A multiresidue analytical method using solid-phase extraction and high-pressure liquid chromatography tandem mass spectrometry to measure pharmaceuticals of different therapeutic classes in urban wastewaters

An analytical method with two extraction steps has been developed and validated for the simultaneous determination of 30 pharmaceuticals belonging to various therapeutic categories in urban wastewater. The aim was to boost the little available information on drugs' fates in sewage treatment plants (STPs) and in the receiving surface water. Aqueous samples were divided into two aliquots, each extracted by a different solid-phase extraction (SPE) method and analysed by reversed-phase liquid chromatography tandem mass spectrometry (HPLC-MS-MS). Recoveries of the pharmaceuticals were mostly greater than 70% and the overall variability of the method was below 8%. The instrumental quantification limit (IQL) varied between 30 and 400 pg injected, and the limits of quantification (LOQ) were in the low ng/L range. Nineteen pharmaceuticals were detected in concentrations between 0.5 and 2000 ng/L in effluents collected from several STPs in Italy. Atenolol, ciprofloxacin, furosemide, hydrochlorothiazide, ofloxacin, ranitidine and sulphamethoxazole were the most abundant compounds. The present analytical method was useful to check for pharmaceuticals in various Italian STPs and to identify the most abundant compounds.     

Reaction of alkynes with iodine monochloride revisited

6-Exo-dig and/or 7-endo-dig iodocyclization reactions of functionalized acetylenic derivatives with ICl are disfavored in comparison with the corresponding electrophilic addition reactions providing regioselectively (E)-1-chloro-2-iodoethene derivatives. On the contrary, 6-endo-digand 5-exo-dig iodocyclizations of methyl ynoates with ICl seem to be favored in comparison with the corresponding electrophilic addition reactions.     

Synthesis of 2-substituted 1,3-butadienyl compounds by palladium-catalyzed regioselective 1,2-elimination reaction of methylvinylcarbinol acetates

Alkylation of the dianion of 3-methyl-3-buten-2-ol, followed by acetylation and palladium-catalyzed 1,2-elimination reaction of the so obtained methylvinylcarbinol acetates allows to synthesize regioselectively 2-substituted 1,3-butadienyl compounds having high isomeric purity.     

Intramolecular Dynamics of Tetranuclear Iridium Carbonyl Cluster Compounds. Part V. Polysubstituted derivatives of [Ir4(CO)12]

The dynamic behaviour of twelve polysubstituted derivatives of [Ir₄(CO)₁₂] has been investigated in solution, using 2D-EXSY, and VT-³¹P- and ¹³C-NMR. [Ir₄(CO)₆(μ₂-CO)₃(η⁴-diarsine) PPh₃] and [Ir₄(CO)₆(μ₂-CO)₃(η⁴-nor-bornadiene)(PMePh₂)] exhibit two isomeric forms in solution, which interconvert through an intramolecular change of basal face. The related cluster [Ir₄(CO)₆(μ₂-CO)₃(η⁴-norbornadiene)PPh₃] exists as a single isomer in solution. It displays rotation of CO ligands about the apical Ir-atom, followed by two consecutive changes of basal face. The tetrasubstituted clusters with two chelating ligands [Ir₄(CO)₅(μ₂-CO)₃(η⁴-diolefin)₂] also exhibit rotation of apical CO's, the activation energy increases with greater steric hindrance of the radical ligands. A quantitative analysis of the ³¹P- and ¹³C-2D-EXSY spectra followed by simulation of the corresponding VT-NMR spectra of [IR₄(CO)₅(μ₂-CO)₃(μ₂-L)₂] (L = bis(diphenylphosphino)methane and 1,3-bis(diphenylphosphino)propane) revealed a pairwise averaging of the P-atoms, caused by two parallel changes of basal face averaging all CO ligands. In addition, the restricted rotation of ligands about the apical Ir-atom was identified at higher temperatures. The remaining clusters are either rigid on the NMR time scale, or display CO-scrambling about a single Ir-atom.     

Production of Enzymes by Plant Cells Immobilized by Sol-Gel Silica

Ajuga reptans cells are cultivated and used for production of invertase. These plant cells are immobilized by a sol-gel SiO₂ membrane, which is built up directly on the cell surface by exposure to a gaseous flow of silicon alcoxide precursors. The immobilization modifies the metabolic activity of cells, resulting in a 40-fold increase in invertase production with respect of free cells. Results concerning total release of proteins, cell growth and produced invertase activity are discussed, considering the absence of breeding, induced by SiO₂ immobilization, the prominent factor promoting the observed exceptional increase in invertase productivity.     

Theoretical investigations on the solvation process

The conformation energies for monohydrated associates M · H₂O, where M stands for oxirane, aziridine, oxaziridine and cyclopropene, have been obtained by using an electrostatic method, tested in a preceding paper, which relies on SCF molecular potentials calculated exactly. Stable associates have been found in the heterogroup region as well as near the bent bonds (single or double).A discussion is made on the errors in calculating thermodynamic properties for such associates in gas phase by using a priori calculations. As a numerical example the free energy change in the association process is compared for two monohydrated associates of aziridine.

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Zusammenfassung Die Konformationsenergien für Anlagerungsverbindung M · H₂O, wobei M für Oxiran, Aziridin, Oxaziridin und Cyclopropen steht, werden mit einer elektrostatischen Methode berechnet. Dieses Verfahren wurde in einer vorhergehenden Veröffentlichung getestet und beruht auf exakt berechneten SCF-Molekülpotentialen. Stabile Anlagerungsverbindungen wurden für Konformationen gefunden, bei denen das Wassermolekül in der Nähe der Heterogruppe oder der gezogenen Einfach- oder Doppelbindung liegt. Die Fehler bei der Berechnung thermodynamischer Eigenschaften für derartige Anlagerungsverbindungen in der Gasphase werden abgeschätzt. Als ein numerisches Beispiel wird die Differenz der freien Energie bei der Anlagerung für zwei Anlagerungsverbindungen von Aziridin und Molekül Wasser verglichen.

     

First general approach to cyclohex-3-ene-1,1-bis(phosphonates) by Diels-Alder cycloaddition of tetraethyl vinylidenebis(phosphonate) to 1,3-dienes

Tetraethyl vinylidenebis(phosphonate) (VBP) reacts smoothly with substituted 1,3-dienes at 90-110 degrees C without solvent to give the corresponding cyclohex-3-ene-1,1-bis(phosphonates) in good yields (60-85%). With nonsymmetrically substituted dienes, mixtures of regioisomers are obtained, the regioisomeric ratio being exclusively controlled by electronic effects. Danishefsky's diene allows tetraethyl 4-oxocyclohex-2-ene-1,1-bis(phosphonate) to be obtained in an 81% overall yield after the acid-catalyzed hydrolysis of the Diels-Alder cycloadduct. With 2,3-dimethoxy-1,3-butadiene, a mixture of regioisomeric dimethoxycyclohexene-1,1-bis(phosphonates) is formed by the VBP-catalyzed isomerization of the normal Diels-Alder cycloadduct. The mixture converges into tetraethyl 3,4-dimethoxycyclohex-2-ene-1,1-bis(phosphonate) at prolonged reaction times.     

Ethanol decomposition: C--C cleavage selectivity on Rh(111).

Ethanol adsorption, desorption and decomposition on Rh(111) have been studied by X-ray photoelectron spectroscopy and tem-perature-programmed desorption experiments. The evolution of the C is and O is core level spectra was monitored as a function of ethanol exposure and surface temperature. Ethanol adsorption at 90 K results in two nonequivalent ethanol-adsorbed species at low surface coverage, while a third species--related to multilayer formation--appears after longer exposures. Upon surface annealing, ethanol undergoes both desorption and dissociation, thus creating intermediate surface species which further decompose to hydrogen, carbon monoxide and atomic carbon. Our results clearly show that C--C bond cleavage is the preferential dissociation channel, while C--O bond scission is not observed. Calculations performed within the framework of the unity bond index-quadratic exponent potential model, have been used to test and compare different competing dissociation channels, providing an estimate of adsorption energies and dissociation barriers.     

Synthesis,Reactivity, and Fluxional Behaviour of [Ir2Rh2(CO)12], and Crystal Structure of [Ir2Rh2(CO)8(norbornadiene)2]

The synthesis of [Ir₂Rh₂(CO)₁₂] ( 1 ) by the literature method gives a mixture 1 /[IrRh₃(CO)₁₂] which cannot be separated using chromatography. The reaction of [Ir(CO)₄]^? with 1 mol-equiv. of [Rh(CO)₂(THF)₂]⁺ in THF gives pure 1 in 61% yield. Crystals of 1 are highly disordered, unlike those of its derivative [Ir₂Rh₂(CO)₅(μ₂-CO)₃(norbornadiene)₂] which were analysed using X-ray diffraction. The ground-state geometry of 1 in solution has three edge-bridging CO's on the basal IrRh₂ face of the metal tetrahedron. Time averaging of CO's takes place above 230 K. The CO site exchange of lowest activation energy is due to one synchronous change of basal face, as shown by 2D- and VT-¹³C-NMR. Substitution of CO by X^? in 1 takes place at a Rh-atom giving [Ir₂Rh₂(CO)₈(μ₂-CO)₃X]^? (X = Br, I). Substitution by bidentate ligands gives [Ir₂Rh₂(CO)₇(μ₂-CO)₃(η⁴-L)] (L = norbornadiene, cycloocta-1,5-diene) where the ligand L is chelating a Rh-atom of the basal IrRh₂ face. Carbonyl substitution by tridentate ligands gives [Ir₂Rh₂(CO)₆(μ₂-CO)₃(μ₃-L)] (L = 1,3,5-trithiane, tripod) with L capping the triangular basal face of the metal tetrahedron. Carbonyl scrambling is also observed in these substituted derivatives of 1 and is mainly due to the rotation of three terminal CO's about a local C₃ axis on the apical Ir-atom.     

Synthetic approach to substituted cyclopropanes based on the coupling reaction of lithiated chloroalkyloxazolines with Fischer carbene complexes

Regioselective addition of lithiated oxazoline 2a, easily available from 2-(1-chloroethyl)-4,4-dimethyl-2-oxazoline 1a (LDA, THF, -98 degrees C), to alpha,beta-unsaturated Fischer carbene complexes 3 afforded cyclopropylcarbene complexes 4 as sole diastereoisomers. Exposure of carbene complexes 4a-c (M = Cr) to air and sunlight gave cyclopropane carboxylate derivatives 5a-c. A plausible mechanistic explanation is proposed. Moreover, when lithiated oxazoline 2b was generated from 1b in the presence of the carbene complex 3a,b, the oxazolinylcyclopropane carboxylates 6a,b formed as a 1:1 mixture of diastereoisomers. Chiral lithiated oxazoline 2c added regioselectively and diastereoselectively to chromium complexes 3a,b and to tungsten complexes 3d,e, leading, after oxidation of the metal fragment, to esters 7a,b with good diastereoselectivity (dr = 4:1). The reaction of lithiated oxazoline 2d with chromium complex 3b and tungsten complex 3e proceeded less diastereoselectively, furnishing, in both cases, after oxidation, the ester 7c as a 3:2 diastereoselective mixture.