Detection of β-methylphenethylamine,a novel doping substance,by means of UPLC/MS/MS

Novel substances of expected doping activity are constantly introduced to the market. β-Methylphenethylamine (BMPEA) is classified as a doping agent by the World Anti-Doping Agency as it is a positional isomer of amphetamine. In this work, the development and application of a simple and rapid analytical procedure that enables discrimination between both isomers is described. The analytes of interest were extracted from urine by a two-step liquid–liquid extraction and then analyzed by UPLC/MS/MS under isocratic conditions. The entire analytical procedure was validated by evaluating its selectivity, discrimination capabilities, carry-over, sensitivity, and influence of matrix effects on its performance. Application of the method resulted in detection of BMPEA in eight anti-doping samples, including the first report of adverse analytical finding regarding its use. Further analysis showed that BMPEA may be eliminated unchanged along with its phase II conjugates, the hydrolysis of which may considerably improve detection capabilities of the method. Omission of the hydrolysis step may therefore, produce false-negative results. Testing laboratories should also carefully examine their LC/MS/MS-based amphetamine and BMPEA findings as both isomers fragment yielding comparable collision-induced dissociation spectra and their insufficient chromatographic separation may result in misidentification. This is of great importance in case of forensic analyses as BMPEA is not controlled by the public law, and its manufacturing, distribution, and use are legal.     

Solid–liquid equilibria of acenaphthene with o-, m-, or p-dichlorobenzene

A differential scanning calorimetry (DSC) was used to determine binary solid–liquid equilibria (SLE) for acenaphthene  + o-dichlorobenzene, +m-dichlorobenzene, and +p-dichlorobenzene over the whole concentration range. It was found that all systems are simple eutectic systems. The eutectic point of the (acenaphthene + o-dichlorobenzene) system is at 254.95 K and 0.0334 mole fraction of acenaphthene, that of the (acenaphthene + m-dichlorobenzene) system at 246.15 K and 0.0460 mole fraction of acenaphthene and that of the (acenaphthene + p-dichlorobenzene) system at 307.75 K and 0.2940 mole fraction of acenaphthene. Furthermore, the activity coefficients of the components in the binary mixtures have been correlated by the Scatchard–Hildebrand expression with one adjustable parameter. This approach offers a useful procedure for estimating with good accuracy.     

Formation of active phases of Fe/C,Cr/C and Fe–Cr/C catalysts in oxidative dehydrogenation of ethane

The oxidative dehydrogenation of ethane into ethylene using CO₂ as an oxidant at temperatures of 650–750 °C was carried out over Fe/C, Cr/C and Fe–Cr/C catalysts deposited on a carbon support. Before and after the reaction the catalysts were investigated by X-ray powder diffraction (XRD), in situ magnetometry and transmission electron microscopy methods. The correlation between activity of Fe/C, Cr/C and Fe–Cr/C catalytic systems and their phase composition was established.     

Application of the Intramolecular α-Amido-alkylation Reaction for the Synthesis of Dibenzo /a,h/ Quinolizines

5,6,9-Trihydro-8H-dibenzo [a,h] quinolizin-8-ones 6 are obtained from adducts of 3,4-dihydroiso-quinolines 1 and phenylacetyl chlorides as a result of an intramolecular α-amidoalkylation reaction.     

Characterization of PDZ domain–peptide interactions using an integrated protocol of QM/MM,PB/SA,and CFEA analyses

Protein–protein interactions, particularly weak and transient ones, are often mediated by peptide recognition domains. Characterizing the interaction interface of domain–peptide complexes and analyzing binding specificity for modular domains are critical for deciphering protein–protein interaction networks. In this article, we report the successful use of an integrated computational protocol to dissect the energetic profile and structural basis of peptide binding to third PDZ domain (PDZ3) from the PSD-95 protein. This protocol employs rigorous quantum mechanics/molecular mechanics (QM/MM), semi-empirical Poisson–Boltzmann/surface area (PB/SA), and empirical conformational free energy analysis (CFEA) to quantitatively describe and decompose systematic energy changes arising from, respectively, noncovalent interaction, desolvation effect, and conformational entropy loss associated with the formation of 30 affinity-known PDZ3–peptide complexes. We show that the QM/MM-, PB/SA-, and CFEA-derived energy components can work together fairly well in reproducing experimentally measured affinity after a linearly weighting treatment, albeit they are not compatible with each other directly. We also demonstrate that: (1) noncovalent interaction and desolvation effect donate, respectively, stability and specificity to complex architecture, while entropy loss contributes modestly to binding; (2) P₀ and P₋₂ of peptide ligand are the most important positions for determining both the stability and specificity of the PDZ3–peptide complex, P₋₁ and P₋₃ can confer substantial stability (but not specificity) for the complex, and N-terminal P₋₄ and P₋₅ have only a very limited effect on binding.     

XPS study of nanorods of doped vanadium oxide MxV2O5 · nH2O (M = Na, K, Rb, Cs)

Nanorods of vanadium oxide doped with alkali metal ions M _x V₂O₅ · nH₂O (M = Na, K, Rb, Cs, x = 0.31–0.44) have been obtained under hydrothermal conditions. The particles are 30–80 nm in diameter and a few micrometers in length. The chemical state of atoms and their concentration ratios have been studied by XPS. It has been shown that vanadium atoms are in two oxidation states V⁵⁺ and V⁴⁺ and the concentration of vanadium(IV) ions directly depends on the alkali metal. The X-ray photoelectron spectra of the valence bands of M _x V₂O₅ · nH₂O (M = Na, K, Rb, Cs) nanorods have been measured and interpreted.     

One pot synthesis of α,α-bis(N-arylamido) lactams via iodide-catalyzed rearrangement of β,β-bis(N-arylamido) cyclic ketene-N,O-acetals

Five and six-membered cyclic ketene-N,O-acetals, generated in situ from 2,3-dimethyl-2-oxazolinium iodide or 2,3-dimethyl-2-oxazinium iodide and triethylamine, reacted with aryl isocyanates in refluxing THF producing α,α-bis(N-arylamido) lactams via the iodide-catalyzed rearrangement of β,β-bis(N-arylamido) cyclic ketene-N,O-acetal intermediates. The cyclic ketene-N,O-acetal generated in situ from 2,3,4,4-tetramethyl-2-oxazolinium iodide reacted with isocyanates to give β,β-bis(N-arylamido) cyclic ketene-N,O-acetals, which do not readily rearrange. The two methyls at C-4 hindered the nucleophilic attack of iodide on C-5, which is required for rearrangement.     

Synthesis of 2,3-disubstituted benzofurans and indoles by π-Lewis acidic transition metal-catalyzed cyclization of ortho-alkynylphenyl O,O- and N,O-acetals

The PtCl₂-catalyzed cyclization reaction of ortho-alkynylphenyl acetals 1 in the presence of COD (1,5-cyclooctadiene) produces 3-(α-alkoxyalkyl)benzofurans 2 in good to high yields. For example, the reaction of acetaldehyde ethyl 2-(1-octynyl)phenyl acetal (1a), acetaldehyde ethyl 2-(cyclohexylethynyl)phenyl acetal (1c), and acetaldehyde ethyl 2-(phenylethynyl)phenyl acetal (1f) in the presence of 2 mol % of platinum(II) chloride and 8 mol % of 1,5-cycloocatadiene in toluene at 30 °C gave the corresponding 2,3-disubstituted benzofurans 2a, 2c, and 2f in 91, 94, and 88% yields, respectively. Moreover, the reaction of N-methoxymethyl-2-alkynylanilines 3 was catalyzed by PdBr₂, affording the corresponding 2,3-disubstituted indoles 4 in moderate yields. For example, the reaction of N-methoxymethyl-2-(1-pentynyl)-N-tosylaniline (3a) and N-methoxymethyl-2-(phenylethynyl)-N-tosylaniline (3b) in the presence of 10 mol % of PdBr₂ in toluene at 80 °C gave 3-methoxymethyl-2-propyl-1-tosylindole (4a) and 3-methoxymethyl-2-phenyl-1-tosylindole (4b) in 33 and 33% yields, respectively.     

Influence of the basis set on the calculation of the absolute 13C shieldings of methyl derivatives (CH3X with X?=?CH3, CN, NH2, NO2, OH, F) with special emphasis in the cases of X?=?Cl, Br, SH, SeH, and PH2

A theoretical B3LYP/6-311++G(d,p) study of four derivatives of cyclooctadiene bearing two aromatic or heteroaromatic rings is reported. The conformational analysis reproduces well the experimental results (minima and transition states). The GIAO calculated ¹H and ¹³C chemical shifts proved useful in solving some stereochemical questions.     

Vibrational spectra of N,N-dimethyl/diethylaniline,N,N,N′,N′-tetramethyl/tetraethyl-p-phenylenediamine and N,N,N′,N′-tetramethyl/tetraethylbenzidine derivatives

The ground state and protonated state (quaternized salt) vibrational spectra (200–1800 cm⁻¹) of the title amines are reported for various ring and/or methyl deuterated derivatives. Complete assignments are proposed and compared to those established for the parent hydrocarbons, benzene and biphenyl, and for the parent primary amines, aniline, p-phenylenediamine and benzidine. The electronic distribution, N(n)→ring(π) charge-transfer character and inductive effects are characterized from a vibrational point of view. Finally changes in the vibrational and electronic conformation upon protonation of the nitrogen atom are discussed. These results provide a fundamental basis for the vibrational investigation of excited states and reactive transients of aromatic amines.     

Comparison of the spectroscopic properties of π-conjugated, fused salphen triads embedded with Zn-homo-, Ni-homo-, and Ni/Zn-heteronuclei

Stepwise condensation reactions of 2,6-dihydroxynaphthalene-1,5-dicarbaldehyde and a phenylenediamine with concomitant binding of metal ions afforded a trinuclear complex of a fully π-conjugated, fused salphen ligand. By changing the synthetic pathway, we obtained a series of homo- and heteronuclear complexes containing selected combinations of nickel(II) and zinc(II) ions. Comparison of the trinuclear complexes' spectroscopic features with those of analogous dinuclear complexes revealed that the absorption spectrum of each trinuclear complex is composed of a salphen-centered absorption at 400 nm and a naphthalene-centered absorption around 500-600 nm, suggesting that the π-conjugated system is divided into several compartments, each of which independently undergoes electronic excitation. Molecular orbital calculations revealed that the formal fusion of the salphen moieties increases the highest occupied molecular orbital (HOMO) level by ～0.4 eV, which in turn causes the low-energy absorption observed in the spectra. In contrast, interorbital interactions mediated by the N(2)O(2) metal coordination site are small, even though this site is bridged by an o-phenylene linkage. These results suggest that the coordination site effectively breaks electronic communication between the compartments, which in turn affect various spectroscopic properties of the π-conjugated metallo-polysalphens.     

Synthesis, characterization, and norbornene polymerization of η-benzylnickel(II) complexes of N-heterocyclic carbenes

Neutral η¹-benzylnickel carbene complexes, [Ni(η¹-CH₂C₆H₅)(IiPr)(PMe₃)(Cl)] (3) (IiPr = 1,3-bis-(2,6-diisopropylphenyl)imidazol-2-ylidene) and [Ni(η¹-CH₂C₆H₅)(SIiPr)(PMe₃)(Cl)] (4) (SIiPr = 1,3-bis-(2,6-diisopropylphenyl)imidazolin-2-ylidene), were prepared by the reaction between [Ni(η³-CH₂C₆H₅)(PMe₃)(Cl)] and an equivalent amount of the corresponding free N-heterocyclic carbene. The preparation of η³-benzylnickel carbene complexes, [Ni(η³-CH₂C₆H₅)(IiPr)(Cl)] (5) and [Ni(η³-CH₂C₆H₅)(SIiPr)(Cl)] (6) were carried out by the abstraction of PMe₃ from 3 and 4 by the treatment of B(C₆F₅)₃. The treatment of AgX on 5 and 6 produced the anion-exchanged complexes, [Ni(η³-CH₂C₆H₅)(NHC)(X)] (7, NHC = IiPr, X = O₂CCF₃; 8, NHC = IiPr, X = O₃SCF₃; 9, NHC = SIiPr, X = O₂CCF₃; 10, NHC = SIiPr, X = O₃SCF₃). The solid state structures of 3 and 10 were determined by X-ray crystallography. The η³-benzyl complexes of IiPr (5, 7, and 8) alone, in the absence of any activators such as borate and MAO, showed good catalytic activity towards the vinyl-type norbornene polymerization. The catalyst was thermally robust and the activity increases as the temperature rises to 130 °C.     

The phase diagram and tetragonal superstructures of the rare earth cobaltate phases Ln1−xSrxCoO3-δ (Ln=La, Pr, Nd, Sm, Gd, Y, Ho, Dy, Er, Tm and Yb)

Single phase perovskite-based rare earth cobaltates (Ln_1−xSr_xCoO_3−δ) (Ln=La³⁺, Pr³⁺, Nd³⁺, Sm³⁺, Gd³⁺, Dy³⁺, Y³⁺, Ho³⁺, Er³⁺, Tm³⁺ and Yb³⁺; 0.67?x?0.9) have been synthesized at 1100°C under 1 atmosphere of oxygen. X-ray diffraction of phases containing the larger rare earth ions La³⁺, Pr³⁺ and Nd³⁺ reveals simple cubic structures; however electron diffraction shows orientational twinning of a local, tetragonal (I4/mmm; a_p×a_p×2a_p) superstructure phase. Orientational twinning is also present for Ln_1−xSr_xCoO_3−δ compounds containing rare earth ions smaller than Nd³⁺. These compounds show a modulated intermediate parent with a tetragonal superstructure (I4/mmm; 2a_p×2a_p×4a_p). Thermogravimetric measurements have determined the overall oxygen content, and these phases show mixed valence (3⁺/4⁺) cobalt oxidation states with up to 50% Co(IV). X-ray diffraction data and Rietveld techniques have been used to refine the structures of each of these tetragonal superstructure phases (Ln=Sm³⁺-Yb³⁺). Coupled Ln/Sr and oxygen/vacancy ordering and associated structural relaxation are shown to be responsible for the observed superstructure.     

Spectroscopic Parameters of X3∑-, a1△, and A'3△ Electronic States of SO Radical

The potential energy curves (PECs) of three low-lying electronic states (X³∑^-, a¹△, and A^'3△) of SO radical have been studied by ab initio quantum chemical method. The calcula-tions were carried out with the full valence complete active space self-consistent field method followed by the highly accurate valence internally contracted multireference configuration in-teraction (MRCI) approach in combination with correlation-consistent basis sets. Effects of the core-valence correlation and relativistic corrections on the PECs are taken into account. The core-valence correlation correction is carried out with the cc-pCVDZ basis set. The way to consider the relativistic correction is to use the second-order Douglas-Kroll Hamiltonian approximation, and the correction is performed at the level of cc-pV5Z basis set. To obtain more reliable results, the PECs determined by the MRCI calculations are also corrected for size-extensivity errors by means of the Davidson modification (MRCI+Q). These PECs are extrapolated to the complete basis set limit by the two-point energy extrapolation scheme. With these PECs, the spectroscopic parameters are determined.     

Total synthesis of apigenin 7,4′-di-O-β-glucopyranoside, a component of blue flower pigment of Salvia patens, and seven chiral analogues

We have succeeded in the first total synthesis of apigenin 7,4′-di-O-β-d-glucopyranoside (1a), a component of blue pigment, protodelphin, from naringenin (2). Glycosylation of 2 according to Koenigs-Knorr reaction provided a monoglucoside 4a in 80% yield, and this was followed by DDQ oxidation to give apigenin 7-O-glucoside (12a). Further glycosylation of 4′-OH of 12a with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl fluoride (5a) was achieved using a Lewis acid-and-base promotion system (BF₃·Et₂O, 2,6-di-tert-butyl-4-methylpyridine, and 1,1,3,3-tetramethylguanidine) in 70% yield, and subsequent deprotection produced 1a. Synthesis of three other chiral isomers of 1a, with replacement of d-glucose at 7 and/or 4′-OH by l-glucose (1b-d), and four chiral isomers of apigenin 7-O-β-glucosides (6a,b) and 4′-O-β-glucosides (7a,b) also proved possible.     

N-Heterocyclic carbene-catalyzed dehydration of α,ω-disilanol oligomers

An efficient polycondensation reaction of α,ω-dihydroxy oligodimethylsiloxanes, catalyzed by N-heterocyclic carbenes (NHC), is developed for the first time. Surprisingly, in this polymerization, the moisture sensitive NHC catalyze the dehydration of disilanol oligomers, and remains intact. This result demonstrates the compatibility of NHCs with the intervention of H₂O in catalytic reactions.     

Degree of order and redox balance in B-site ordered double-perovskite oxides, Sr2MMoO6−δ (M=Mg, Mn, Fe, Co, Ni, Zn)

We have investigated a series of double-perovskite oxides Sr₂MMoO_6−δ (M=Mg, Mn, Fe, Co, Ni, Zn) for redox stability, oxygen content and crystal structure. Phases with M=Co, Ni and Zn were found to be oxygen-stoichiometric and stable under oxidizing conditions, whereas those with M=Mn and Fe were oxygen-deficient and stable under reducing conditions. The M=Mg phase is stable both under reducing and oxidizing conditions, showing variable oxygen contents within 0.00≤δ≤0.04 depending on the annealing conditions. Structural data indicate somewhat depressed values for the degree of M/Mo cation order and also evidence of electron transfer from M^II to Mo^VI for M=Mn, Fe and Co.     

Bromophilic substitution/carbophilic substitution cascade reactions of α,α-dibromo-2-methoxyacetophenone with C-, N- and O-nucleophiles

α,α-Dibromo-2-methoxyacetophenone reacts, under mild reaction conditions, with C-, N- and O-nucleophiles via a bromophilic substitution/protonation/carbophilic substitution cascade process to afford α-monosubstituted-2-methoxyacetophenones in moderate to good yield. The only exception from this reaction pathway is the reaction with the anion derived from malononitrile in which 2-aroyl-1,1,3,3-tetracyanopropene is obtained.