Enantioselective synthesis of (R)- and (S)-N-Boc-morpholine-2-carboxylic acids by enzyme-catalyzed kinetic resolution: application to the synthesis of reboxetine analogs

The (R)- and (S)-N-Boc-morpholine-2-carboxylic acids 9 and 10 were prepared using an enantioselective synthesis employing a highly selective enzyme-catalyzed kinetic resolution of racemic n-butyl 4-benzylmorpholine-2-carboxylate (11) as the key step. Acids 9 and 10 were then converted efficiently and stereoselectively to reboxetine analogs 3 and 4.     

Microwave-induced by-products in the synthesis of 2-(4-methyl-2-phenylpiperazinyl)pyridine-3-carbonitrile

The Letter describes the investigation of an industrial reaction of N-methylphenylpiperazine and chloronicotinonitrile, under microwave heating. Besides the formation of the expected 2-(4-methyl-2-phenylpiperazinyl)pyridine-3-carbonitrile (4), extension of the scale leads to unexpected by-products. A specific pathway due to the formation of a reactive ‘ionic alkylating intermediate’ formed in situ under microwave conditions is proposed to explain the results observed.     

The important effect of ligand architecture on the selectivity of metal ion recognition in An(III)/Ln(III) separation with N-donor extractants

The existence of a strong correlation between ligand architecture and metal ion binding selectivity is demonstrated through large differences in the separation efficiencies found in the selective extraction of Am3+ from an acidic mixture of Am3+ and Eu3+ for three new tetrapodal hexadentate ligands containing four 2-pyrazinylmethyl groups attached to three different diamino spacers.     

High-power and superpower Cerenkov masers

The linear and nonlinear theory of the efficient operation of high-power (gigawatt) and superpower (50 GW) Cerenkov masers is presented. Issues such as breakdown, plasma production, and coupling to the output device are discussed. The relative merits of dielectric Cerenkov masers and plasma Cerenkov masers are considered. The principal design tool is a new particle simulation model that was developed to investigate Cerenkov masers. The novel aspects of this model are briefly described along with a comparison of calculated and experimental results. The agreement between calculations and measurements is generally good. Designs for a high-power and superpower plasma Cerenkov masers are also described     

Comparative structural studies of iodide complexes of uranium(III) and lanthanide(III) with hexadentate tetrapodal neutral N-donor ligands

The syntheses, the solution structures, and the crystal structures of the two new tetrapodal N-donor ligands N,N,N',N'-tetrakis(2-pyrazylmethyl)-1,3-trimethylenediamine (tpztn), 1, and N,N,N',N'-tetrakis(2-pyrazylmethyl)-trans-1,2-cyclohexanediamine (tpzcn), 2, are described. Two different geometric isomers of the cation [La(tpztn)I(2)](+) were isolated in which the ligand adopts two different conformations leading to strong differences in the metal-ligand bond distances. The crystal structure of isostructural complexes of La, U, Ce, and Nd were determined by X-ray diffraction studies for the ligands tpztn and tpzcn. In both series of complexes the two methylpyrazyl arms and the diamine spacer (trimethylene or cyclohexane) around each aliphatic nitrogen adopt the same helical configuration. The complexes crystallize as a racemic mixture of Lambda,Lambda and Delta,Delta enantiomers with distorted square antiprism geometries. In these complexes the M-N(pyrazine) distances show a decrease from La to Ce and from La to Nd which corresponds well to the decrease in ionic radius as expected in a purely ionic bonding model. Conversely the mean value of the U-N(pyrazine) distances is shorter (0.043(3) A for tpztn and 0.054(11) A for tpzcn) than the mean value of the La-N(pyrazine) distances. These differences are significantly larger than the decrease expected from the variation of the ionic radii and can be interpreted in terms of a stronger M-N interaction for U(III). Previously reported extraction studies have shown that while the tripod tris[(2-pyrazyl)methyl]amine (tpza) containing three pyrazyl nitrogens extracts An(III) preferentially to Ln(III), tpztn and tpzcn display no selectivity despite the presence of four pyrazyl groups connected to a different spacer. The structural studies described here show that despite the lack of selectivity observed in the extraction conditions, the arrangement of pyrazyl nitrogens in the tetrapodal architectures of tpztn and tpzcn allows for metal-ligand interaction similar to that observed for tpza.     

Fe3+-hydroxide ligation in the superoxide reductase from Desulfoarculus baarsii is associated with pH dependent spectral changes

Superoxide reductase (SOR) catalyzes the reduction of O2*- to H2O2. Its active site consists of a non-heme Fe2+ center in an unusual square-pyramidal [His4 Cys] coordination. Like many SORs, the electronic absorption band corresponding to the oxidized active site of the SOR from Desulfoarculus baarsii exhibits a pH-dependent alkaline transition changing from ca. 644 to 560 nm as the pH increases and with an apparent pKa of 9.0. Variants in which the conserved amino acids glutamate 47 and lysine 48 were replaced by the neutral residues alanine (E47A) and isoleucine (K48I), respectively, exhibited the same alkaline transition but at lower apparent pKa values of 6.7 and 7.6, respectively. Previous work [Nivière, V.; Asso, M.; Weill, C. O.; Lombard, M.; Guigliarelli, B.; Favaudon, V.; Houée-Levin, C. Biochemistry 2004, 43, 808-818] has shown that this alkaline transition is associated with the protonation/deprotonation of an unidentified base, B-, which is neither E47 nor K48. In this work, we show by resonance Raman spectroscopy that at basic pH a high-spin Fe3+-OH species is formed at the active site. The presence of the HO- ligand was directly associated with an absorption band maximum at 560 nm, whereas upon protonation, the band shifts to 644 nm. With respect to our previous work, B- can be identified with this high-spin Fe3+-OH species, which upon protonation results in a water molecule at the active site. Implications for the SOR catalytic cycle are proposed.     

Solid-state and solution properties of cationic lanthanide complexes of a new neutral heptadentate N4O3 tripodal ligand

The synthesis of the potentially heptadentate ligand tris[6-((2-N,N-diethylcarbamoyl)pyridyl)methyl]amine, tpaam, containing three pyridinecarboxamide arms connected to a central nitrogen is described. Lanthanide complexes of this ligand are prepared and characterized. The crystallographic structure of the complexes of three lanthanide ions (La, Nd, Lu) is determined. The lanthanide(III) complexes of tpaam crystallize as monomeric species (in the presence of chloride or iodide counterions) in which the ligand tpaam acts as a N4O3 donor. The crystal structures presented here show that the Ln[bond]O and Ln[bond]N(pyridyl) distances in the complexes of tpaam are similar to those found for the tpaa complexes (H(3)tpaa = alpha,alpha',alpha' '-nitrilotri(6-methyl-2-pyridinecarboxylic acid) despite the difference in charge. A lengthening of the Ln[bond]N(apical) distance is observed in the tpaam complexes compared to the tpa (tris[(2-pyridyl)methyl]amine) complexes which is more marked for larger lanthanides than for smaller ones. The solution structures of the tpaam complexes were analyzed across the 4f series and compared to the solution structures of the lanthanide complexes of the tetradentate ligand tpa. Proton NMR studies are in agreement with the presence of C(3)(v) symmetric solution species for both ligands. For the larger lanthanides, the cation moves away from the apical nitrogen compared to the position occupied in tpa complexes, whereas for the smaller lanthanides, the metal ion is located in a similar position for the two ligands. Quite surprisingly, the formation constant of the Eu(tpaam)Cl(3) complex in D(2)O at 298 K (log beta(110) = 2.34(4)) is very similar to the one reported for Eu(tpa)Cl(3) (log beta(110) = 2.49(4) at 298 K in D(2)O) indicating that the addition of three amide groups to the ligand tpa does not lead to any increase in stability of the lanthanide complexes of tpaam compared to those of tpa.     

Polymer bilayer formation due to specific interactions between beta-cyclodextrin and adamantane: a surface force study

The purposes of this study are to utilize the interactions between an adamantane end-capped poly(ethylene oxide) (PEO) and a cationic polymer of beta-cyclodextrin to build polymer bilayers on negatively charged surfaces, and to investigate the interactions between such layers. The association of this system in solution has been studied by rheology, light scattering, and fluorescence measurements. It was found that the adamantane-terminated PEO (PEO-Ad) mixed with the beta-cyclodextrin polymer gives complexes where the interpolymer links are formed by specific inclusion of the adamantane groups in the beta-cyclodextrin cavities. This results in a higher viscosity of the solution and growth of intermolecular clusters. The interactions between surfaces coated with a cationized beta-cyclodextrin polymer across a water solution containing PEO-Ad polymers were studied by employing the interferometric surface force apparatus (SFA). In the first step, the interaction between mica surfaces coated with the cationized beta-cyclodextrin polymer in pure water was investigated. It was found that the beta-cyclodextrin polymer adsorbs onto mica and almost neutralizes the surface charge. The adsorbed layers of the beta-cyclodextrin polymer are rather compact, with a layer thickness of about 60 A (30 A per surface). Upon separation, a very weak attractive force is observed. The beta-cyclodextrin solution was then diluted by pure water by a factor of 3000 and a PEO-Ad polymer was introduced into the solution. Two different architectures of the PEO-Ad polymer were investigated: a four-arm structure and a linear structure. After the adsorption of the PEO polymer onto the beta-cyclodextrin layer reached equilibrium, the forces were measured again. It was found that the weak repulsive long-range force had disappeared and an attractive force caused the surfaces to jump into contact, and that the compressed layer thickness had increased. The attractive force is interpreted as being due to a specific recognition between the hydrophobic adamantane groups on the PEO-Ad polymer and the hydrophobic cavity in the beta-cyclodextrin molecules. Furthermore, the attractive force observed on separation has increased significantly, which is a further indication of a specific interaction between the beta-cyclodextrin polymer and the adamantane groups.     

Simultaneous analysis of cadmium, lead, mercury, and arsenic content in foodstuffs of animal origin by inductively coupled plasma/mass spectrometry after closed vessel microwave digestion: method validation

A method validation of the total analysis of cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg) in foodstuffs by inductively coupled plasma/mass spectrometry (ICP/MS) after closed vessel microwave digestion is presented. Due to the lack of reference method for ICP/MS techniques in food and, based on the project of the European Committee of Normalization (CEN/TC 275/WG 10), the Agence Fran?aise de Normalisation (AFNOR) guidelines NF V03-110 were used for the evaluation of this method based on 2 steps, sample preparation and multielement detection. Several criteria considered as compulsory (linearity, specificity, precision under repeatability conditions, and trueness) have been estimated and discussed, in addition to intermediate precision reproducibility, the limit of detection, and the limit of quantification. Furthermore, a comparison with in-house methods using electrothermal atomic absorption was performed using an external proficiency testing scheme and food samples. The results indicated that this method could be used in the laboratory for the routine determination of these 4 cumulative toxic metals in foodstuffs with acceptable analytical performance.     

Study of tryptophan enantiomer binding to a teicoplanin-based stationary phase using the perturbation technique. Investigation of the role of sodium perchlorate in solute retention and enantioselectivity

The retention of D,L-tryptophan enantiomers on an immobilized teicoplanin column was investigated in relation to the mobile phase sodium perchlorate concentration using the perturbation method to determine the solute distribution isotherms. From the experimental data, it appeared that the bi-Langmuir model was able to describe D- and L-enantiomer retention on the immobilized selector over the salt concentration range. An increase in the apparent enantioselectivity with an increase in sodium perchlorate concentration was observed. The chiral recognition enhancement was governed by (i) an increase in the difference of the adsorption constants for binding to the high-affinity site (aglycone pocket) between the two enantiomers and (ii) enhancement of the number of aglycone chiral regions interacting with D-tryptophan. It is suggested that an ion-pair formation mechanism between perchlorate and solute and/or selector is responsible for this behavior. In addition, this work shows that additional secondary sites on the teicoplanin surface are involved in the apparent enantioselectivity at low sodium perchlorate concentrations.