Template synthesis and structures of bis-ferrocenylboronate macrobicyclic iron(ii) tris-dioximates

A series of ferrocenylboron-capped tris-dioximate iron(ii) clathrochelates was synthesized by the template condensation of three molecules of dimethylglyoxime (H₂Dm), cyclohexanedione 1,2-dioxime (H₂Nx), or cyclooctanedione 1,2-dioxime (H₂Ox) and two molecules of ferrocenylboronic acid (FcB(OH)₂) on the Fe²⁺ ion matrix. The yields of the clathrochelate derivatives of alicyclic dioximes were substantially higher than that of their acyclic analog, because the molecules of alicyclic H₂Nx and H₂Ox α-dioximes have the s-cis-configuration suitable for complex formation, whereas the H₂Dm molecules in solution have the s-trans-configuration. The synthesized compounds were characterized using elemental analysis, IR and UV-Vis spectroscopies, MALDI-TOF mass spectrometry, ¹H and ¹³C{¹H} NMR and ⁵⁷Fe Mössbauer spectroscopies, and X-ray diffraction analysis. The crystal of FeDm₃(BFc)₂·CHCl₃ contains two types of crystallographically nonequivalent clathrochelate molecules. The intermolecular contacts C-H?Cp formed by the ferrocenyl fragments and cyclooctane carbocycles and the interactions Cp-H?O were observed in the crystal of FeOx₃(BFc)₂. The structural lability of the cyclooctane substituents allows the FeOx₃(BFc)₂ molecules to arrange by the “bump-into-hollow” mode because of attractive H?H interactions between the ribbed substituents of the neighboring molecules. The geometry of the ferrocenylborate iron(ii) clathrochelates is intermediate between a trigonal prism and a trigonal antiprism.     

Reactions of acyl azides with secondary amines in the presence of copper(ii) acetate

The nucleophilic substitution of the azide group in acyl azides for secondary amines in the presence of copper(ii) acetate was studied. The formation of the corresponding amides and copper(ii) azide in the course of the reaction was observed. The shift of the absorption band of stretching vibrations of the azide group was observed in the IR spectra of the reaction products, which could be explained by the intermediate formation of a complex of acyl azide with the amine complex of copper(ii) acetate and by its decomposition to form copper(ii) azide and the corresponding amide. A blue-green color of the solution characteristic of copper(ii) acetate changed in the course of the reaction to the brown color of a solution of copper(ii) azide.     

Cis-Cycloprolylprolin-Anion-ein konfigurationsstabiles Carbanion

The racemisation ofcyclo-(l-Pro?l-Pro) (2) with metal amides in liq. ammonia was examined. The K-kation causes more extensive racemisation than Na-kation, which in turn is more effective than Li⁺. This, the racemisation of2 int-butyl alcohol with K⁺C₆H₅O^? and the data gained from corresponding deuterated medium show that the racemisation of2 proceeds in two steps: in the first, the less stabletrans-cyclo-(l-Pro?d-Pro) (3) is formed, followed by the rapid conversion of3 to a mixture ofcyclo-(l-Pro?l-Pro) andcyclo-(d-Pro?d-Pro) in the second step.     

Enzymatic synthesis of tryptamine and its halogen derivatives selectively labeled with hydrogen isotopes

Nine isotopomers of tryptamine and its halogen derivatives, labeled with deuterium, tritium in side chain, i.e., [(1R)-²H]-, [(1R)-³H]-, 5-F-[(1R)-²H]-, 5-F-[(1R)-³H]-, 5-Br-[(1R)-²H]-, double labeled [(1R)-²H/³H]-, 5-F-[(1R)-²H/³H]-, and ring labeled [4-²H]-, and [5-²H]-tryptamine, were obtained by enzymatic decarboxylation of l-Trp and its appropriate derivatives in deuteriated or tritiated media, respectively. Intermediates: [5′-²H]-l-Trp used for further decarboxylation was synthesized by enzymatic coupling of [5-²H]-indole with S-methyl-l-cysteine, and [4′-²H]-l-Trp was obtained by isotope exchange ¹H/²H of the authentic l-Trp dissolved in heavy water induced by UV-irradiation. Doubly labeled [(1R)-²H/³H]- and 5-F-[(1R)-²H/³H]-tryptamine were obtain by decarboxylation of l-Trp or [5′-F]-l-Trp carried out in ²H³HO incubation medium.     

Exploiting thermodynamic data to optimize the enantioseparation of underivatized amino acids in ligand exchange capillary electrophoresis

Stereoselective amino acid analysis has increasingly moved into the scope of interest of the scientific community. In this work, we report a study on the chiral separation of underivatized d,l-His by ligand exchange capillary electrophoresis (LECE), utilizing accurate ex ante calculations. This has been obtained by the addition to the background electrolytes (BGE) of NaClO₄ which renders the separations “all in solution processes”, allowing to accurately calculate in advance the concentrations of the species present in solution and to optimize the system performances. To this aim, the formation of ternary complexes of Cu²⁺ ion and l-lysine (l-Lys) or l-ornithine (l-Orn) with l- and d-histidine (His), and histamine (Hm) have been studied by potentiometry and calorimetry at 25 °C and with 0.1 mol dm^?3 (KNO₃) in aqueous solution. The ternary species [Cu(L)(l-His)H]⁺ and [Cu(L)(d-His)H]⁺ (where L?=?l-Lys or l-Orn) show a slight but still detectable stereoselectivity, and the determination of ΔH° and ΔS° values allowed the understanding of the factors which determine this phenomenon. The stereoselectivity showed by the protonated ternary species has been exploited to chirally separate d,l-His in LECE, by using the binary complexes of copper(II) with l-Lys or l-Orn as background electrolytes added with the appropriate amounts of NaClO₄.

Coupling of C-amino aza-substituted heterocycles with an isocyanide ligand in palladium(ii) complex

The reaction of cis-dichlorobis(2,6-xylylisocyanide)palladium(ii) with 2-aminopyrazine affords a binuclear palladium complex, in which one of the metal atoms is involved in the palladacyclic ligand. In the contrast, the coupling of isocyanide ligands in cis-dichlorobis-(2,6-xylylisocyanide)palladium(ii) with another C-amino aza-substituted heterocycle, viz.,4-acetyl-3-amino-5-methylpyrazole, gives a mononuclear cationic palladium diaminocarbene complex. Both compounds were characterized by elemental analysis, IR spectroscopy, ¹H, ¹³C{₁H}, DEPT90/DEPT135, and ¹H,¹³C-HSQC/¹H,¹³C-HMBC NMR spectroscopy, high-resolution electrospray ionization mass spectrometry, and X-ray diffraction.     

Synthesis of ruthenium(iii) and rhodium(iii) tris-acetylacetonates and palladium(ii) bis-ketoiminate using microwave heating

Preparation of ruthenium(iii) and rhodium(iii) tris-acetylacetonates and palladium(ii) bisketoiminate (Pd(i-acac)₂) under microwave irradiation using different synthetic conditions, both in the solid-phase and in solution, was studied with precise control of parameters. In the solid-phase systems, the preparation of the target product was hindered. The efficiency of the microwave heating increased when liquid phases of the reagent mixtures were used. For Pd(i-acac)₂, the highest yield was achieved under elevated temperature of the process, with the reaction time decreasing to several minutes. A laboratory procedure for the microwave synthesis of ruthenium(iii) and rhodium(iii) tris-acetylacetonates and palladium(ii) bis-ketoiminate in aqueous solutions was developed, which allowed us to obtain them in 85, 55, and 80% yields, respectively. These yields are higher than those reported in the literature, with the process becoming considerably less time consuming and laborious.     

The yjjN of E. coli codes for an l-galactonate dehydrogenase and can be used for quantification of l-galactonate and l-gulonate

Escherichia coli is able to utilize l-galactonate as a sole carbon source. A metabolic pathway for l-galactonate catabolism is described in E. coli, and it is known to be interconnected with d-galacturonate metabolism. The corresponding gene encoding the first enzyme in the l-galactonate pathway, l-galactonate-5-dehydrogenase, was suggested to be yjjN. However, l-galactonate dehydrogenase activity was never demonstrated with the yjjN gene product. Here, we show that YjjN is indeed an l-galactonate dehydrogenase having activity also for l-gulonate. The K _m and k _cat for l-galactonate were 19.5?±?0.6 mM and 0.51?±?0.03 s^?1, respectively. In addition, YjjN was applied for a quantitative detection of the both of these substances in a coupled assay. The detection limits for l-galactonate and l-gulonate were 1.65 and 10 μM, respectively.     

Sulfur-containing terpyridine derivatives: synthesis, coordination properties, and adsorption on the gold surface

Approaches to the synthesis of organic aurophilic ligands, viz., sulfur-containing 2,2′:6′,2’-terpyridine derivatives, were developed. Complexation reactions of the terpyridine ligands having thiophenol, diaryl disulfide, and alkyl aryl sulfide fragments with Co ⁱⁱ , Ni ⁱⁱ , and Rh ⁱⁱⁱ salts were studied. The structures of the coordination compounds obtained were established based on the elemental analysis data, density functional calculations, and electron spectroscopy. The structure of the complex of 4′-(4-methylsulfanyl)-2,2′:6′,2"-terpyridine with Ni(BF₄)₂ was also established by X-ray diffraction analysis. A method was proposed for the preparation of gold nanoparticle dimeric aggregates via coordination interactions of the ligands adsorbed on the gold nanoparticle surface with transition metal ions. A degree of nanoparticle aggregation upon their reaction with solutions of complex compounds of aurophilic nitrogen-containing ligands was determined by the concentration of the solution of the complex used.     

Bifidobacterium longum l-Arabinose Isomerase—Overexpression in Lactococcus lactis, Purification, and Characterization

Bifidobacterium longum NRRL B-41409 l-arabinose isomerase (l-AI) was cloned and overexpressed in Lactococcus lactis using a phosphate-depletion-inducible expression system. The purified B. longum l-AI was characterized using d-galactose and l-arabinose as the substrates. The enzyme was active and stable at acidic pH with an optimum at pH 6.0?C6.5. The enzyme showed the highest activity at 55?°C during a 20-min incubation at pH 6.5. The K _m value was 120?mM for l-arabinose and 590?mM for d-galactose. The V _max was 42?U mg^?1 with l-arabinose and 7.7?U mg^?1 with d-galactose as the substrates. The enzyme had very low requirement for metal ions for catalytic activity, but it was stabilized by divalent metal ions (Mg²⁺, Mn²⁺). The enzyme bound the metal ions so tightly that they could not be fully removed from the active site by EDTA treatment. Using purified B. longum l-AI as the catalyst at 35?°C, equilibrium yields of 36?% d-tagatose and 11?% l-ribulose with 1.67?M d-galactose and l-arabinose, respectively, as the substrates were reached.     

Efficient Microbial Conversion of l-Tyrosine to l-DOPA by Brevundimonas sp. SGJ

l-DOPA (3,4-dihydroxyphenyl-l-alanine), the most widely used drug for the treatment of Parkinson??s disease, was produced in buffer using biomass of Brevundimonas sp. SGJ. The effects of enhancers, such as carrageenan, diatomaceous earth, and activated charcoal, on the l-DOPA production were evaluated to obtain the maximum yield. The optimal process conditions found were pH?8, 2?g?l^?1 cell mass, 2?g?l^?1 l-tyrosine, 0.04?g?l^?1 CuSO₄, 0.02?g?l^?1 l-ascorbic acid, 0.5?g?l^?1 carrageenan, and 40?°C temperature. In addition, repeated use of cells resulted in the highest yield of 3.81?g?l^?1 (95.2%) of l-DOPA with utilization of 4?g?l^?1 l-tyrosine, and the highest tyrosinase activity (9,201?U?mg^?1) was observed at 18?h of incubation. Furthermore, the produced l-DOPA was confirmed by high-performance thin-layer chromatography, high-performance liquid chromatography, and gas chromatography?Cmass spectroscopy. Kinetic studies showed significant values of Y _p/s, Q _s, and q _s after optimization of the process. Thus, Brevundimonas sp. SGJ could be an eventual new source for large-scale production of l-DOPA.     

Studies on enzymatic oxidation of 3′,4′-dihydroxy-l-phenylalanine to dopachrome using kinetic isotope effect methods

We report the studies on the mechanism of oxidation of 3′,4′-dihydroxy-l-phenylalanine (l-DOPA) to neurotoxic dopachrome catalyzed by enzyme horseradish peroxidase (EC 1.11.1.7) using the kinetic (KIE), and solvent (SIE), isotope effect methods. For kinetic studies two specifically deuterated isotopomers: [2′,5′,6′-²H₃]-l -DOPA was synthesized by the acid catalyzed isotopic exchange between native l-DOPA and heavy water, and [5′-²H]-l-DOPA was synthesized in two step reaction. The first step involved acid catalyzed isotopic exchange between l-tyrosine and deuterated water and resulting product [3′,5′-²H₂]-l-tyrosine was hydroxylated by enzyme tyrosinase (EC 1.14.18.1). The values of deuterium KIEs and SIE’s in the enzymatic oxidation of l-DOPA and its isotopomers are determined using non-competitive spectrophotometric method. The measured values were: KIE on V _max (1.1 and 2.2) and KIE on V _max/K _M (1.7 and 3.2) for [2′,5′,6′-²H₃]-l-DOPA and [5′-²H]-l-DOPA, respectively, while the corresponding values of SIE were: SIE on V _max (2.1, 2.4, and 2.1) and SIE on V _max/K _M (1.3. 1.6, and 1.1) for l-DOPA, [2′,5′,6′-²H₃]-l-DOPA, and [5′-²H]-l-DOPA, respectively. The size of KIE and SIE, typical for secondary isotope effects indicate that both the solvent and presence of deuterium at the 2′-, 5′, and 6′-positions of l-DOPA has the little impact on the enzymatic oxidation of this compound.     

Synthesis and crystal structures of the heptafluoroacetylacetonatocopper(ii) and 4-iminoheptafluoropent-2-ene-2-aminatocopper(ii) complexes with triphenylphosphine oxide and pyridine

New chelate heptafluoroacetylacetonatocopper(ii) complexes with triphenylphosphine oxide and pyridine as well as the 4-iminoheptafluoropent-2-ene-2-aminatocopper(ii) complex with triphenylphosphine oxide were synthesized. The molecular and crystal structures of the complexes were studied by X-ray diffraction analysis. The reaction of 2-amino-4-imino-heptafluoropent-2-ene with CuO affords bis(4-imino-1,1,1,3,5,5,5-heptafluoropent-2-ene-2-aminato)copper(ii) in ～90% yield.     

Synthesis and complexing ability of 2-(2-ethoxycarbonyl-3-oxo-3-polyfluoroalkylprop-1-enylamino) benzoic acids

The condensation of ethyl 2-ethoxymethylidene-3-oxo-3-polyfluoroalkylpropionates with 2-aminobenzoic acid occurs at the ethoxymethylidene substituent and gives 2-(2-ethoxy-carbonyl-3-oxo-3-polyfluoroalkylprop-1-enylamino)benzoic acids. These compounds serve as new O,N,O-tridentate ligands capable of forming nickel(ii) and copper(ii) complexes.     

Diastereomeric P*-mono- and P*,P*-bidentate diamidophosphite ligands based on 1,4:3,6-dianhydro-d-mannitol in asymmetric metallocomplex catalysis

Synthesis of diastereomeric mono- and bidentate diamidophosphites bearing P*-stereo-centers and phosphabicyclo[3.3.0]octane backbone and their coordination with rhodium(i) and palladium(ii) are considered. Their use in Rh-catalyzed asymmetric allylation allowed one to achieve 87% ee values and the use in Rh-catalyzed asymmetric hydrogenation gave up to 98% ee.     

Synthesis of N-glycyl-β-glycopyranosyl amines,derivatives of natural oligosaccharides — glucose analogs of Lex antigen

Treatment of the natural tri-, tetra-, and pentasaccharides, β-d-Galp-(1→4)-[α-l-Fucp-(1→3)]-d-Glcp, α-l-Fucp-(1→2)-β-d-Galp-(1→4)-[α-l-Fucp-(1→3)]-d-Glcp, and α-l-Fucp-(1→2)-[α-d-GalNAcp-(1→3)]-β-d-Galp-(1→4)-[α-l-Fucp-(1→3)]-d-Glcp, which are glucose analogs of Le^x, with ammonium carbamate in aqueous methanol gave the corresponding β-glycopyranosyl amines. After their N-acylation with N-Z-glycine N-hydroxysuccinimidyl ester (Z is benzyloxycarbonyl) with subsequent hydrogenolytic removal of Z-group, corresponding N-glycyl-β-glycopyranosyl amines were obtained in yields up to 70%.     

Chiral resolution of l- and d-alanine and a racemic macrocyclic nickel(II) complex: synthesis and crystal structures

The reactions of a racemic four-coordinate Ni(II) complex [Ni(rac-L)](ClO₄)₂ with l- and d-alanine in acetonitrile/water gave two six-coordinate enantiomers formulated as [Ni(RR-L)(l-Ala)](ClO₄)·2CH₃CN (1) and [Ni(SS-L)(d-Ala)](ClO4) (2) (L = 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclo-tetradecane, Ala^? = alanine anion), respectively. Evaporation from the remaining solutions gave two four-coordinate enantiomers characterized as [Ni(SS-L)](ClO₄)₂ (S-3) and [Ni(RR-L)](ClO₄)₂ (R-3), respectively. Single-crystal X-ray diffraction analyses of complexes 1 and 2 revealed that the Ni(II) atom has a distorted octahedral coordination geometry, being coordinated by four nitrogen atoms of L in a folded configuration, plus one carboxylate oxygen atom and one nitrogen atom of l- or d-Ala^? in mutually cis-positions. Complexes 1 and 2 are supramolecular stereoisomers, constructed via hydrogen bonding between [Ni(RR-L)(l-Ala)]⁺ or [Ni(SS-L)(d-Ala)]⁺ monomers to form 1D hydrogen-bonded zigzag chains. The homochiral natures of complexes 1 and 2 have been confirmed by CD spectroscopy.     

Preparative Isolation and Purification of Flavonoids and Protocatechuic Acid from Sea Buckthorn Juice Concentrate (Hippophaë rhamnoides L. ssp. rhamnoides) by High-Speed Counter-Current Chromatography

High-speed counter-current chromatography (HSCCC)—a support free all liquid–liquid chromatography technique—has been successfully used for the preparative isolation of isorhamnetin 3-O-β-d-glucoside, isorhamnetin 3-O-β-rutinoside, quercetin 3-O-β-d-glucoside, syringetin 3-O-β-d-glucoside and protocatechuic acid from sea buckthorn juice concentrate (Hippophaë rhamnoides L. ssp. rhamnoides, Elaeagnaceae). The preparative HSCCC instrument was a multilayer coil planet centrifuge equipped with three preparative coils. Separation was performed with a two phase solvent system (n-hexane–n-butanol–water, 1:1:2 v/v/v) in ‘head-to-tail’ mode. Each injection of 4.1 g crude ethyl acetate extract yielded isorhamnetin 3-O-β-d-glucoside (95 mg), isorhamnetin 3-O-β-rutinoside (10 mg), quercetin 3-O-β-d-glucoside (5 mg), and protocatechuic acid (34 mg) with purities >98%. The flavonoid syringetin 3-O-β-d-glucoside (2 mg) was a novel compound for H. rhamnoides. Chemical structures of all compounds were determined by HPLC–ESI–MS–MS, 1D-NMR (¹H, ¹³C, DEPT 135) spectroscopy and for elucidation of glycosidic linkages 2D-NMR (HMBC) spectroscopy was used.     

Enzymatic Oxidation and Separation of Various Saccharides with Immobilized Glucose Oxidase

Glucose oxidase from Aspergillus niger, the specific enzyme for β-d-glucose oxidation, can also oxidize other related saccharides at very slow or negligible rates. The present study aimed to compare the kinetics of d-glucose oxidation using immobilized glucose oxidase on bead cellulose for the oxidation of related saccharides using the same biocatalyst. The significant differences were observed between the reaction rates for d-glucose and other saccharides examined. As a result, k _cat/K _M ratio for d-glucose was determined to be 42 times higher than d-mannose, 61.6 times higher than d-galactose, 279 times higher than d-xylose, and 254 times higher than for d-fructose and d-cellobiose. On the basis of these differences, the ability of immobilized glucose oxidase to remove d-glucose from d-cellobiose, d-glucose from d-xylose, and d-xylose from d-lyxose was examined. Immobilized catalase on Eupergit and mixed with immobilized glucose oxidase on bead cellulose or co-immobilized with glucose oxidase on bead cellulose was used for elimination of hydrogen peroxide from the reaction mixture. The accelerated elimination of d-glucose and d-xylose in the presence of co-immobilized catalase was observed. The co-immobilized glucose oxidase and catalase were able to decrease d-glucose or d-xylose content to 0–0.005% of their initial concentrations, while a minimum decrease of low oxidized saccharides d-xylose, d-cellobiose, and d-lyxose, respectively, was observed.     

RP-LC Resolution of (R,S)-Atenolol via Diastereomerization with Marfey’s Reagent and Its Structural Variants Under Conventional and Microwave Heating

(R,S)-Atenolol was derivatized with Marfey’s reagent, (MR; 1-fluoro-2,4-dinitrophenyl-5-l-alanine amide or FDNP-l-Ala-NH₂) and its four structural variants (FDNP-l-Phe-NH₂, FDNP-l-Val-NH₂, FDNP-l-Leu-NH₂ and FDNP-l-Pro-NH₂). MR reacts quantitatively with 1° and 2° amino groups and atenolol has a secondary amino group. The derivatization reactions were carried out under conventional and microwave heating and compared. The resulting diastereomers were separated on RP-TLC and on a C18 column with detection at 340 nm. (R)-Isomer eluted before (S). The conditions of derivatization and chromatographic separation were optimized. The method was validated for linearity, repeatability, limits of detection and limit of quantification.