of the kinetic resolution of profens and research niches are given.