Novel Carboxyl Esterase Preparations for the Resolution of Linalyl Acetate

 Biocatalytic resolution of the tertiary terpene alcohol (±)-linalool was accomplished via hydrolysis of its corresponding acetate ester using two highly enantiospecific enzymes (E > 100). The latter were identified in a crude cell-free extract of Rhodococcus ruber DSM 43338 and could be separated by (partial) protein purification. Since they showed opposite enantiopreference, they were termed (R)- and (S)-linalyl acetate hydrolase (LAH). The activity and selectivity of the enzyme preparations was markedly dependent on the fermentation conditions.     

Solvothermal Syntheses,Crystal Structures,and Properties of New [Mn(<Emphasis Type="BoldItalic">dien</Emphasis>)<Subscript>2</Subscript>]<Superscript>2+</Superscript> Complexes

Summary.  The two new compounds Mn(dien)₂[MoS₄] (1) and Mn(dien)₂[Mo₂O₂S₆] (2) (dien = diethylenetriamine) were prepared under solvothermal conditions. Both compounds were obtained as phase-pure products. The structures consist of new [Mn(dien)₂]²⁺ cations and isolated tetrahedral [MoS₄]²⁻ (1) or [Mo₂O₂S₆]²⁻ (2) anions. Between the anions and the cations, hydrogen bonding is observed. Compound 1 crystallizes in the tetragonal space group I (a = 10.219(2), c = 9.259(2) ?, Z = 2), whereas 2 crystallizes in the monoclinic space group P2₁/c (a = 8.703(2), b = 18.390(4), c = 14.603(3) ?, β = 103.18(3)°, Z = 4). The thermal behaviour of the thiomolybdates was investigated using difference thermoanalysis (DTA) and thermogravimetry (TG). Both compounds decompose under argon with a single endothermic signal in the DTA curve (peak maximum: 252 (1) and 242°C (2)). Received November 5, 2001. Accepted December 27, 2001     

Structural, Spectroscopic, and Thermal Behaviour of Bis-(thiosaccharinate)-aqua-cadmium(II)

Summary.  The crystal structure of the title complex, [Cd(tsac)₂(H₂O)], has been determined by single crystal X-ray diffraction methods. It crystallizes in the monoclinic space group C2/c (a = 12.236(3), b = 8.919(3), c = 16.655(3) ?, β = 96.18(2)°, Z = 4). The molecular structure was solved from 1705 independent reflections with I > σ(I) and refined to R ₁ = 0.0489. Infrared and Raman spectra of the complex were recorded and are briefly discussed. Its thermal behaviour was investigated by thermogravimetry and differential thermal analysis. Received December 18, 2000. Accepted February 19, 2001     

Polymorphism and Pressure Driven Thermal Spin Crossover Phenomenon in [Fe( abpt )2(NC X )2] ( X =?S, and Se): Synthesis, Structure and Magnetic Properties

Summary.  The monomeric compounds [Fe(abpt)₂(NCX)₂] (X = S (1), Se (2) and abpt = 4-amino-3,5-bis(pyridin-2-yl)-1,2,4-triazole) have been synthesized and characterized. They crystallize in the monoclinic P2₁/n space group with a = 11.637(2) ?, b = 9.8021(14) ?, c = 12.9838(12) ?, β = 101.126(14)°, and Z = 2 for 1, and a = 11.601(2) ?, b = 9.6666(14) ?, c = 12.883(2) ?, β = 101.449(10)°, and Z = 2 for 2. The unit cell contains a pair mononuclear [Fe(abpt)₂(NCX)₂] units related by a center of symmetry. Each iron atom, located at a molecular inversion center, is in a distorted octahedral environment. Four of the six nitrogen atoms coordinated to the Fe(II) ion belong to the pyridine-N(1) and triazole-N(2) rings of two abpt ligands. The remaining trans positions are occupied by two nitrogen atoms, N(3), belonging to the two pseudo-halide ligands. The magnetic susceptibility measurements at ambient pressure have revealed that they are in the high-spin range in the 2 K–300 K temperature range. The pressure study has revealed that compound 1 remains in high-spin as pressure is increased up to 4.4 kbar, where an incomplete thermal spin crossover appears at around T _1/2 = 65 K. Quenching experiments at 4.4 kbar have shown that the incomplete character of the conversion is a consequence of slow kinetics. Relatively sharp spin transition takes place at T _1/2 = 106, 152 and 179 K, as pressure attains 5.6, 8.6 and 10.5 kbar, respectively. Corresponding author. E-mail: jose.a.real@uv.es Received June 12, 2002; accepted July 1, 2002     

LC–MS–MS determination of ibuprofen, 2-hydroxyibuprofen enantiomers,and carboxyibuprofen stereoisomers for application in biotransformation studies employing endophytic fungi

The purpose of this study was the development and validation of an LC–MS–MS method for simultaneous analysis of ibuprofen (IBP), 2-hydroxyibuprofen (2-OH-IBP) enantiomers, and carboxyibuprofen (COOH-IBP) stereoisomers in fungi culture medium, to investigate the ability of some endophytic fungi to biotransform the chiral drug IBP into its metabolites. Resolution of IBP and the stereoisomers of its main metabolites was achieved by use of a Chiralpak AS-H column (150 × 4.6 mm, 5 μm particle size), column temperature 8 °C, and the mobile phase hexane–isopropanol–trifluoroacetic acid (95: 5: 0.1, v/v) at a flow rate of 1.2 mL min⁻¹. Post-column infusion with 10 mmol L⁻¹ ammonium acetate in methanol at a flow rate of 0.3 mL min⁻¹ was performed to enhance MS detection (positive electrospray ionization). Liquid–liquid extraction was used for sample preparation with hexane–ethyl acetate (1:1, v/v) as extraction solvent. Linearity was obtained in the range 0.1–20 μg mL⁻¹ for IBP, 0.05–7.5 μg mL⁻¹ for each 2-OH-IBP enantiomer, and 0.025–5.0 μg mL⁻¹ for each COOH-IBP stereoisomer (r ≥ 0.99). The coefficients of variation and relative errors obtained in precision and accuracy studies (within-day and between-day) were below 15%. The stability studies showed that the samples were stable (p > 0.05) during freeze and thaw cycles, short-term exposure to room temperature, storage at −20 °C, and biotransformation conditions. Among the six fungi studied, only the strains Nigrospora sphaerica (SS67) and Chaetomium globosum (VR10) biotransformed IBP enantioselectively, with greater formation of the metabolite (+)-(S)-2-OH-IBP. Formation of the COOH-IBP stereoisomers, which involves hydroxylation at C3 and further oxidation to form the carboxyl group, was not observed.     

On the Chemistry of the Resveratrol Diastereomers

Summary.  The (E)- and (Z)-diastereomers of resveratrol were investigated with respect to their photochemical and thermal diastereomerization reactions. The free enthalpy difference between the two diastereomers was estimated to be in the order of common stilbenes, with the (E)-diastereomer more stable by about 11–14 kJ mol⁻¹. The Arrhenius activation barrier of about 280 kJ mol⁻¹ was found to be quite high and implies that thermal equilibration cannot account for the (Z)-diastereomer found in nature. A preparative access to the (Z)-diastereomer by photodiastereomerization is described. The ¹H and ¹³C NMR spectra of the two diastereomers were assigned and their absorption spectra and fluorescence quantum yields of the neutral and monodeprotonated species were determined. Corresponding author. E-mail: heinz.falk@jku.at Received October 15, 2002; accepted November 7, 2002 Published online February 20, 2003     

A Dehydrogenated Cycloadduct of N-Phenylmaleimide and the Azomethine Ylide Derived from Ninhydrine and Phenylalanine: Structure and Conformation

Summary.  The structure of the dehydrogenation product 1′,3a′-dihydro-3′-((1,3-dioxoindan-2-ylidene)-phenyl-methyl)-5′-phenyl-spiro-(indan-2,1′-pyrrolo[3,4-c]pyrrole)-1,3,4′,6′-(5′H, 6a′H)-tetrone derived from the cycloadducts (±)-(3a′S,6a′R)-1′,3a′-dihydro-3′-((R)-α-(1,3-dioxoindanyl)-benzyl)-5′-phenyl-spiro-(indan-2,1′-pyrrolo[3,4-c]pyrrole)-1,3,4′,6′(5H,6a′H)-tetrone and/or (±)-(3a′S,6a′R)-1′,3a′-dihydro-3′-((S)-α-(1,3-dioxoindanyl)-benzyl)-5′-phenyl-spiro-(indan-2,1′-pyrrolo[3,4-c]pyrrole)-1,3,4′,6′(5H,6a′H)-tetrone, which were synthesized by 1,3-dipolar cycloaddition of N-phenylmaleimide to 2-((2-(1,3-dioxoindan-2-yl)-2-phenyl-ethenyl)-imino)-indan-1,3-dione, was determined by X-ray analysis. Crystal data (CCD, 180 K): rhombohedral, R&3macr;;, a = 34.0871(7), c = 13.9358(5) ?, Z = 18; the structure was solved by direct methods and refined by full-matrix least-squares procedures to R(F, I ≥ 3σ(I)) = 0.053. The molecule contains a central folded ring system of two cis-fused 5-membered heterocyclic rings; each ring is nearly planar, and the angle between the rings amounts to 59.0°. Dynamic ¹H NMR spectroscopy of the product revealed an exchange process caused by restricted rotation of the double bonded 1,3-indandione moiety and the phenyl group about the C_sp2-C_sp2 single-bonds. Molecular modeling and complete lineshape analysis indicated a four site exchange process for which free energies of activation and free energies could be established. ΔG ^‡ values for the barriers of rotation are in the range of 57–59 kJ · mol^− 1 at 273 K, which is unusually high for an unsubstituted phenyl group. Received May 3, 2001. Accepted (revised) June 8, 2001     

Rapid and Simple Method for Simultaneous Determination of Escin and Diethylamine Salicylate in Pharmaceutical Preparations by Partial Least-Squares Multivariate Calibration

Summary. A partial least-squares calibration (PLS) method has been developed for simultaneous quantitative determination of escin (ES) and diethylamine salicylate (DAS) in pharmaceutical preparations. The resolution of these mixtures has been accomplished without prior separation or derivatisation, by using partial least-squares (PLS-2) regression analysis of electronic absorption spectral data. The experimental calibration matrix was constructed with 9 samples. The concentration ranges considered were 10, 20, 30 (ES) and 40, 50, 60 (DAS) μg cm⁻³. The absorbances were recorded between 200 and 325 nm every 5 nm. Proposed method was compared with conventional spectrophotometric method. The results show that PLS-2 is a simple, rapid, and accurate method applied to the determination of these compounds in pharmaceuticals.     

Two Novel Er-Cr Ion-Pair Complexeswith Hydrogen Bonding Network: Syntheses, Crystal Structures, and Magnetic Properties

Summary.  Two novel Er-Cr ion-pair complexes ([Er(DMA)₃(H₂O)₄][Cr(CN)₆] and [Er(MPL)₄(H₂O)₃][Cr(CN)₆]·2H₂O; DMA = dimethylacetamide, MPL = 1-methyl-2-pyrrolidinone) have been synthesized. [Er(DMA)₃(H₂O)₄][Cr(CN)₆] crystallizes in the monoclinic system (space group P _c ) with a = 9.789(2), b = 11.263(2), c = 13.997(3)?, β = 105.66(3)°, V = 1485.9(5)?³, Z = 2; [Er(MPL)₄(H₂O)₃][Cr(CN)₆]·2H₂O crystallizes in the monoclinic system (space group P2₁) with a = 9.447(2), b = 13.881(3), c = 14.673(3)?, β = 101.85(3), V = 1883.1(7)?³, Z = 2. X-Ray crystal diffraction analyses reveal that the two complexes form a hydrogen bonding network structure through the CN group and H₂O molecules. Variable temperature susceptibilities for the two complexes indicate that weak antiferromagnetic interactions exist between cation and anion pairs through this hydrogen bonding network.     

Amino Acid Mediated Borane Reduction of Ketones IIa

Summary.  Acetophenone, 2,2-dimethylcyclopentanone, 3,3-dimethyl-2-butanone, 3-methyl-2-butanone, and 2-pentanone were reduced with borane mediated by (S)-alanine, (S)-methionine, (S)-leucine, (S)-valine, and (S)-isoleucine in very good yields giving predominantly alcohols of (R)-configuration (ee = 23–89%). A molecular topology based model was developed for describing the influence of the substituents, both in the oxazaborolidine type reagent and in the ketone, on the observed chiral induction. Received May 31, 2001. Accepted June 25, 2001     

tris-(Benzimidazol-2-yl-methyl)-amine as a Versatile Building Block in Ru(II) Polypyridyl Chemistry

Summary.  tris-(Benzimidazol-2-yl-methyl)-amine, H₃ ntb, was prepared and used in the synthesis of dinuclear Ru(II) polypyridyl and polynuclear Ru(II)–Co(III) complexes of the type [Ru₂(H₂ ntb) (bpy)₄]³⁺, [Ru₂(Hntb)(phen)₄]²⁺, [(Ru₂(H₂ ntb)(bpy)₄)₂Co(en)₂]⁹⁺, and [(Ru₂(Hntb)(phen)₄)₂ Co(en)₂]⁷⁺ (bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, en = 1,2-diaminoethane). The complexes were characterized by elemental analysis as well as spectroscopic and redox data. The luminescent properties of the complexes were also studied. The complexes showed significant antitumour and anti-HIV activities. Received May 9, 2001. Accepted (revised) June 7, 2001     

X-Ray Diffraction and Raman Spectroscopic Study of Bis-(Pyridine Base) Complexes of Cadmium(II) Halogenides

Summary.  The molecular structures of bis-(pyridine base) complexes of cadmium(II) chloride and bromide, where the pyridine base is pyridine ( py), 3-methylpyridine (3-Me-py), 4-methylpyridine (4-Me-py), and 4-ethylpyridine (4-Et-py), were investigated by means of single-crystal X-ray diffraction and Raman spectroscopy. The crystal structures of CdCl₂ py ₂ (1), CdCl₂(3-Me-py)₂ (2), and CdCl₂(4-Me-py)₂ (3) were determined. All crystals are monoclinic; 1: a = 17.784(2), b = 8.666(1), c = 3.8252(7) ?, β = 91.54(1)°, space group: P2₁/n; 2: a = 11.89(1), b = 14.41(1), c = 3.874(6) ?, β = 92.3(1)°, space group: P2₁/a; 3: a = 21.091(2), b = 3.8884(5), c = 18.2317(3) ?, β = 113.64(1)°, space group: C2/c. The structures were refined to R/R _w values (%) of 3.2/5.5, 3.0/5.0, and 3.4/5.1 for 1–3. All cadmium atoms are octahedrally coordinated with the chloride ions forming infinite di-μ-chloro polymeric linear chains and the nitrogen atoms of the pyridine base in trans configuration. The Cd chains are oriented along the c-axis in 1 and 2 and along the b-axis in 3. The crystal structures indicate the absence of a peculiar interaction between the polymeric chains. The Raman spectra of eight complexes were measured in the range of 550–50 cm⁻¹, and the Raman peaks originating from cadmium-halogen vibrations were assigned. The Raman spectra of 1 and 2 are quite alike in the lattice mode vibration region. The resemblance of the cadmium-halogen vibration peaks indicates the same halogenide ion bridged octahedral structure for all complexes. Received March 27, 2001. Accepted (revised) June 19, 2001     

Theoretical Study of the Interactions between Isolated <Emphasis Type="Italic">DNA</Emphasis> Bases and Various Groups IA and IIA Metal Ions by <Emphasis Type="Italic">Ab Initio</Emphasis> Calculations

Summary. Interactions of the DNA bases adenine (A), guanine (G), cytosine (C), and thymine (T) with various metal ions (M) of groups IA and IIA of the periodic table of the elements were studied at the HF, MP2, and DFT levels of theory. The structures and thermodynamic stabilities of these species were studied at the gas phase. The calculations uphold that there exist two active sites in G and one in A, C, and T. The calculations also show that the O² atom in T is a more active site for metal ion bindings than that in C. The stability energies for G … M complexes are larger than those for A … M complexes and the stability energies for T … M complexes are larger than those for C … M complexes. As z/r ratio for the metal ion increases, the interaction energy for the complex increases systematically. Thermodynamic quantities such as ΔH, ΔG, ΔS, and ln K were determined for each complexation reaction, [Base+M ⁿ⁺ →(Base … M) ⁿ⁺]. A, G, and C complexation reactions except for C … Rb⁺ are exothermic. The situation is quite different for T complexation reactions and all except for T … Be²⁺ and T … Mg²⁺ are endothermic.     

Polygermanosilyne Calcium Hydroxide Intercalation Compounds Formed by Topotactic Transformation of Ca(Si 1 − x Ge x )2 Alloy Zintl Phases in Ambient Atmosphere

Summary.   Epitaxial thin films of Ca(Si _1 − x Ge _x )₂ with 0 < x ≤ 1 are found to react with the moisture of ambient atmosphere to form new Ca-Si-Ge-O-H compounds which were studied by X-ray diffraction, energy dispersive X-ray analysis, infrared absorption, and thermally induced hydrogen desorption measurements. Pure CaGe₂ forms the polygermyne calcium hydroxide intercalation compound Ca(OH)₂(GeH)₂ upon exposure to humidity, with a trigonal tr6 crystal lattice with a = 4.00(1) and c = 65.3(1)?. In mixed Ca(Si _1 − x Ge _x )₂ with smaller Ge content, the group-14 layers are subject to intense oxidation leading to decreased crystallinity. The products exhibit characteristic colours and intense photoluminescence, the peak luminescence varying from 1.35 eV for the reaction product of Ca(Si_0.3Ge_0.7)₂ to 2.6 eV for that of Ca(Si_0.5Ge_0.5)₂. Received March 12, 2001. Accepted (revised) May 2, 2001     

The Thermal Diastereomerization of the Tryptophane-Derived Green Fluorescent Protein Chromophore

Summary. Two model compounds for the tryptophane variant of the green fluorescent protein chromophore containing a 3-indolyl and 2-pyrrolyl moiety were prepared. For the first one the (Z)-diastereomer was found to be more stable than the (E)-diastereomer by 5.7 kJ mol⁻¹. It could be photo-diastereomerized and its thermal equilibration was studied, whereas the second one underwent photo-destruction. From an Arrhenius plot an activation barrier for the (E) to (Z) diastereomerization of 85.6 kJ mol⁻¹ could be determined. Thus, it could be demonstrated that in contrast to the corresponding phenyl derivative studied recently the tyrosine- and tryptophane-derived chromophores of the green fluorescent protein are amenable to fast thermal diastereomerization, which is of fundamental importance for the fluorescence and photoswitching processes in the corresponding proteins.     

An ab initio Molecular Orbital Study of the Conformational Properties of all-(Z)-Cyclododeca-1,4,7,10-tetraene

Summary.  Ab initio HF/6-31G^* and MP2/6-31G^*//HF/6-31G^* methods were used to calculate the structure optimization and conformational interconversion pathways for all-(Z )-cyclododeca-1,4,7,10-tetraene. This compound adopts the symmetrical crown (C _4v) conformation. Ring inversion takes place via symmetrical intermediates, such as boat-chair (BC, C _s) and twist (C _2h) conformers and requires about 22.3 kJ · mol⁻¹. The calculated strain energies for BC and twist conformers are 5.9 and 13.5 kJ · mol⁻¹. The results of semiempirical AM1 calculations for structural parameters and relative energies of the important geometries of the title compound are in good agreement with the results of ab initio methods. Received July 9, 2001. Accepted September 26, 2001     

Phase Gratings in Photoreactive Polymers:A Way to Optically Pumped Organic Lasers

Summary.  Poly-(4-vinylbenzyl-thiocyanate) (PVBT) was investigated as a photoreactive polymer which changes its refractive index upon UV irradiation as is required for the production of phase gratings. After UV irradiation, the refractive index of PVBT films increased from n_D ²⁰ = 1.629 to n_D ²⁰ = 1.660 (Δn = +0.031). The change in the refractive index resulted mainly from the photoinduced isomerization of thiocyanate (SCN) to isothiocyanate (NCS) groups. It was possible to modify irradiated PVBT with 1-naphthylmethyl amine which lead to a further increase of the refractive index. Both the isomerization and the modification were followed with FTIR spectroscopy. This modification of the irradiated zones also yields an advantageous stabilization of phase gratings enscribed in PVBT. The investigations were carried out in the realm of novel organic distributed feedback (DFB) lasers. Received August 22, 2000. Accepted September 22, 2000     

Solvothermal Syntheses, Crystal Structures, and Properties of New [Mn( dien )2]2+ Complexes

 The two new compounds Mn(dien)₂[MoS₄] (1) and Mn(dien)₂[Mo₂O₂S₆] (2) (dien = diethylenetriamine) were prepared under solvothermal conditions. Both compounds were obtained as phase-pure products. The structures consist of new [Mn(dien)₂]²⁺ cations and isolated tetrahedral [MoS₄]²⁻ (1) or [Mo₂O₂S₆]²⁻ (2) anions. Between the anions and the cations, hydrogen bonding is observed. Compound 1 crystallizes in the tetragonal space group I (a = 10.219(2), c = 9.259(2) ?, Z = 2), whereas 2 crystallizes in the monoclinic space group P2₁/c (a = 8.703(2), b = 18.390(4), c = 14.603(3) ?, β = 103.18(3)°, Z = 4). The thermal behaviour of the thiomolybdates was investigated using difference thermoanalysis (DTA) and thermogravimetry (TG). Both compounds decompose under argon with a single endothermic signal in the DTA curve (peak maximum: 252 (1) and 242°C (2)).     

Two-Phase Aqueous Extraction of Chromium and its Application to Speciation Analysis of Chromium in Plasma

 This work proposes a new extraction method for chromium based on the two-phase aqueous system isopropyl alcohol-ammonium sulfate-ammonium thiocyanate (i-PrOH-(NH₄)₂SO₄-NH₄SCN), and the related experimental conditions are optimized. The results show that chromium (III) can be quantitatively extracted under the selected conditions: 4 mL of i-PrOH, 200 μL of 2 mol/L sulfuric acid, 1 mL of 4 mol/L NH₄SCN and 3 mL of saturated (NH₄)₂SO₄ solution (V_total=10 mL). Application of the proposed method to speciation analysis of plasma chromium was also investigated and satisfactory results were obtained. Received May 22, 1999. Revision November 8, 1999.     

Development of a liquid chromatography-mass spectrometry method for the determination of ursolic acid in rat plasma and tissue: application to the pharmacokinetic and tissue distribution study

A fast and sensitive liquid chromatography–mass spectrometry method was developed for the determination of ursolic acid (UA) in rat plasma and tissues. Glycyrrhetinic acid was used as the internal standard (IS). Chromatographic separation was performed on a 3.5 μm Zorbax SB-C18 column (30 mm × 2.1 mm) with a mobile phase consisting of methanol and aqueous 10 mM ammonium acetate using gradient elution. Quantification was performed by selected ion monitoring with (m/z)⁻ 455 for UA and (m/z)⁻ 469 for the IS. The method was validated in the concentration range of 2.5 − 1470 ng mL⁻¹ for plasma samples and 20 − 11760 ng g⁻¹ for tissue homogenates. The intra- and inter-day assay of precision in plasma and tissues ranged from 1.6% to 7.1% and 3.7% to 9.0%, respectively, and the intra- and inter-day assay accuracy was 84.2 − 106.9% and 82.1 − 108.1%, respectively. Recoveries in plasma and tissues ranged from 83.2% to 106.2%. The limits of detections were 0.5 ng mL⁻¹ or 4.0 ng g⁻¹. The recoveries for all samples were >90%, except for liver, which indicated that ursolic acid may metabolize in liver. The main pharmacokinetic parameters obtained were T _max = 0.42 ± 0.11 h, C _max = 1.10 ± 0.31 μg mL⁻¹, AUC = 1.45 ± 0.21 μg h mL⁻¹ and K _a = 5.64 ± 1.89 h⁻¹. The concentrations of UA in rat lung, spleen, liver, heart, and cerebellum were studied for the first time. This method is validated and could be applicable to the investigation of the pharmacokinetics and tissue distribution of UA in rats.