Search

Lipases and subtilisins are versatile enzymes capable of showing high enantioselectivity and broad substrate specificity simultaneously. The transition-state models previously proposed to rationalize this important feature were intensively examined from kinetic and thermodynamic viewpoints. Kinetic measurements reaffirmed that chiral discrimination originates from the transition state and that the enantioselectivity results from the reduced activity of the enzymes for the slower-reacting enantiomer, but not from the enhanced activity for the faster-reacting enantiomer relative to a reference alcohol, cyclopentanol. The larger substituent of the slower-reacting enantiomers interacts repulsively with the protein in the transition state, and even the larger substituent of the faster-reacting enantiomers interacts unfavorably to some degree with the protein. A number of thermodynamic parameters, ΔΔH‡ and ΔΔS‡, for the subtilisin-catalyzed acylations of secondary alcohols were determined. A linear compensation effect was found between the ΔΔH‡ and ΔΔS‡ values. As the ΔΔH‡ value becomes negatively large, the ΔΔS‡ value also becomes negatively large. This observation is explained in terms of the transition-state model. Because the widely accepted concepts such as the lock-and-key mechanism and the induced-fit mechanism cannot account for the peculiar behavior of these enzymes toward unnatural substrates, a new category, the non-lock-and-key mechanism, has been proposed. [Copyright &y& Elsevier]

It has been demonstrated that lipase is useful not only for kinetic resolution but also for the rapid determination of absolute configurations. We have previously proposed a mechanism represented by transition-state models to rationalize the enantioselectivity in the lipase- and subtilisin-catalyzed kinetic resolutions of secondary alcohols. The mechanism indicates that the enzyme-catalyzed reactions can be used as a tool for determining the absolute stereochemistry of secondary alcohols. In order to increase reliability, the enzymatic method was combined with Mosher''s method using MTPA, to give a protocol which is named the double-confirmation method. The absolute configurations of six 1-substituted ethanols were determined consistently by this new procedure. The enzymatic method is quick, easy, economical, and reliable. An interesting similarity in conformation between the transition-state models and MTPA esters is also described. [Copyright &y& Elsevier]

Examines the transition state conformation in hydrolase-catalyzed enantioselective transesterifications. Synthesis of porphyrin; Derivation of the lipase-catalyzed kinetic resolution of secondary alcohols; Use of transition-state models for chemoenzymatic synthesis.

Size and location of a necrotic lesion are considered important factors predicting collapse of the femoral head in the early stages of osteonecrosis. However, few analytical studies have performed a three-dimensional quantification of lesions to clarify how these two morphological factors are related to the occurrence of collapse. We evaluated the relevance of lesion size and location for prediction of collapse quantitatively using new three-dimensional indexes. Magnetic resonance (MR) imaging was performed in 65 hips in a consecutive series of 47 patients with osteonecrosis without radiological evidence of collapse. Lesion volume as well as latitude and longitude of the center of gravity of the lesion within the femoral head were calculated. Thirty-three hips developed radiological collapse, while in the remaining 32 hips collapse did not occur over 2 years. Multiple logistic regression analysis showed a significant relationship between lesion volume and radiological collapse. In 35 hips in which the lesion volume was less than 30% of the femoral head, only 9 collapsed. In comparison with non-collapsed hips, collapsed hips had a significantly higher combined value for latitude and longitude of the lesion, corresponding to the anterosuperior portion of the femoral head. Quantitative analysis of lesion morphology demonstrated that lesion volume is strongly correlated with risk of collapse, and that lesion location is an important prognostic indicator of collapse in small necrotic lesions. [Copyright &y& Elsevier]

Focuses on the purification of an dihydromicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase, which shows reducing activity for 1-chloro-2-hexanone from bakers' yeast. Procedure of the asymmetric reduction of several cabonyl compounds using purified reductase; What the reductase showed; Determination of the kinetic parameters of the reductase.

Presents information pertaining to the chemical properties of the enantioselective synthesis. Importance of the optically active butenolide; Description of the total syntheses of the ethisolide, whisky lactone, and (-)-avenaciolide from the butenolides; How the enantiomeric excess was determined.

Twenty-eight depressed patients receiving amoxapine with ages ranging from 21 to 68 years (male 12, female 16) were studied in order to clarify the age effect on plasma levels of amoxapine and its major active metabolite, 8-OH amoxapine. Plasma amoxapine levels were determined by both radioreceptor assay (RRA) and gas liquid chromatography (GLC). Plasma levels of 8-OH amoxapine were also determined by GLC. A highly significant correlation was found for plasma levels of amoxapine determined by RRA and GLC (r = 0.88, p < 0.001). There was no significant correlation between the amoxapine daily dose (mg/kg) and its plasma levels determined either by RRA or GLC. The ratios of plasma amoxapine level by RRA and GLC to daily dose significantly increased with advancing and (p < 0.05) and a significant positive correlation was also found between the ratio of plasma of 8-OH amoxapine to daily dose and the age of the patients (p < 0.01) suggesting that the plasma 8-OH amoxapine levels were more strongly affected by age than the parent drug. These results indicate that the metabolism of amoxapine in the liver decreases with age as well as that of other tricyclic antidepressants reported previously. The higher correlation of 8-OH amoxapine with patient's age may be mainly due to its renal excretion which may also decrease with age. [ABSTRACT FROM AUTHOR]

Background: Pulmonary NUT carcinoma is rare, but lethal, thus, must not be overlooked. The definitive diagnosis is made by a NUT monoclonal antibody or gene analysis, but these are not always routinely available. Therefore, the diagnosis depends on this rare disease being suspected from the clinical and pathological findings. Generally, NUT carcinoma of the lung occurs near the hilum in younger adults with severe subjective symptoms. Histologically, it is characterized by the monomorphic growth of small cells which showed positivity of p63 immunohistochemistry. Case presentation: An 82-year-old man was referred for an incidental finding of an abnormal shadow at the peripheral apex of the right lung on computed tomography for a regular follow-up examination of renal cancer. Microscopically, small cell carcinoma was initially suspected; however, immunohistochemistry was not typical. NUT carcinoma with BRD4-NUT fusion was ultimately diagnosed using a NUT monoclonal antibody, fluorescence in situ hybridization, and RNA-seq. p63 and p40 protein expression was not detected. Conclusions: This is the first case of pulmonary NUT carcinoma to show negativity for p63 and is the oldest among previously reported cases. The present case suggests that NUT carcinoma should be suspected when the morphology of monomorphic growth of small cells without lineage-specific differentiation, regardless of age, clinical symptoms, the tumor location, or p63 expression. [ABSTRACT FROM AUTHOR]

Chiral diporphyrin receptor 1, which has a macrocyclic cavity to sandwich aromatic guest molecules viadouble π–π stacking interactions, enabled the naked-eye detection of an aromatic explosive as well as chiral discrimination in NMR. [ABSTRACT FROM AUTHOR]

α,α,α-Trifluoroacetophenone (2), which is susceptible to noncatalytic reduction by BH3, could be reduced to chiral alcohol up to 90% ee by using electronically tuned-CBS catalyst (1) with BH3. The enantioselectivities highly correlated with the differential orbital energies between 1-BH3 adduct and 2, which were calculated by DFT method. [ABSTRACT FROM AUTHOR]

Catalytic activity and enantioselectivity of lipase toward poor substrates bearing bulky substituents on both sides have been dramatically improved by rational design; the Evalue for a poor substrate was increased from 5 (wild-type enzyme) to >200 (I287F/I290A double mutant) with an acceleration of the reaction rate. [ABSTRACT FROM AUTHOR]

The existence of the intermolecular interaction in CDCl3between oxygen of MeOH and the C6F5group is demonstrated. [ABSTRACT FROM AUTHOR]

Reports on the high enantioselectivity and broad substrate specificity of a carbonyl reductase. Overview on the procedure for the purification of the enzyme and asymmetric reductions; Obtaining optically active alcohols useful for organic synthesis by the enzymatic reductions; Transformation of aliphatic and aromatic ketones; Stereochemical trend in the enzymatic reductions.

The original publication of this paper contain an error for the first name and last name of the second author have been mixed up as "Wenliang, Z.". [ABSTRACT FROM AUTHOR]

This article discusses various issues related to simple and efficient fabrication of room temperature stable electride in relation to melt-solidification and glass ceramics. Electrides are ionic compounds in which electrons act as anions. These compounds are promising for practical applications such as reducing agents, cold-cathode electron-field emissions, thermionic power generation, and refrigeration devices. However, fatal drawbacks such as the thermal and chemical instability of organic electrides at room temperature (RT) have impeded their applications. Here, the article authors show that RT stable C 1 2A7 electrides can be simply synthesized via a strongly reducing Cl 2A7 "melt", i.e., a direct solidification of the melt- solidification or a crystallization of the glass ceramics.

A highly active Mg-porphyrin catalyst for the synthesis of cyclic carbonates from epoxides and CO2 under solvent-free conditions showing a TON of up to 103000 is presented. [ABSTRACT FROM AUTHOR]