Gas chromatography–tandem mass spectrometry analysis of 52 monohydroxylated metabolites of polycyclic aromatic hydrocarbons in hairs of rats after controlled exposure

A method based on gas chromatography–tandem mass spectrometry after derivatization with N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide was developed for the analysis of monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) in hair. The method focused on 52 target compounds corresponding to two- to six-ring monohydroxylated metabolites of polycyclic aromatic hydrocarbons (PAHs). The limits of quantification ranged from 0.2 to 50 pg mg^?1. The method was then applied to the analysis of hair samples collected from rats exposed to 12 PAHs at 0.01, 0.1, and 1 mg kg^?1, by intraperitoneal injection, for 28 days. The results of this study confirm that these metabolites can be incorporated in hair after intraperitoneal administration of the corresponding parent compound. Only 20 of the 52 metabolites were actually detected in hair samples and corresponded to nine parent PAHs. The mean concentrations of OH-PAHs in rat hair samples exposed to PAHs at 1 mg kg^?1 ranged from 0.6?±?0.2 pg mg^?1 for 8-hydroxybenzo[b]fluoranthene to 6.7?±?1.0 pg mg^?1 for 1-hydroxypyrene. The results also demonstrated that hair pigmentation has no influence on the concentration of most OH-PAHs. This animal experiment confirmed the incorporation of PAH metabolites in hair and demonstrated that the method was sufficiently sensitive to detect low levels of exposure to PAHs. These results confirmed the usefulness of hair analysis in the biomonitoring of human exposure to PAHs.

High stereocontrol in aldol reaction with ketones: enantioselective synthesis of beta-hydroxy gamma-ketoesters by ester enolate aldol reactions with 2-acyl-2-alkyl-1,3-dithiane 1-oxides

The asymmetric aldol reaction of 1,2-diketones, masked as nonracemic 2-acyl dithiane oxides, with lithium enolates derived from several esters and lactones, proceeds with a high degree of stereocontrol at both carbonyl and enolate prochiral centers, the stereocontrol mainly determined by the configuration of the sulfoxide sulfur atom. The sense of induced stereochemistry observed for ester enolates is different from that seen for lactone enolates. Hydrolysis of the dithiane oxide units of the major diastereoisomerically pure aldol products affords enantiomerically pure tertiary alpha-substituted beta-hydroxy-gamma-ketoesters.     

Determination of hydroxylated metabolites of polycyclic aromatic hydrocarbons in human hair by gas chromatography–negative chemical ionization mass spectrometry

The study describes the determination of mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs), metabolites of PAHs, in human hair. Twelve selected OH-PAHs from two to four rings, generally determined in urine analysis, were investigated as markers of human exposure to PAHs. Following hydrolysis of hair specimens of 50–300 mg with 1 M NaOH, OH-PAHs were extracted using dichloromethane and submitted to an optimized derivatization with (2S,4R)-N-heptafluorobutyryl-4-heptafluorobutoyloxy-prolyl chloride. Compounds were then analyzed using gas chromatography–negative chemical ionization mass spectrometry (GC–NCIMS). The average inter-day and intra-day variability was 12% and 17%, respectively. The average recovery was 52% and the limits of detection and quantification ranged from 20 and 66 pmol/g for 1-OH-phenanthrene (i.e., 3.9 and 12.8 pg/mg) to 311 and 1030 pmol/g for 2-OH-benzo(c)phenanthrene (i.e., 75.9 and 251 pg/mg). The influence of hair washing with water as decontamination step, and enzymatic treatment (β-glucuronidase) to hydrolyze conjugated derivatives were also tested. The application of the developed method to the analysis of 30 hair specimens (17 from non-smoker and 13 from smoker volunteers) demonstrated inter-individual qualitative and quantitative variations. According to the easiness of hair sampling and based on the extended detection windows provided by hair analysis, this method is proposed as a new promising tool for the assessment of human chronic exposure to PAHs.     

Radical cyclization cascades of unsaturated Meldrum's acid derivatives

Unsaturated, differentially substituted Meldrum's acid derivatives undergo cascade cyclizations upon ester reduction with SmI(2)-H(2)O. The cascade cyclizations proceed in good yield and with high diastereocontrol and convert simple, achiral starting materials to complex molecular architectures, bearing up to four stereocenters, in a single operation. The cascades are triggered by the generation and trapping of unusual radical-anions formed by electron transfer to the ester carbonyl.     

Electrochemical Synthesis and Characterisation of Alternating Tripyridyl–Dipyrrole Molecular Strands with Multiple Nitrogen‐Based Donor–Acceptor Binding Sites

Synthesis of alternating pyridine–pyrrole molecular strands composed of two electron‐rich pyrrole units (donors) sandwiched between three pyridinic cores (acceptors) is described. The envisioned strategy was a smooth electrosynthesis process involving ring contraction of corresponding tripyridyl–dipyridazine precursors. 2,6‐Bis[6‐(pyridazin‐3‐yl)]pyridine ligands 2 a – c bearing pyridine residues at the terminal positions were prepared in suitable quantities by a Negishi metal cross‐coupling procedure. The yields of heterocyclic coupling between 2‐pyridyl zinc bromide reagents 12 a – c and 2,6‐bis(6‐trifluoromethanesulfonylpyridazin‐3‐yl)pyridine increased from 68 to 95 % following introduction of electron‐donating methyl groups on the metallated halogenopyridine units. Favorable conditions for preparative electrochemical reduction of tripyridyl–dipyridazines 2 b , c were established in THF/acetate buffer (pH 4.6)/acetonitrile to give the targeted 2,6‐bis[5‐(pyridin‐2‐yl)pyrrol‐2‐yl]pyridines 1 b and 1 c in good yields. The absorption behavior of the donor–acceptor tripyridyl–dipyrrole ligands was evaluated and compared to theoretical calculations. Highly fluorescent properties of these chromophores were found (ν_em≈2×10⁴ cm^?1 in MeOH and CH₂Cl₂), and both pyrrolic ligands exhibit a remarkable quantum yield in CH₂Cl₂ (?_f=0.10). Structural studies in the solid state established the preferred cis conformation of the dipyrrolic ligands, which adopting a planar arrangement with an embedded molecule of water having a complexation energy exceeding 10 kcal mol^?1. The ability of the tripyridyl–dipyrrole to complex two copper(II) ions in a pentacoordinate square was investigated.     

Supramolecular isomerism in multivalent metal-templated assemblies with topochemical influence in the regioselective synthesis of tetrakis(2-pyridyl)cyclobutane isomers

An unprecedented example of supramolecular isomerism based on 2D hydrogen-bonded multi-component networks that leads to the preparation of different photoproducts via a topochemical transformation is reported.     

Long-range effects on the capture and release of a chiral guest by a helical molecular capsule

Helically folded molecular capsules based on oligoamide sequences of aromatic amino acids which are capable of binding tartaric acid in organic solvents with high affinity and diastereoselectivity have been synthesized, and their structures and binding properties investigated by (1)H NMR, X-ray crystallography, circular dichroism, and molecular modeling. We found that elongating the helices at their extremities by adding monomers remote from the tartaric binding site results in a strong increase of the overall helix stability, but it does not influence the host-guest complex stability. The effect of this elongation on the binding and release rates of the guest molecules follows an unexpected non-monotonous trend. Three independent observations (direct monitoring of exchange over time, 2D-EXSY NMR, and molecular modeling) concur and show that guest exchange rates tend to first increase upon increasing helix length and then decrease when helix length is increased further. This investigation thus reveals the complex effects of adding monomers in a helically folded sequence on a binding event that occurs at a remote site and sheds light on possible binding and release mechanisms.     

Isosteric Substitutions of Urea to Thiourea and Selenourea in Aliphatic Oligourea Foldamers: Site‐Specific Perturbation of the Helix Geometry

Nearly isosteric oxo to thioxo substitution was employed to interrogate the structure of foldamers with a urea backbone and explore the relationship between helical folding and hydrogen‐bonding interactions. A series of oligomers with urea bonds substituted by thiourea bonds at discrete or all positions in the sequence have been prepared and their folding propensity was studied by using a combination of spectroscopic methods and X‐ray diffraction. The outcome of oxo to thioxo replacements on the helical folding was found to depend on whether central or terminal ureas were modified. The canonical helix geometry was not affected upon insertion of thioureas close to the negative end of the helix dipole, whereas thioureas close to the positive pole were found to increase the terminal flexibility and cause helix fraying. Perturbation was amplified when a selenourea was incorporated instead, leading to a structure that is only partly folded.     

Etude structurale de l'hydruro-oxyde LaHO par diffraction des rayons X et par diffraction des neutrons

The hydride-oxide LaHO crystallizes with a fluorite superstructure. The unit cell is tetragonal, space group $\text{P4}\text{nmm}\text{, a = 8,074(1)}$ Å, c = 5,739(1) Å, and Z = 8. The structure has been determined by two complementary techniques: X-ray and neutron diffraction. The La³⁺ ions are situated in the center of cubes at the corners of which four O^2? and four H^? are placed, there exist three different types of environment according to the distribution of the two anion species (the anions of the same type form either a tetrahedron or occupy a face or a diagonal plane of the cube). The LaO(H) distances observed are discussed by taking into account the relationship which exists between bond strength and bond length. The average value of d 〈OH〉 is 2,85 Å, which is rather unusual. It confirms that we are indeed dealing with a hydride-oxide simultaneously associating the O^2? and H^? ions in a ternary combination. Through energy considerations (electrostatic site potential and lattice potential), the structural arrangement of LaHO is compared to that encountered in the case of the homologous lanthanum oxifluorides.