Determination of 19-norandrosterone in CCQM-P68. NIST results using an isotope dilution liquid chromatography/tandem mass spectrometry method

The US National Institute of Standards and Technology (NIST) participated in an international interlaboratory study under the auspices of the Consultative Committee for Amount of Substance (CCQM) for the determination of 19-norandrosterone (19-NA) in urine, the principal metabolite of nandrolone and certain other synthetic testosterone substitutes banned for use by the World Antidoping Agency (WADA). Prior to this study, NIST developed a candidate reference measurement procedure based upon isotope dilution liquid chromatography/tandem mass spectrometry. This method was applied to a urine sample distributed to the participants in the study by the Australian National Measurement Institute, Pymble, Australia (NMIA). The NIST results were in very good agreement with those from the other participants, all of whom used methods based upon gas chromatography/mass spectrometry. All known significant sources of uncertainty were evaluated, resulting in a relative expanded uncertainty of less than 5% (coverage factor k = 2).     

Sphericities of Double Cosets,Double Coset Representations,and Fujita’s Proligand Method for Combinatorial Enumeration of Stereoisomers

The concepts of double coset representations and sphericities of double cosets are proposed to characterize stereoisomerism, where double cosets are classified into three types, i.e., homospheric double cosets, enantiospheric double cosets, or hemispheric double cosets. They determine modes of substitutions (i.e., chirality fittingness), where homospheric double cosets permit achiral ligands only; enantiospheric ones permit achiral ligands or enantiomeric pairs; and hemispheric ones permit achiral and chiral ligands. The sphericities of double cosets are linked to the sphericities of cycles which are ascribed to right coset representations. Thus, each cycle is assigned to the corresponding sphericity index (a _d , c _d , or b _d ) so as to construct a cycle indices with chirality fittingness (CI-CFs). The resulting CI-CFs are proved to be identical with CI-CFs introduced in Fujita’s proligand method (S. Fujita, Theor. Chem. Acc. 113 (2005) 73–79 and 80–86). The versatility of the CI-CFs in combinatorial enumeration of stereoisomers is demonstrated by using methane derivatives as examples, where the numbers of achiral plus chiral stereoisomers, those of achiral stereoisomers, and those of chiral stereoisomers are calculated separately by means of respective generating functions.     

Adsorption and structure formation of the weak polyelectrolytic diblock copolymer,PVP-<Emphasis Type="Italic">b</Emphasis>-PDMAEMA

This paper reports on the pH-dependent adsorption of weak the polyelectrolytic diblock copolymer poly(2-vinylpyridine)-block-poly(dimethylaminoethyl methacrylate), (PVP-b-PDMAEMA). Aqueous PVP-b-PDMAEMA solutions have been adsorbed on alkaline pretreated silicon substrates. Altogether two copolymers differing in block ratio and molecular weight were used for the investigations. While the electrical charge of both samples in solution was investigated by electrophoretic measurements, the adsorbed polymer layers were studied with ellipsometry and atomic force microscopy (AFM). Depending on pH the electrical charge of both blocks of the diblock copolymer varied. Three different regimes have been identified. Under acidic conditions at pH<5, both blocks are mainly positively charged. At medium pH between 5 and 8, only the PDMAEMA block is positively charged. At pH>8, both blocks are nearly uncharged and a polymer precipitation occurred in solution. Each of these pH regimes was characterized by a specific adsorption behaviour leading to two adsorption maxima at acidic and alkaline pH values, while at medium pH a plateau in the adsorbed amount was observed. Moreover, the structures of the polyelectrolytes formed on the substrate after adsorption were specific to each of the three pH regimes.     

Synthesis,structure, and thermal decomposition of a novel one-dimensional chain complex of manganese(II) with 2,2-diphenic acid and 1,10-phenanthroline

A novel one-dimensional (1D) chain coordination polymer [Mn₂(2,2′-dipha)₂(phen)]_n has been synthesized by hydrothermal reaction, and characterized by elemental analysis, IR spectroscopy, TGA, and X-ray diffraction. Orange crystals crystallized in the monoclinic system, space group C2/c with a = 19.393(7) Å, b = 19.183(7) Å, c = 19.729(7) Å, β = 90.826(6)°, V = 7338(5) ų, Z = 8. In the crystal structure, one manganese atom is six-coordinated with four carboxylate oxygen atoms from one pentadentate 2,2′-dipha ligand and two tetradentate 2,2′-dipha ligands, and with two nitrogen atoms of one phen ligand, giving a slightly distorted octahedral geometry. The other manganese atom is five-coordinated with five oxygen atoms from two tetradentate 2,2′-dipha ligands and two pentadentate 2,2′-dipha ligands and has a trigonal bipyramidal environment. The TGA curve shows that the compound is stable below 310°.     

Swelling behavior of ionically cross-linked polyampholytic hydrogels in varied salt solutions

Ionically cross-linked polyampholytic hydrogels were synthesized by redox copolymerization of acrylamide and an ionic complex of (N,N-diethylamino)ethyl methacrylate and acrylic acid (designated as PADA hydrogel). The swelling behavior of the hydrogels in water indicated that a minimal equilibrium swelling ratio is found when the molar ratio of anionic/cationic monomers was 1.55. In NaCl solution, the hydrogels exhibited the typical swelling behavior of conventional polyampholytic gels. Their equilibrium swelling ratios increased with an increase in the NaCl concentration. In solutions of multivalent ions (CaCl₂ and trisodium citrate solutions), the equilibrium swelling ratios of the hydrogels increased first and were then followed by a decrease with an increase in salt concentration. Interestingly, an unexpected abrupt swelling phenomenon was observed when the fully swollen hydrogels in salt solution were transmitted to pure water. The unique swelling behavior of PADA hydrogels depends not only on the molar ratio of the anionic/cationic monomers but also on the valency of the ions.     

Reactivity of organolanthanide and organolithium complexes containing the guanidinate ligands toward isocyanate or carbodiimide: synthesis and crystal structures

The direct reactions of (C5H5)2LnCl with LiN=C(NMe2)2 proceeded at room temperature in THF under pure nitrogen to yield the lanthanocene guanidinate complexes [(C5H5)2Ln(mu-eta1:eta2-N=C(NMe2)2)]2 (Ln = Gd (1), Er (2)). Treatment of phenyl isocyanate with complexes 1 and 2 results in monoinsertion of phenyl isocyanate into the Ln-N(mu-Gua) bond to yield the corresponding insertion products [(C5H5)2Ln(mu-eta1:eta2-OC(N=C(NMe2)2)NPh)]2 (Ln = Gd (3), Er (4)), presenting the first example of unsaturated organic small molecule insertion into the metal-guanidinate ligand bond. Further investigations indicate that N,N'-diisopropylcarbodiimide does not react with complexes 1 and 2 under the same conditions; however, it readily inserts into the lithium-guanidinate ligand bond of LiN=C(NMe2)2. As a synthon of the insertion product Li[(iPrN)2C(N=C(NMe2)2)], its reaction with (C5H5)2LnCl gives the novel organolanthanide complexes containing the guanidinoacetamidinate ligand, (C5H5)2Ln[(iPrN)2C(N=C(NMe2)2)] (Ln = Yb (5), Er (6), Dy (7)). All complexes were characterized by elemental analysis and spectroscopic properties. The structures of complexes 1, 3, 5 and 7 were determined through X-ray single-crystal diffraction analysis.     

SARS-CoV protease inhibitors design using virtual screening method from natural products libraries

Two natural products databases, the marine natural products database (MNPD) and the traditional Chinese medicines database (TCMD), were used to find novel structures of potent SARS-CoV protease inhibitors through virtual screening. Before the procedure, the databases were filtered by Lipinski's ROF and Xu's extension rules. The results were analyzed by statistic methods to eliminate the bias in target-based database screening toward higher molecular weight compounds for enhancing the hit rate. Eighteen lead compounds were recommended by the screening procedure. They were useful for experimental scientists in prioritizing drug candidates and studying the interaction mechanism. The binding mechanism was also analyzed between the best screening compound and the SARS protein.     

Intramolecular cyclization of 5-aryl-3-arylamino-4-benzoyl-1h-3-pyrrolin-2-ones to pyrrolo[3,4-<Emphasis Type="Italic">b</Emphasis>]quinolines

It has been shown that 5-aryl-3-arylamino-4-benzoyl-1H-3-pyrrolin-2-ones cyclize in the presence of conc. H₂SO₄ to give pyrrolo[3,4-b]quinolines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1543–1545, October, 2004.     

Comparison of the fragility index of different eudragit polymers determined by activation enthalpies

The present study aimed to apply fragility index (m) of polymers in the determination of the optimal amount of plasticizer in polymer films. The fragility index of different Eudragit polymers (RS, RL, EPO) was assessed by differential scanning calorimerty (DSC), applying the Arrhenius connection (logq–1/T _g). The fragility of Eudragit EPO films proved to be the highest, while in the case of RS and RL, the increase of the alkyl-chain length caused the increase of fragility. Studying the effect of plasticizer (triethyl citrate, TEC) on the m value of Eudragit RL and RS films, a near linear reduction of the fragility index could be observed between 5–30% TEC concentration, but above 30%, this value leveled out to constant.     

Human immunoglobulin adsorption investigated by means of quartz crystal microbalance dissipation, atomic force microscopy, surface acoustic wave, and surface plasmon resonance techniques

Time-resolved adsorption behavior of a human immunoglobin G (hIgG) protein on a hydrophobized gold surface is investigated using multitechniques: quartz crystal microbalance/dissipation (QCM-D) technique; combined surface plasmon resonance (SPR) and Love mode surface acoustic wave (SAW) technique; combined QCM-D and atomic force microscopy (AFM) technique. The adsorbed hIgG forms interfacial structures varying in organization from a submonolayer to a multilayer. An "end-on" IgG orientation in the monolayer film, associated with the surface coverage results, does not corroborate with the effective protein thickness determined from SPR/SAW measurements. This inconsistence is interpreted by a deformation effect induced by conformation change. This conformation change is confirmed by QCM-D measurement. Combined SPR/SAW measurements suggest that the adsorbed protein barely contains water after extended contact with the hydrophobic surface. This limited interfacial hydration also contributed to a continuous conformation change in the adsorbed protein layer. The viscoelastic variation associated with interfacial conformation changes induces about 1.5 times overestimation of the mass uptake in the QCM-D measurements. The merit of combined multitechnique measurements is demonstrated.