Trace determination of gadolinium in biomedical samples by diode laser-based multi-step resonance ionization mass spectrometry

The application of high-resolution multi-step resonance ionization mass spectrometry (RIMS) to the trace determination of the rare earth element gadolinium is described. Utilizing three-step resonant excitation into an autoionizing level, both isobaric and isotopic selectivity of >10(7) were attained. An overall detection efficiency of approximately 10(-7) and an isotope specific detection limit of 1.5 x 10(9) atoms have been demonstrated. When targeting the major isotope (158)Gd, this corresponds to a total Gd detection limit of 1.6 pg. Additionally, linear response has been demonstrated over a dynamic range of six orders of magnitude. The method has been used to determine the Gd content in various normal and tumor tissue samples, taken from a laboratory mouse shortly after injection of gadolinium diethylenetriaminepentaacetic acid dimeglumine (Gd-DTPA), which is used as a contrast agent for magnetic resonance imaging (MRI). The RIMS results show Gd concentrations that vary by more than two orders of magnitude (0.07-11.5 microg mL(-1)) depending on the tissue type. This variability is similar to that observed in MRI scans that depict Gd-DTPA content in the mouse prior to dissection, and illustrates the potential for quantitative trace analysis in microsamples of biomedical materials.     

Determination of carvedilol in human cardiac tissue by high-performance liquid chromatography

A new high-performance liquid chromatographic method has been developed for the determination of the beta-receptor blocker carvedilol in human cardiac tissue. After homogenizing tissue samples in a microdismembrator, carvedilol and the internal standard naftopidil are extracted with acetone. The extract is evaporated to dryness and reconstituted in a potassium acetate buffer of pH 3.5. Samples are cleaned up with solid-phase extraction columns. Carvedilol and the internal standard show recoveries of 69.8 +/- 12.2% and 63.9 +/- 9.34%, respectively. The linearity range for carvedilol is 0.01-0.35 ng/mg (parts per billion) tissue (wet weight), and the limit of quantitation is 0.01 ng/mg. The percentage coefficient of variation of the intra-assay varies between 1.45 and 5.38% and the interassay between 4.25 and 6.96%. To use as an application of the assay, the cardiac carvedilol tissue level in a patient on oral carvedilol therapy for congestive heart failure is reported.     

Synthesis and properties of niobia films derived from niobium pentaethoxide

The hydrolysis of niobium pentaethoxide precursor in the presence of triethylamine (TEA) is discussed. Three precursors with TEA/Nb(OEt)₅ mole ratios of 0.25, 0.4 and 0.8 were prepared. Niobia colloids with different appearance were obtained after autoclaving the above precursors at 250°C during 12 h. The surface roughness and microstructure of niobia films prepared with the colloids by spread coating method are strongly dependent on the TEA/Nb(OEt)₅ mole ratio. At a value of 0.4 TEA/Nb(OEt)₅ mole ratio, a niobia film with large surface roughness can be achieved. It is opaque and mechanically stable and has differently ordered needle microstructure. The crystalline structure and photoelectrochemical property of niobia film with the largest surface roughness were examined. The effect of CO₂ gas bubbling, reflux and addition of 2-methoxyethanol on the hydrolysis of Nb(OEt)₅ and the nature of the Nb₂O₅ films is also discussed.     

Microwave-assisted "libraries from libraries" approach toward the synthesis of allyl- and C-cyclopropylalkylamides

Cascade reactions of internal and terminal alkynes, zirconocene hydrochloride, dimethylzinc, and phosphinoyl imines (prepared in one step from aldehydes and diphenylphosphinoyl amide) lead to allylic phosphinoyl amides after aqueous workup. Microwave acceleration allows the completion of this one-pot reaction sequence in 10 min. These allylic amides can be converted into a variety of derivatives, including carbamates and sulfonamides, or reacted prior to workup with diiodomethane to give novel C-cyclopropylalkylamides. A solution-phase "libraries from libraries" approach was used to generate an intermediate 20-member library which was subsequently expanded to a 100-member library by a series of N-functionalizations. The biological activity was evaluated in an assay for competitive binding to the estrogen receptor (ERalpha), revealing three potent lead compounds of a new structural type.     

Heterologous expression and characterization of recombinant phytochrome from the green alga Mougeotia scalaris

The full-length apoprotein (124 kDa) and the chromophore-binding N-terminal half (66 kDa) of the phytochrome of the unicellular green alga Mougeotia scalaris have been heterologously expressed in the methylotrophic yeast Pichia pastoris. Assembly with the tetrapyrrole phycocyanobilin (PCB) yielded absorption maxima (for the full-length protein) at 646 and 720 nm for red- and far-red absorbing forms of phytochrome (Pr and Pfr), respectively, whereas the maxima of the N-terminal 66 kDa domain are slightly blueshifted (639 and 714 nm, Pr and Pfr, respectively). Comparison with an action spectrum reported earlier gives evidence that in Mougeotia, as formerly reported for the green alga Mesotaenium caldariorum, PCB constitutes the genuine chromophore. The full-length protein, when converted into its Pfr form and kept in the dark, reverted rapidly into the Pr form (lifetimes of 1 and 24 min, ambient temperature), whereas the truncated chromopeptide (66 kDa construct) was more stable and converted into Pr with time constants of 18 and 250 min. Also, time-resolved analysis of the light-induced Pfr formation revealed clear differences between both recombinant chromoproteins in the various steps involved. The full-length phytochrome showed slower kinetics in the long milliseconds-to-seconds time domain (with dominant Pfr formation processes of ca 130 and 800 ms), whereas for the truncated phytochrome the major component of Pfr formation had a lifetime of 32 ms.     

Molecular structure of t-butyl-phenylphosphinic acid (−)-menthyl ester: a comparison of solid state and solution

The molecular structure of t-butyl-phenylphosphinic acid (?)-menthyl ester (1eS) has been determined by X-ray analysis and the results compared with the findings of a detailed NMR-study. 1eS crystallises in the monoclinic space group P2 ₁ with a = 9.304(2), b = 10.678(4), c = 12.681(4) Å, β = 124.91(1)°, Z = 2, D_x = 1.08 g cm^?3. The structure was refined to R = 0.035 for 1842 independent reflections. The absolute configuration was confirmed as S_(p). Both methyl functions of the menthyl-iso-propyl substituent take up positions close to the phenyl ring system.     

Metallacycloalkanes: I. Preparation and characterisation of α,α′-bipyridyl-5-nickela-3,3,7,7-tetramethyl-trans-tricyclo[4.1.0.02,4]heptane

Oxidative addition of 2 molecules of 3,3-dimethylcyclopropene (I) to α,α′-bipyridyl(1,5-cyclooctadiene)nickel(0) (III) gave the title compound (IV) in over 90% yield. Complex IV was characterized by mass, ¹H NMR and ¹³C NMR spectroscopy. Its structure was determined by X-ray diffraction (a 13.7081(2), b 14.638(2), c 9.5139(1) Å, β 110.82(1)°, C2/c, R = 0.05 for 1614 reflections).     

Mechanisms for the solvolytic decompositions of nucleoside analogues—I: Acidic hydrolysis of 2-substituted 1-(1-ethoxyethyl)benzimidazoles

A few 2-substituted 1-(1-ethoxyethyl)benzimidazoles have been prepared and the rate constants for their hydrolysis measured at various temperatures and oxonium ion concentrations. The formal kinetics followed and the effect of varying the 2-substitution on the hydrolysis rate suggest that the acid-catalyzed cleavage of these compounds involves a rapid initial protonation of the benzimidazole ring and a subsequent rate-limiting heterolysis of the protonated substrate to form a free nitrogen base and an ocarbenium ion derived from the ethoxyethyl group. The values obtained for the entropy of activation are consistent with the assumed unimolecular nature of the rate-limiting step. The effects of 2-substituents on the acidities of the protonated substrates and their heterolysis rates have been compared. The latter partial reaction has been suggested to be the subject of steric acceleration.     

Eliminative deoxygenation: the facile formation of α-trimethylsilyl vinyl sulfides from sulfoxides

Synthetically useful α-trimethylsilyl vinyl sulfides are generated in high yields by deoxygenation of the corresponding sulfoxides in the presence of excess LDA and trimethylsilyl chloride.     

Eliminative deoxygenation: A facile synthesis of α-cyano and α-carboalkoxy substituted vinyl sulfides

The faciIe eliminative deoxygenation of α-cyano and carboalkoxy sulfoxides by trimethylsilyl triflate under mildly basic conditions results in the formation of α-thiophenyl substituted α,β-unsaturated nitriles and esters in high yields.